Skip to main content
Log in

Bromodeoxyuridine: a diagnostic tool in biology and medicine, Part I: Historical perspectives, histochemical methods and cell kinetics

  • Review
  • Published:
The Histochemical Journal Aims and scope Submit manuscript

Summary

Bromodeoxyuridine (BrdUrd), a thymidine analogue incorporated into DNA, can be quantified by fluorescent or chromophoric quenching of dyes bound to DNA or with antibodies to BrdUrd. These technologies have been used since the 1970s as tools for measuring DNA synthesis in isolated chromosomes and in cells and tissues. This paper is Part I of a three-part comprehensive review of the literature over the last 20 years (to the end of 1993) describing the histochemical methods for measuring BrdUrd in cells and tissues. Fixation, denaturation and staining procedures are compared for quantifying BrdUrd for microscopy and flow cytometry. Non-immunochemical methods related to the quenching of fluorescent DNA stains by BrdUrd are also described. Methods are described for the comparative assay of cell kinetic parameters by tritiated thymidine and bromodeoxyuridine. The multivariate BrdUrd/DNA assay of Ts, and Tc, and a comparison of recent methods based on the single biopsy bivariate analysis of Tpot, is presented. Recent developments in the use of double halopyrimidine label to determine kinetic parameters are also reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aarnaes,E.,Kirkhus,B. &Clausen,O. P. (1990) Mathematical model analysis of mouse epidermal cell kinetics measured by bivariate DNA/anti-bromodeoxyuridine flow cytometry and continuous [3H]-thymidine labelling.Cell Tissue Kinet. 23, 409–24.

    CAS  PubMed  Google Scholar 

  • Aarnaes,E.,Clausen,O. P.,Kirkhus,B. &De,Angelis,P. (1993) Heterogeneity in the mouse epidermal cell cycle analysed by computer simulations.Cell Prolif. 26, 205–19.

    CAS  PubMed  Google Scholar 

  • Alberts,B.,Bray,D.,Lewis,J.,Raff,M.,Roberts,K. &Watson,J. (1983)Molecular Biology of the Cell. pp. 424–6. New York: Garland Publishing.

    Google Scholar 

  • Apte,S. S. (1990a) Ki67 monoclonal antibody (MAb) reacts with a proliferation associated nuclear antigen in the rabbitOryctolagus cuniculus.Histochemistry 94, 201–4.

    CAS  PubMed  Google Scholar 

  • Apte,S. S. (1990b) Validation of bromode-oxyuridine immunohistochemistry for localization of S-phase cells in decalcified tissues. A comparative study with tritiated thymidine autoradiography.Histochem. J. 22, 401–8.

    Article  CAS  PubMed  Google Scholar 

  • Apte,S. S. &Puddle,B. (1990) Bromodeoxyuridine (BrdUrd) immunohistochemistry in undecalcified plastic-embedded tissue. Elimination of the DNA denaturation step.Histochemistry 93, 631–5.

    Article  CAS  PubMed  Google Scholar 

  • Ardito,G.,Lamberti,L.,Stanyon,R. &Benedetti,G. (1981) Cellular kinetics in lymphocytes of 4 species of macaques measured by BRDU sister-chromatid differential staining.Mutat. Res. 91, 141–6.

    Article  CAS  PubMed  Google Scholar 

  • Aten,J. A.,Barker,P. J. M.,Stap,J.,Boschman,G. A. &Veenhof,C. H. N. (1992) DNA double labelling with IdUrd and CldUrd for spatial and temporal analysis of cell proliferation.Histochem. J. 24, 251–9.

    Article  CAS  PubMed  Google Scholar 

  • Awwad,H. K. (1992) Unconventional fractionation studies and Tpot correlation.Sem. Radiat. Oncol. 2, 62–6.

    Google Scholar 

  • Barkker,P. J. M.,Tukker,C. J.,VanOven,C. H.,Veenhof,C. H. N. &Aten,J. (1991) An indirect immunofluorescent staining procedure for the simultaneous flow cytometric measurement of iodo-and chlorodeoxyuridine incorporated into DNA.Cytometry 12, 366–72.

    Google Scholar 

  • Bardenstein,D. S.,Char,D. H.,Kaleta-Michaels,S. &Kroll,S. M. (1991) Ki67 and bromodeoxyuridine labelling of human choroidal melanoma cells.Curr. Eye Res. 10, 479–84.

    CAS  PubMed  Google Scholar 

  • Bauer,K. D.,Merkel,D. E.,Winter,J. N.,Marder,R. J.,Hauck,W. W.,Wallemark,C. B.,Williams,T. J. &Variakojis,D. (1986) Prognostic implications of ploidy and proliferative activity in diffuse large cell lymphomas.Cancer Res. 46, 3173–8.

    CAS  PubMed  Google Scholar 

  • Bayer,J. A.,DeVries,P.,Herweijer,H. &Bauman,J. G. (1990) The use of E. coli exonuclease III to generate single stranded DNA in BrdUrd cell-cycle analysis permits simultaneous detection of cell surface antigens.J. Immunol. Meth. 132, 13–24.

    Article  CAS  Google Scholar 

  • Beauregard,P.,Witzig,T. E.,Kurtin,P. J.,Greipp,P. R.,Stenson,M. J.,Katzmann,J. A.,Haber-Mann,T. M. &Wieand,H. S. (1991) Models of S-phase determination in lymphomas from flow cytometric DNA content histograms: comparison with the bromodeoxyuridine labeling index.Hematol. Pathol. 5, 177–83.

    CAS  PubMed  Google Scholar 

  • Beck,H. P. (1981) Proliferation kinetics of perturbed cell populations determined by the bromodeoxyuridine-33258 technique: radiotoxic effects of incorporated [3H]thymidine.Cytometry 2, 170–4.

    CAS  PubMed  Google Scholar 

  • Begg,A. C. &Hofland,I. (1991) Cell kinetic analysis of mixed populations using three-colored fluorescence flow cytometry.Cytometry 12, 445–54.

    Article  CAS  PubMed  Google Scholar 

  • Begg,A. C.,Mcnally,N. J.,Shrieve,D. C. &Karcher,H. (1985) A method to measure the duration of DNA synthesis and the potential doubling time from a single sample.Cytometry 6, 620–6.

    Article  CAS  PubMed  Google Scholar 

  • Begg,A. C.,Hofland,L.,Moonen,L.,Bartelink,H.,Schraub,S.,Bontemps,P.,LeFur,R.,van denBogaert,W.,Caspers,R.,VanGlabekke,M. &Horiot,J. C. (1990) The predictive value of cell kinetic measurements in a European trial of accelerated fractionation in advanced head and neck tumours.Int. J. Rad. Oncol. Biol. Phys. 19, 1449–53.

    CAS  Google Scholar 

  • Begg,A. C.,Horland,I.,VanGlabeke,H. &Horiot,J. C. (1992) Predictive value of potential doubling time for radiotherapy of head and neck tumour patients: results from the EORTC Cooperative Trial 22851.Sem. Radiat. Oncol. 2, 22–5.

    Google Scholar 

  • Bennett,M. H.,Wilson,G. D.,Dische,S.,Saunders,M. I.,Martindale,C. A.,Robinson,B. M.,O'Haloran,A. E.,Leslie,M. D. &Laing,J. H. (1992) Tumour proliferation assessed by combined histological and flow cytometric analysis: implications for therapy in squamous cell carcinoma in the head and neck.Br. J. Cancer 65, 870–8.

    CAS  PubMed  Google Scholar 

  • Beisker,W.,Dolbeare,F. &Gray,J. W. (1987) An improved immunocytochemical procedure for high-sensitivity detection of incorporated bromodeoxyuridine.Cytometry 8, 235–9.

    Article  CAS  PubMed  Google Scholar 

  • Boehme,S. A. &Lenardo,M. J. (1993) Propriocidal apoptosis of mature T lymphocytes occurs at S-phase of the cell cycle.Eur. J. Immunol. 23, 1552–60.

    CAS  PubMed  Google Scholar 

  • Böhmer,R. M. (1979) Flow cytometric cell cycle analysis using the quenching of 33258 Hoechst fluorescence by bromodeoxyuridine incorporation.Cell Tissue Kinet. 12, 101–10.

    PubMed  Google Scholar 

  • Böhmer,R. M. &Ellwart,J. (1981a) Cell cycle analysis by combining the 5-bromodeoxyuridine/33258 Hoechst technique with DNA-specific ethidium bromide staining.Cytometry 2, 31–4.

    Article  PubMed  Google Scholar 

  • Böhmer,R. M. &Ellwart,J. (1981b) Combination of BUdR-quenched Hoechst fluorescence with DNA-specific ethidium bromide fluorescence for cell cycle analysis with a two-parameter flow cytometer.Cell Tissue Kinet. 14, 653–8.

    PubMed  Google Scholar 

  • Boon,M. (1991) BrdUrd labelling of S-phase cells in testes and small intestine of mice, using microwave irradiation for immunogold-silver staining [letter; comment] CM - Comment on:J. Histochem. Cytochem. Feb. 1990,38(2): 267–73.J. Histochem. Cytochem. 39, 380–1.

    CAS  PubMed  Google Scholar 

  • Boon,M. E. &Kok,L. P. (1988)Microwave Cookbook of Pathology: the Art of Microscopic Visualization. Leyden: Coloumb Press.

    Google Scholar 

  • Böswald,M.,Harasim,S. &Maurer-Schultze,B. (1990) Tracer dose and availability time of thymidine and bromodeoxyuridine: application of bromode-oxyuridine in cell kinetic studies.Cell Tissue Kinet. 23, 169–81.

    PubMed  Google Scholar 

  • Botto,Micca F.,Fasano,M. E.,Ardito,G. &Lamberti,L. (1980) Analysis of human lymphocyte cell cycle kinetics in vitro by incorporation into DNA of bromode-oxyuridine.Boil. Soc. Ital. Biol. Sper. 56, 725–31.

    Google Scholar 

  • Bourhis,J.,Wilson,G.,Wibault,P.,Bosq,J.,Chavaudra,N.,Janot,F.,Luboinski,B.,Eschwege,F. &Malaise,E. (1993)In vivo measurement of the potential doubling time by flow cytometry in oropharyngeal cancer treated by conventional radiotherapy.Int. J. Radiat. Oncol. Biol. Phys. 26, 793–9.

    CAS  PubMed  Google Scholar 

  • Brott,D. A.,Alvey,J. D.,Bleavins,M. R.,De LaIglesia,F. A. &Lalwani,N. D. (1993) Cell cycle dependent distribution of proliferating cell nuclear antigen/cyclin and cdc2-kinase in mouse T-lymphoma cells.J. Cell. Biochem.52, 362–72.

    Article  CAS  PubMed  Google Scholar 

  • Buley,I. D.,Morrison,E. H.,Kaklamanis,L.,Horak,E. &Gatter,K. C. (1992) Measuring proliferation in routine fine needle aspirates. Immunocytochemical detection of bromode-oxyuridine incorporation and Ki67 expression in breast aspirates.Cytopathology 3, 149–54.

    CAS  PubMed  Google Scholar 

  • Burgess,R.,Hyde,K.,Maguire,P. J.,Kelsey,P. R.,Yin,J. A. &Geary,C. G. (1992) Two-colour immunoenzymatic technique using sequential staining by APAAP to evaluate two cell antigens.J. Clin. Pathol. 45, 206–9.

    CAS  PubMed  Google Scholar 

  • Butti,G.,Gaetani,P.,Danova,M.,Assietti,R.,Girino,M. &Riccardi,A. (1989) Cell kinetic studies of human intracranial rumors.J. Neurosurg. Sci 33, 47–53.

    CAS  PubMed  Google Scholar 

  • Campana,D.,Coustan-Smith,E. &Janossy,G. (1988) Double and triple staining methods for studying the proliferative activity of human B and T lymphoid cells.J. Immunol. Meth. 107, 79–88.

    Article  CAS  Google Scholar 

  • Carayon,P. &Bord,A. (1992) Identification of DNA- replicating lymphocyte subsets using a new method to label the bromo-deoxyuridine incorporated into the DNA.J. Immunol. Meth. 147, 225–30.

    CAS  Google Scholar 

  • Carbajo,S.,Orfao,A.,Vicente-Villardon,J. L. &Carbajo-Perez,E. (1993) Expression of silver-stained nucleolar organizer regions is coupled to cell cycle in rat thymic cells.Cytometry 14, 46–52.

    Article  CAS  PubMed  Google Scholar 

  • Carbajo-Perez,E.,Alberca,V.,Vicente-Villardon,V.,Flores,T. &Carbajo,S. (1993) Expression of argyrophilic nucleolar organizer regions (AgNORs) can be used to assess cellular proliferation as shown in rat thymic sections.Histochem. J. 25, 548–53.

    Article  CAS  PubMed  Google Scholar 

  • Carlton,J. C.,Terry,N. H. &White,R. A. (1991) Measuring potential doubling times of murine tumours using flow cytometry.Cytometry 12, 645–50.

    Article  CAS  PubMed  Google Scholar 

  • Carroll,P. R.,Waldman,F. M.,Rosenau,W.,Cohen,M. B.,Vapnek,J. M.,FongP.,Narayan,P. &Mayall,B. H. (1993) Cell proliferation in prostatic adenocarcinoma: in vitro measurement by 5-bromodeoxyuridine incorporation and proliferating cell nuclear antigen expression.J. Urol. 149, 403–7.

    CAS  PubMed  Google Scholar 

  • Casas,F. C. &Jefferies,A. R. (1992) Comparison of intradermal injections of bromode-oxyuridine and tritiated thymidine in the in vivo measurement of epidermal cell turnover time in goats.Res. Vet. Sci. 52, 10–14.

    CAS  PubMed  Google Scholar 

  • Casasco,A.,Giordano,M.,Danova,M.,Casasco,M.,Icaro,Cornaglia, A. &Calligaro,A. (1993) PC10 monoclonal antibody to proliferating cell nuclear antigen as probe for cycling cell detection in developing tissues. A combined immunocytochemical and flow cytometric study.Histochemistry.99, 191–9.

    Article  CAS  PubMed  Google Scholar 

  • Cassanelli,S.,Guillaud,P.,Louis,J. &Seigneurin,D. (1991) Image cytometry of progesterone receptor expression during the cell cycle in the MCF-7 cell line.J. Histochem. Cytochem. 39, 1713–18.

    CAS  PubMed  Google Scholar 

  • Cawood,A. H. &Savage,J. R. (1983) A comparison of the use of bromode-oxyuridine and [3H]thymidine in studies of the cell cycle.Cell Tissue Kinet. 16, 51–7.

    CAS  PubMed  Google Scholar 

  • Chebotarev,A. N. &Selezneva,T. G. (1979) [Use of 5-bromodeoxyuridine for determining the duration of cell cycle phases] TT - [Ispol'zovanie 5-bromdezoksiuridina dlia opredeleniia prodolzhitel'nosti faz kletochnogo tsikla.]Tsitol Genet. 13, 163–7.

    CAS  PubMed  Google Scholar 

  • Chen,U. (1992) Application of BrdU/Hoechst-ethidium bromide two parameter flow cytometry in studying synchronous and non-synchronous mouse cells.Immunobiology 185, 366–79.

    CAS  PubMed  Google Scholar 

  • Chwalinski,S.,Potten,C. S. &Evans,G. (1988) Double labelling with bromodeoxyuridine and [3H]-thymidine of proliferative cells in small intestinal epithelium in steady state and after irradiation.Cell Tissue Kinet. 21, 317–29.

    CAS  PubMed  Google Scholar 

  • Clausen,O. P.,Berg,K. A.,Kirkhus,B.,De,AngelisP. &Huitfeldt,H. (1992) BrdUrd incorporation studies for evaluation of spermatogenesis in the blue fox.Cytometry 13, 374–80.

    Article  CAS  PubMed  Google Scholar 

  • Cohen,M. B.,Waldman,F. M.,Carroll,P. R.,Kerschmann,R.,Chew,K. &Mayall,B. (1993) Comparison of five histopathologic methods to assess cellular proliferation in transitional cell carcinoma of the urinary bladder.Hum. Pathol. 24, 772–8.

    CAS  PubMed  Google Scholar 

  • Coltrera,M. D. &Gown,A. M. (1990) PCNA/cyclin expression and BrdU uptake define different subpopulations in different cell lines.J. Histochem. Cytochem. 39, 23–30.

    Google Scholar 

  • Connolly,K. M. &Bogdanffy,M. S. (1993) Evaluation of proliferating cell nuclear antigen (PCNA) as an endogenous marker of cell proliferation in rat liver: a dual-stain comparison with 5-bromo-2′-deoxyuridine.J. Histochem. Cytochem. 41, 1–6.

    CAS  PubMed  Google Scholar 

  • Cottell,D. C.,Gilmartin,L. &Bannigan,J. G. (1989) Immunohistochemical staining of bromodeoxyuridine-labelled cells in the mouse embryo.J. Microsc. 156, 363–9.

    CAS  PubMed  Google Scholar 

  • Crissman,H. A. &Steinkamp,J. A. (1987) A new method for rapid and sensitive detection of bromodeoxyuridine in DNA-replicating cells.Exp. Cell Res. 173, 256–61.

    Article  CAS  PubMed  Google Scholar 

  • Crissman,H. A. &Steinkamp,J. A. (1990) Detection of bromode-oxyuridine-labelled cells by differential fluorescence analysis of DNA fluorochromes.Meth. Cell Biol. 33, 199–206.

    CAS  Google Scholar 

  • Crocker,J.,Macartney,J. C. &Smith,P. J. (1988) Correlation between DNA flow cytometric and nucleolar organizer region data in non-Hodgkins's lymphomas.J. Pathol. 154, 151–6.

    Article  CAS  PubMed  Google Scholar 

  • Crossen,P. E. &Morgan,W. F. (1981) Proliferation of PPD-stimulated lymphocytes measured by sister chromatid differential staining.Clin. Exp. Immunol. 45, 642–5.

    CAS  PubMed  Google Scholar 

  • Crossen,P. E.,Gerner,E. W.,Bell,C. W. &Trent,J. M. (1986) Analysis of the length of S-phase required to show sister chromatid differential staining.Cell Tissue Kinet. 19, 527–32.

    CAS  PubMed  Google Scholar 

  • Czernielewski,J. M. &Demarchez,M. (1990) Further evidence for the self-reproducing capacity of Langerhans cells in human skin.J. Invest. Dematol. 88, 17–20.

    Google Scholar 

  • Danova,M.,Lucotti,C.,Rosti,V.,Bergamaschi,G.,Riccardi,A. &Cassola,M. (1993a) In vivo growth characteristics of human CD34+ bone marrow cells after chemotherapy plus GM- or G-CSF.Blood 82 (suppl.), 497.

    Google Scholar 

  • Danova,M.,Pellicciai,C.,Zibera,C.,Mangiarotti,R.,Gibelli,N.,Giordano,M.,Wang,E.,Mazzini,G. &Riccardi,A. (1993b) Cell cycle kinetic effects of tomaxifen on human breast cancer cells: Flow cytometric analyses of DNA content, BrdU labelling, Ki-67, PCNA, and statin expression.Ann. N.Y. Acad. Sci. 698, 174–82.

    CAS  PubMed  Google Scholar 

  • Darzynkiewicz,Z.,Andreeff,M.,Traganos,F. &Melamed,M. R. (1978) Discrimination of cycling and non-cycling lymphocytes by BUdR-suppressed acridine orange fluorescence in a flow cytometric system.Exp. Cell Res. 115, 31–5.

    CAS  PubMed  Google Scholar 

  • Darzynkiewicz,Z.,Traganos,F. &Melamed,M. R. (1983) Distinction between 5-bromodeoxyuridine labelled and unlabelled mitotic cells by flow cytometry.Cytometry 3, 345–8.

    Article  CAS  PubMed  Google Scholar 

  • Dean,P. &Jett,J. (1974) Mathematical analysis of DNA distributions derived from flow cytometry.J. Cell Biol. 60, 523–7.

    Article  CAS  PubMed  Google Scholar 

  • Dean,P. N.,Dolbeare,F.,Gratzner,H.,Rice,G. C. &Gray,J. W. (1984) Cell-cycle analysis using a monoclonal antibody to BrdUrd.Cell Tissue Kinet. 17, 427–36.

    CAS  PubMed  Google Scholar 

  • Derenzini,M.,Pession,A.,Farabegoli,F.,Trerè,D.,Badiali,M. &Dehan,P. (1989) Relationship between interphasic nucleolar organizer regions and growth rate in two neuroblastoma cell lines.Am. J. Pathol. 134, 925–32.

    CAS  PubMed  Google Scholar 

  • Dinjens,W. N.,Ten,KateJ.,Lenders,M. H.,Van DerLindenE. P. &Bosman,F. T. (1992) Bromodeoxyuridine (BrdU) immunocytochemistry by exonuclease III (Exo III) digestion.Histochemistry 98, 199–205.

    Article  CAS  PubMed  Google Scholar 

  • Dolbeare,F. &Gray,J. W. (1988) Use of restriction endonucleases and exonuclease III to expose halogenated pyrimidines for immunochemical staining.Cytometry 9, 631–5.

    Article  CAS  PubMed  Google Scholar 

  • Dolbeare,F.,Gratzner,H.,Pallavicini,M. G. &Gray,J. W. (1983) Flow cytometric measurement of total DNA content and incorporated bromodeoxyuridine.Proc. Natl Acad. Sci. USA 80, 5573–7.

    CAS  PubMed  Google Scholar 

  • Dolbeare,F.,Beisker,W.,Pallavicini,M. G.,Vanderlaan,M. &Gray,J. W. (1985) Cytochemistry for bromodeoxyuridine/DNA analysis: stoichiometry and sensitivity.Cytometry 6, 521–30.

    Article  CAS  PubMed  Google Scholar 

  • Dolbeare,F.,Kuo,W. L.,Vanderlaan,M. &Gray,J. (1988) Cell cycle analysis of the incorporation of iododeoxyuridine (IdUrd) and bromodeoxyuridine (BrdUrd).Proc. Am. Assoc. Cancer Res. 29, 1896.

    Google Scholar 

  • Drouin,R.,Messier,P. E. &Richer,C. L. (1989a) Dynamic G- and R-banding of human chromosomes for electron microscopy.Chromosoma 98, 40–8.

    CAS  PubMed  Google Scholar 

  • Drouin,R.,Messier,P. E. &Richer,C. L. (1989b) DNA denaturation for ultrastructural banding and the mechanism underlying the fluorochrome-photolysis-Giemsa technique studied with anti-5-bromodeoxyur-idine antibodies.Chromosoma 98, 174–80.

    CAS  PubMed  Google Scholar 

  • Drouin,R.,Lemieux,N. &Richer,C. L. (1990) Analysis of DNA replication during S-phase by means of dynamic chromosome banding at high resolution.Chromosoma 99, 273–80.

    Article  CAS  PubMed  Google Scholar 

  • Durand,R. E. (1993) Determining Tpot in heterogenous systems: a new approach illustrated with multicell spheroids.Cytometry 14, 527–34.

    Article  CAS  PubMed  Google Scholar 

  • Dutrillaux,B.,Laurent,C.,Couturier,J. &Lejeune,J. (1973) Coloration des chromosomes humains par l'acridine orange apres traitment par le 5-bromode-oxyuridine.CR Acad. Sci. (D) 276, 3175–82.

    Google Scholar 

  • Edstrom,S. S.,Gustafsson,B.,Stenman,G.,Lyden,E.,Stein,H. &Westin,T. (1991) Proliferative pattern of head and neck cancer.Am. J. Surg. 162, 412–16.

    Article  CAS  PubMed  Google Scholar 

  • Epner,E.,Rifkind,R. A. &Marks,P. A. (1981) Replication of α and globin DNA sequences occurs during early S-phase in murine erythroleukemia cells.Proc. Natl Acad. Sci. USA 78, 3058–63.

    CAS  PubMed  Google Scholar 

  • Erba,E.,Giordano,M.,Danova,M.,Mazzini,G.,Ubezio,P.,Torri,V.,Mangioni,C.,Landoni,F.,Bolis,P.,Tenti,P.,Franchi,M.,Babilonti,L.,Riccardi,A. &Dincalci,M. (1994) Cell kinetics of human ovarian cancer with in vivo administration of bromode-oxyuridine.Ann. Oncology 5, 365–72.

    Google Scholar 

  • Fabry,L.,Decat,G. &Leonard,A. (1979) [Kinetics of division of human and rabbit lymphocytes stimulated by phytohemagglutinin, studied by means of the bromodeoxyuridine (BUDR) technic] TT.C. R. Soc. Seances Soc. Biol. Fil 173, 650–3.

    CAS  Google Scholar 

  • Falini,B.,Canino,S.,Sacchi,S.,Ciani,C.,Martelli,M. F.,Gerdes,J.,Stein,H.,Pileri,S.,Gobbi,M.,Fagioli,M.,Minelli,O. &Flenghi,L. (1988) Immunocytochemical evaluation of the percentage of proliferating cells in pathological bone marrow and peripheral blood samples with the Ki67 and anti-bromo-deoxyuridine monoclonal antibodies.Br. J. Haematol. 69, 311–20.

    CAS  PubMed  Google Scholar 

  • Fogt,F.,Wan,J.,O'Hara,C.,Bistrian,B. R.,Black-Burn,G. L. &Istfan,N. w. (1991) Flow cytometric measurement of cell cycle kinetics in rat Walker-256 carcinoma following in vivo and in vitro pulse labelling with bromodeoxyuridine.Cytometry 12, 33–41.

    Article  CAS  PubMed  Google Scholar 

  • Franchini,G.,Tusei,A.,Babilonti,L.,Donadello,N.,Franchi,M.,Zanaboni,F.,Tateo,S.,Mazzini,G.,Riccardi,A. &DanovA. M. (1994) DNA ploidy and proliferative activity in uterine tumors: an in vivo study using bromodeoxyuridine and flow cytometry.Oncology Reports 1, 65–7.

    Google Scholar 

  • Fujikawa-Yamamoto,K.,Miyashita,N. &Odashima,S. (1986) Flow cytometric determination of cell cycle parameters of V79 cells by continuous labelling with bromodeoxyuridine.Cell Struct. Funct. 11, 115–24.

    CAS  PubMed  Google Scholar 

  • Gaglia,P.,Bernardi,A.,Venesio,T.,Caldarola,B.,Lauro,D.,Cappa,A. P.,Calderini,P. &Liscia,D. S. (1993) Cell proliferation of breast cancer evaluated by anti-BrdU and anti-Ki67 antibodies: its prognostic value on short-term recurrences [see comments] CM- Comment in:Eur. J. Cancer 1993,29A(11): 1501–2.Eur. J. Cancer 29A, 1509–13.

    CAS  PubMed  Google Scholar 

  • Geido,E.,Giaretti,W. &Nusse,M. (1990) Detection of M and early-G1 phase cells by scattering signals combined with identification of G1, S, and G2 phase cells.Meth. Cell Biol. 33, 149–56.

    CAS  Google Scholar 

  • Georgian,L.,Ghyka,G. &Savi,I. (1990) S-phase detailed analysis in KB cells by bromdeoxyuridine labelling.Morphol. Embryol. (Bucur) 36, 163–5.

    CAS  Google Scholar 

  • Giaretti,W.,Nüsse,M.,Bruno,S.,DiVinciA. &Geido,E. (1989) A new method to discriminate G1, S, G2, M, and G1 postmitotic cells.Exp. Cell Res. 182, 290–5.

    Article  CAS  PubMed  Google Scholar 

  • Giordano,M.,Danova,M.,Mazzini,G.,Gobbi,P. &Riccardi,A. (1993) Cell kinetics with in vivo bromodeoxyuridine assay, proliferating cell nuclear antigen expression, and flow cytometric analysis. Prognostic significance in acute nonlymphoblastic leukemia.Cancer 71, 2739–45.

    CAS  PubMed  Google Scholar 

  • Girino,M.,Riccardi,A.,Luoni,R.,Ucci,G. &Cuomo,A. (1991) Monoclonal antibody Ki67 as a marker of proliferative activity in monoclonal gammopathies.Acta Haematol. 85, 26–30.

    CAS  PubMed  Google Scholar 

  • Gold,R.,Schmied,M.,Rothe,G.,Zischler,H.,Breitschopf,H.,Wekerle,H. &Lassmann,H. (1993) Detection of fragmentation in apoptosis: Application ofin situ nick translation to cell culture systems and tissue sections.J. Histochem. Cytochem. 41, 1023–30.

    CAS  PubMed  Google Scholar 

  • Goller,B. &Kubbies,M. (1992) UV lasers for flow cytometric analysis: HeCd versus argon laser excitation.J. Histochem. Cytochem. 40, 451–6.

    CAS  PubMed  Google Scholar 

  • Gonchoroff,N. J.,Katzmann,J. A.,Currie,R. M.,Evans,E. L.,Houck,D. W.,Kline,B. C.,Greipp,P. R. &Loken,M. R. (1986) S-phase detection with an antibody to bromodeoxyuridine. Role of DNase pretreatment.J. Immunol. Meth. 93, 97–101.

    Article  CAS  Google Scholar 

  • Gratzner,H. G. (1982) Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: A new reagent for detection of DNA replication.Science 218, 474–5.

    CAS  PubMed  Google Scholar 

  • Gratzner,H. G. &Leif,R. C. (1981) An immunofluorescence method for monitoring DNA synthesis by flow cytometry.Cytometry 1, 385–93.

    Article  CAS  PubMed  Google Scholar 

  • Gratzner,H. G.,Leif,R. C.,Ingram,D. J. &Castro,O. (1975) The use of antibody specific for bromodeoxyuridine for the immunofluorescent determination of DNA synthesis in single cells and chromosomes.Exp. Cell Res. 95, 88–94.

    Article  CAS  PubMed  Google Scholar 

  • Gratzner,H. G.,Pollack,A.,Ingram,D. J. &Leif,R. C., (1976) Deoxyribonucleic acid replication in single cells and chromosomes by immunologic techniques.J. Histochem. Cytochem. 24, 34–9.

    CAS  PubMed  Google Scholar 

  • Gratzner,H. G.,Ettinger,N.,Ingram,D. &Castro,A. (1978) Immunochemical studies of 5-bromodeoxyuridine.Res. Commun. Chem. Pathol. Pharmacol. 20, 539–48.

    CAS  PubMed  Google Scholar 

  • Gratzner,H. G.,Young,I. T. &Sher,S. E. (1979) An immunocytochemical approach to cell kinetics automation.J. Histochem. Cytochem. 27, 496–9.

    CAS  PubMed  Google Scholar 

  • Gray,J.,Carver,J.,George,Y. &Mendelsohn,M. (1977) Rapid cell cycle analysis by measurement of the radioactivity per cell in a narrow window in S-phase (RCSi).Cell Tissue Kinet. 10, 97–107.

    PubMed  Google Scholar 

  • Guillaud,P.,Vermont,J. &Seigneurin,D. (1991) Automatic classification of cells in cell cycle phases based on Ki67 antigen quantification by fluorescence microscopy.Cell Prolif. 24, 481–91.

    CAS  PubMed  Google Scholar 

  • Gutierrez-Gonzalez,M. G.,Hazen,M. J. &Espelosin,R. H. (1988) Harmine as a substitute for 33258 Hoechst in the FPG technique.Histochemistry 89, 199–200.

    Google Scholar 

  • Hamada,S. (1985) A double labeling technique combining [3H]-thymidine autoradiography with BrdUrd itnmunocytochemistry.Acta Histochem. Cytochem. 18, 267–73.

    CAS  Google Scholar 

  • Hanazono,M.,Yoshiki,A.,Ota,K.,Kitoh,J. &Kusakabe,M. (1990) DNA replication in uterine cells of adult and prepubertal mice under normal and hormonally stimulated conditions detected by bromodeoxyuridine labelling method.Endocrinol. Jpn. 37, 183–91.

    CAS  PubMed  Google Scholar 

  • Hara,A.,Niikawa,S.,Hirayama,H.,Sakai,N.,Yamada,H.,Ohno,T.,Tanaka,T. &Mori,H. (1991) Correlation between nucleolar organizer region score and bromodeoxyuridine labelling index in C6 glioma cell line.J. Neurooncol. 11, 149–55.

    CAS  PubMed  Google Scholar 

  • Hardonk,M. J. &Harms,G. (1990) The use of 5′-bromodeoxyuridine in the study of cell proliferation.Acta Histochem. (suppl.)39, 99–108.

    CAS  Google Scholar 

  • Harms,G.,Van,GoorH.,Koudstaal,J.,De,LeyL. &Hardonk,M. J. (1986) Immunohistochemical demonstration of DNA-incorporated 5-bromodeoxyuridine in frozen and plastic embedded sections.Histochemistry 85, 139–43.

    Article  CAS  PubMed  Google Scholar 

  • Harms,G.,VanGoorH.,Koudstaal,J.,DeLeyL. &Hardonk,M. J. (1987) Simultaneous immunohistochemical demonstration of antigen expression and 5-bromodeoxyuridine incorporation in plastic embedded sections.Histochemistry 86, 393–5.

    Article  CAS  PubMed  Google Scholar 

  • Harms,G.,VanGoorH.,Koudstaal,J.,DeLeyL. &Hardonk,M. J. (1988) Double immunohistochemical demonstration of antigen expression and DNA-incorporated 5-bromodeoxyuridine in frozen and plastic embedded sections.Acta Histochem (suppl.)36, 353–9.

    CAS  Google Scholar 

  • Hayashi,Y.,Koike,M.,Matsutani,M. &Hoshino,T. (1988) Effects of fixation time and enzymatic digestion on immunohistochemical demonstration of bromode-oxyuridine in formalin-fixed, paraffin-embedded tissue.J. Histochem. Cytochem. 36, 511–14.

    CAS  PubMed  Google Scholar 

  • Hayashi,Y.,Fukayama,M.,Koike,M.,Kaseda,S.,Ikeda,T. &Yokoyama,T. (1993) Cell-cycle analysis detecting endogenous nuclear antigens: comparison with BrdU-in vivo labelling and an application to lung tumours.Acta Pathol. Jpn. 43, 313–19.

    CAS  PubMed  Google Scholar 

  • Hilscher,W. &Maurer,W. (1962) Autoradiographische Bestimmung der DNA-Verdopplung und ihres zeitlichen Verlaufs bei Spermatogonien der Ratte durch Doppelmarkierung mit 14C-and 3H-Thymidin.Naturwissenschaften 49, 352–7.

    Article  CAS  Google Scholar 

  • Hoshino,T.,Nagashima,T.,Murovic,J.,Levin,E. M.,Levin,V. A. &Rupp,S.M. (1985) Cell kinetic studies of in situ human brain tumors with bromodeoxyuridine.Cytometry 6, 627–32.

    Article  CAS  PubMed  Google Scholar 

  • Hoshino,T.,Nagashima,T.,Murovic,J. A.,Wilson,C. B. &Davis,R. L. (1986) Proliferative potential of human meningiomas of the brain. A cell kinetics study with bromodeoxyuridine.Cancer 58, 1466–72.

    CAS  PubMed  Google Scholar 

  • Houck,D. W. &Loken,M. R. (1985) Simultaneous analysis of cell surface antigens, bromodeoxyuridine incorporation and DNA content.Cytometry 6, 531–8.

    Article  CAS  PubMed  Google Scholar 

  • Howell,W. M. &Black,D. A. (1980) Controlled silver staining of the nucleolus with protective colloidal developer. A one step method.Experentia 36, 1014–15.

    Article  CAS  Google Scholar 

  • Hoy,C. A.,Seamer,L. c. &Schimke,R. T. (1989) Thermal denaturation of DNA for immunochemical staining of incorporated bromodeoxyuridine (BrdUrd): critical factors that affect the amount of fluorescence and the shape of the BrdUrd/DNA histogram.Cytometry 10, 718–25.

    Article  CAS  PubMed  Google Scholar 

  • HØyer,M.,Bentzen,S. M.,Salling,L. N. &Overgaard,J. (1994) Influence of sampling time on assessment of potential doubling time.Cytometry 16, 144–51.

    Article  PubMed  Google Scholar 

  • Huang,H. X. (1992) [Agyrophilic nucleolar organizer region counts as related to bromodeoxyuridine incorporation scores in ovarian clear cell carcinoma cells].Chung Hua Chung Liu Tsa Chih 14, 87–90.

    CAS  PubMed  Google Scholar 

  • Humbert,C.,Giroud,F. &Brugal,G. (1990) Detection of S cells and evaluation of DNA denaturation protocols by image cytometry of fluorescent BrdUrd labelling.Cytometry 11, 481–9.

    Article  CAS  PubMed  Google Scholar 

  • Humbert,C.,Santisteban,M. S.,Usson,Y. &Robertnicoud,M. (1992) Intranuclear co-location of newly replicated DNA and PCNA by simultaneous immunofluorescent labelling and confocal microscopy in MCF-7 cells.J. Cell Science 103, 97–103.

    CAS  PubMed  Google Scholar 

  • Hume,W. J. (1989) DNA-synthesizing cells in oral epithelium have a range of cell cycle durations: evidence from double-labelling studies using tritiated thymidine and bromodeoxyuridine.Cell Tissue Kinet. 22, 377–82.

    CAS  PubMed  Google Scholar 

  • Hume,W. J. (1990) A reproducible technique combining tritiated thymidine autoradiography with immuno-detection of bromodeoxyuridine for double labelling studies of cell proliferation in paraffin sections of tissues.Cell Tissue Kinet. 23, 161–8.

    CAS  PubMed  Google Scholar 

  • Hume,W. J. &Keat,S. (1990) Immunohistological optimization of detection of bromodeoxyuridine-labelled cells in decalcified tissue.J. Histochem. Cytochem. 38, 509–13.

    CAS  PubMed  Google Scholar 

  • Hume,W. J. &Thompson,J. (1989) Double labelling of tissue combining tritiated thymidine autoradiography with immunodetection of bromode-oxyuridine: the autoradiographic significance of inhibition of thymidine incorporation into DNA.Cell Tissue Kinet. 22, 393–9.

    CAS  PubMed  Google Scholar 

  • Hume,W. J. &Thompson,J. (1990) Double labelling of cells with tritiated thymidine and bromodeoxyuridine reveals a circadian rhythm-dependent variation in duration of DNA synthesis and S-phase flux rates in rodent oral epithelium.Cell Tissue Kinet. 23, 313–23.

    CAS  PubMed  Google Scholar 

  • Ibayashi,N.,Hirakawa,K.,Suzuki,K.,Nakamura,K. &Houri,T. (1988) [Immunohistochemical study of S-phase cells in human gliomas.]No To Shinkei 40, 763–9.

    CAS  PubMed  Google Scholar 

  • Ibayashi,N.,Herman,M. M.,Boyd,J. C.,Bigner,D. D.,Friedman,H. S.,Collins,V. P.,Donoso,L. A. &Rubinstein,L. J. (1989) Relationship of the demonstration of intermediate filament protein to kinetics of three human neuroepithelial tumour cell lines. Lack of neural-related proteins in most cells in S-phase: a double-label es.Lab. Invest. 61, 310–18.

    CAS  PubMed  Google Scholar 

  • Inoue,S. &Mizuno,S. (1992) [The theory of flow cytometric analysis of the cell cycle and their applications in biology and oncology.]Nippon Rinsho 50, 2324–32.

    CAS  PubMed  Google Scholar 

  • Isobe,H.,Shimizu,T.,Haneda,H.,Mizuno,S.,Ishiguro,A.,Araya,Y.,Harada,M.,Miyamoto,H. &Kawakami,Y. (1988) [Cell cycle analysis using the monoclonal antibody Ki67]Hum. Cell 1, 218–24.

    CAS  PubMed  Google Scholar 

  • Jensen,P. Ø.,Larsen,J.,Christiansen,J. &Larsen,J. K. (1993) Flow cytometric measurement of RNA synthesis using bromouridine labelling and bromodeoxyuridine antibodies.Cytometry 14, 455–8.

    Article  CAS  PubMed  Google Scholar 

  • Jensen,P. Ø.,LarsenK. J.,Christensen,I. J. &VanErp,P. E. J. (1994) Discrimination of bromode-oxyuridine labelled and unlabelled mitotic cells in flow cytometric bromode-oxyuridine/DNA analysis.Cytometry 15, 154–61.

    Article  CAS  PubMed  Google Scholar 

  • Kanno,M.,Takeda,Y. &Nakamura,S. (1992) [Application of bromode-oxyuridine (BrdU) and anti-BrdU monoclonal antibody for the analysis of tumor cell kinetics by flow cytometry.]Nippon Rinsho 50, 2333–7.

    CAS  PubMed  Google Scholar 

  • Kato,H. (1974) Spontaneous sister chromatid exchange detected by a BUdR labelling method.Nature 251, 70–2.

    Article  CAS  PubMed  Google Scholar 

  • Kaufman,S. J. &Robert-Nicoud,M. (1985) DNA replication and differentiation in rat myoblasts studied with monoclonal antibodies against 5-bromodeoxyuridine, actin, and alpha 2-macroglobulin.Cytometry 6, 570–7.

    Article  CAS  PubMed  Google Scholar 

  • Kawauchi,K.,Sato,Y.,Furuya,T. &Watanabe,S. (1989) Determination of proliferative fractions detected by immunohistochemistry with the monoclonal antibodies to bromodeoxyuridine and Ki67 in malignant lymphomas.Hematol. Oncol. 7, 257–65.

    CAS  PubMed  Google Scholar 

  • Kim,M. A. (1974) Chromatidaustausch und Heterochromatinveranderungen menschlicher Chromosomen nach BUdR-Markierung. Nachweis mit Bensimidazolfluorochrom und Giemsafarbstoff.Hum. Genet. 25, 179–85.

    Article  CAS  Google Scholar 

  • Kirkhus,B. &Clausen,O. p. (1990) Cell kinetics in mouse epidermis studied by bivariate DNA/bromodeoxyuridine and DNA/keratin flow cytometry.Cytometry 11, 253–60.

    Article  CAS  PubMed  Google Scholar 

  • Kitaiima,T.,Okuhira,M.,Tani,K.,Nakano,T.,Hiramatu,A.,Mizuno,T.,Inoue,K. &Yamada,H. (1992) [Cell proliferation kinetics in the rat gastric mucosa evaluated by immunohistochemical staining of PCNA-compared with immunohistochemical staining of BrdU.]Nippon Shokakibyo Gakkai Zasshi 89, 1471.

    Google Scholar 

  • Korenberg,J. &Freedlender,E. (1974) Giemsa technique for detection of sister chromatid exchanges.Chromosoma 48, 355–62.

    Article  CAS  PubMed  Google Scholar 

  • Kubbies,M. &Rabinovitch,P. S. (1983) Flow cytometric analysis of factors which influence the BrdUrd-Hoechst quenching effect in cultivated human fibroblasts and lymphocytes.Cytometry 3, 276–81.

    Article  CAS  PubMed  Google Scholar 

  • Kubbies,M.,Goller,B. &VanBockstaele,D. R. (1992) Improved BrdUrd-Hoechst bivariate cell kinetic analysis by helium-cadmium single laser excitation.Cytometry 13, 782–86.

    Article  CAS  PubMed  Google Scholar 

  • Kuo,W. L.,Dolbeare,F.,Vanderlaan,M. &Gray,J. W. (1988) Simultaneous flow cytometric analysis of bromo- and iodo-deoxyuridine labelled brown Norway myelocytic leukemia cells.Proc. Am. Assoc. Cancer Res. 29, 1903.

    Google Scholar 

  • Kuo,W.L.,Dolbeare,F.,Vanderlaan,M. &Gray,J. W. (1993) Simultaneous flow cytometric analysis of bromo- and iodo-deoxyuridine labelled BN myelocytic leukemia cells inDNA Cytometric Analysis (edited bySampedro,A. &Orfao,A.), pp. 219–38. Oviedo, Spain: Oviedo University.

    Google Scholar 

  • Kurki,P.,Laasonen,A.,Tan,E. M. &Lehtonen,E. (1989) Cell proliferation and expression of cytokeratin filaments in F9 embryonal carcinoma cells.Development 106, 635–40.

    CAS  PubMed  Google Scholar 

  • Lacombe,F.,Belloc,F.,Bernard,P. &Boisseau,M. R. (1988) Evaluation of four methods of DNA distribution data analysis based on bromodeoxyuridine/DNA bivariate data.Cytometry 9, 245–53.

    Article  CAS  PubMed  Google Scholar 

  • Landberg,G. &Roos,G. (1992) Flow cytometric analysis of proliferation associated antigens using washless staining of unfixed cells.Cytometry 13, 230–7.

    Article  CAS  PubMed  Google Scholar 

  • Larsen,J. K. (1990) Washless double staining of a nuclear antigen (Ki67 or bromodeoxyuridine) and DNA in unfixed nuclei.Meth. Cell Biol. 33, 227–34.

    CAS  Google Scholar 

  • Larsen,J. K.,Christensen,I. J.,Christiansen,J. &Mortensen,B. T. (1991) Washless double staining of unfixed nuclei for flow cytometric analysis of DNA and a nuclear antigen (Ki67 or bromodeoxyuridine).Cytometry 12, 429–37.

    Article  CAS  PubMed  Google Scholar 

  • Latt,S. A. (1973) Microfluorimetric detection of deoxyribonucleic acid replication in human metaphase chromosomes.Proc. Natl Acad. Sci. USA 70, 3395–9.

    CAS  PubMed  Google Scholar 

  • Latt,S. A. (1978) Analysis of sister chromatid exchange and chromosome replication kinetics using BrdU-dye techniques.Virchows Arch. B. Cell Pathol 29, 19–27.

    CAS  PubMed  Google Scholar 

  • Lazarous,D. F.,Shou,M. &Unger,E. F. (1992) Combined bromodeoxyuridine immunohistochemistry and Masson trichrome staining: facilitated detection of cell proliferation in viable vs. infarcted myocardium.Biotech Histochem. 67, 253–5.

    CAS  PubMed  Google Scholar 

  • Lee,K. S. &Yang,W. I. (1992) Comparison of brain tumour growth kinetics by proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU) labelling.Yonsei Med. J. 33, 265–71.

    CAS  PubMed  Google Scholar 

  • Li,X.,Traganos,F.,Melamed,M. R. &Darzynkiewicz,Z. (1994a) Detection of 5-bromo-2-deoxyuridine incorporated into DNA by labelling strand breaks induced by photolysis (SBIP).Internat. J. Oncology 4, 1157–61.

    CAS  Google Scholar 

  • Li,X.,Traganos,F. &Darzynkiewicz,Z. (1994b) Simultaneous analysis of DNA replication and apoptosis during treatment of HL-60 cells with camptothecin and hyperthermia and mitogen stimulation of human lymphocytes.Cancer Res. 54, 4289–93.

    CAS  PubMed  Google Scholar 

  • Limas,C.,Bigler,A.,Bair,R.,Bernhart,P. &Reddy,P. (1993) Proliferative activity of urothelial neoplasms: comparison of BrdU incorporation, Ki67 expression, and nucleolar organiser regions.J. Clin. Pathol. 46, 159–65.

    CAS  PubMed  Google Scholar 

  • Lin,M. S. &Alfi,O. S. (1978) Detection of lateral asymmetry in the C band of human chromosomes by BrdU-DAPI fluorescence.Somatic Cell Genet. 4, 603–8.

    Article  CAS  PubMed  Google Scholar 

  • Lin,P. &Allison,D. C. (1993) Measurement of DNA content and of tritiated thymidine and bromodeoxyuridine incorporation by the same cells.J. Histochem. Cytochem. 41, 1435–39.

    CAS  PubMed  Google Scholar 

  • Lokhorst,H. M.,Boom,S. E.,Bast,B. J. &Ballieux,R. E. (1986) Determination of the plasma cell labelling index with bromodeoxyuridine in a double fluorescence technique.Br. J. Haematol. 64, 271–5.

    CAS  PubMed  Google Scholar 

  • Maddox,A. M.,Johnson,D. A. &Keating,M. J. (1989) 5-bromodeoxyuridine (BUdR) quenching of acridine orange fluorescence distinguishes cycling and non-cycling normal and malignant bone marrow cells in vitro.Leuk. Res. 13, 781–90.

    Article  CAS  PubMed  Google Scholar 

  • Maeda,T. &Hoshino,T. (1992) [Proliferation kinetics of human brain tumours by in situ double labelling with bromodeoxyuridine and iododeoxyuridine.]No To Shinkei 44, 821–5.

    CAS  PubMed  Google Scholar 

  • Magaud,J.P.,Sargent,I.,Clarke,P. J.,Ffrench,M.,Rimokh,R. &Mason,D. Y. (1989) Double immuno-cytochemical labelling of cell and tissue samples with monoclonal anti-bromodeoxyuridine.J. Histochem. Cytochem. 31, 1517–27.

    Google Scholar 

  • Manders,E. M. M.,Stap,J.,Brakenhoff,G. J.,VanDriel,R. &Aten,J. A. (1992) Dynamics of three-dimensional replication patterns during the S-phase, analysed by double labelling of DNA and confocal microscopy.J. Cell Sci. 103, 857–62.

    CAS  PubMed  Google Scholar 

  • Maraldi,N. M.,Santi,S.,Zini,N.,Ognibene,A.,Rizzoli,R.,Mazzotti,G.,Di,PrimioR.,Bareggi,R.,Bertagnolo,V.,Pagliarini,C. et al. (1993) Decrease in nuclear phospholipids associated with DNA replication.J. Cell Sci. 104, 853–9.

    CAS  PubMed  Google Scholar 

  • Mariya,Y.,Aoki,M.,Tarusawa,N.,Takekawa,S.,Kaimori,M. &Abe,Y. (1993) [Determination of potential doubling time usingin vitro continuous labelling method with bromodeoxyuridine: estimation in head and neck squamous cell carcinoma].Nippon Igaku Hoshasen Gakkai Zasshi 53, 976–8.

    CAS  PubMed  Google Scholar 

  • Mattern,M. R. (1980) Differences between diploid and transformed human cells in the incorporation of 5-bromodeoxyridine into DNA.Exp. Cell Res. 18, 181–90.

    Google Scholar 

  • Mazzotti,G.,Rizzoli,R.,Galanzi,A.,Papa,S.,Vitale,M.,Falconi,M.,Neri,L. M.,Zini,N. &Maraldi,N. M. (1990) High-resolution detection of newly synthesized DNA by anti-bromodeoxyuridine antibodies identifies specific chromatin domains.J. Histochem. Cytochem. 38, 13–22.

    CAS  PubMed  Google Scholar 

  • Mehdi,A.,Bokhari,S. A.,Yousuf,N.,Umerani,A.,Chughtai,S.,Hussain,F. &Raza,A. (1992) A novel triple label method validates the double label technique of defining cell cycle kinetics in HL-60 cells.Anticancer Res. 12, 1443–6.

    CAS  PubMed  Google Scholar 

  • Messier,P. E.,Drouin,R. &Richer,C. L. (1989) Electron microscopy of gold-labelled human and equine chromosomes.J. Histochem. Cytochem. 37, 1443–7.

    CAS  PubMed  Google Scholar 

  • Migheli,A.,Mocellini,C. &Giordana,M. T. (1991) Ultrastructural detection of DNA-incorporated bromodeoxyuridine in resin embedded brain tissue.Histochemistry 95, 491–4.

    Article  CAS  PubMed  Google Scholar 

  • Miller,M. R.,Heyneman,C.,Walker,S. &Ulrich,R. G. (1986) Interaction of monoclonal antibodies directed against bromodeoxyuridine with pyrimidine bases, nucleosides, and DNA.J. Immunol. 136, 1791–5.

    CAS  PubMed  Google Scholar 

  • Miller,M. A.,Mazewski,C. M.,Yousuf,N.,Sheikh,Y.,White,L. M.,Yanik,G. A.,Hyams,D. M.,Lampkin,B. C. &Raza,A. (1991) Simultaneous immunohistochemical detection of IUdR and BrdU infused intravenously to cancer patients.J. Histochem. Cytochem. 39, 407–12.

    CAS  PubMed  Google Scholar 

  • Miller,M. A.,Bokhari,S. A.,Qadir,K. &Raza,A. (1992) Simultaneous assessment of TGFB and cell cycle kinetics using IUdR/BrdU infusions in human neoplasms from plastic-embedded tissue.J. Histochem. Cytochem. 40, 427–30.

    CAS  PubMed  Google Scholar 

  • Miura,M.,Domon,M.,Sasaki,T. &Takasaki,Y. (1992) Induction of proliferating cell nuclear antigen (PCNA) complex formation in quiescent fibroblasts from a xeroderma pigmentosum patient.J. Cell. Physiol. 150, 370–6.

    Article  CAS  PubMed  Google Scholar 

  • Montecucco,C. M.,Riccardi,A.,Traversi,E.,Mazzini,G.,Giordano,P. &Ascari,E. (1983) Proliferating activity of bone marrow cells in dysmyelopoietic (preleukemic) syndromes.Cancer 56, 1982–7.

    Google Scholar 

  • Montuenga,L. M.,Springall,D. R.,Gaer,J.,Mcbride,J. T. &Polak,J. M. (1992) Simultaneous immunostaining method for localization of bromode-oxyuridine and calcitonin gene-related peptide.J. Histochem. Cytochem 40, 1121–8.

    CAS  PubMed  Google Scholar 

  • Moran,R.,Darzynkiewicz,Z.,Staiano-Coico,L. &Melamed,M. R. (1985) Detection of 5-bromodeoxyuridine (BrdUrd) incorporation by monoclonal antibodies: role of the DNA denaturation step.J. Histochem. Cytochem. 33, 821–7.

    CAS  PubMed  Google Scholar 

  • Morenkov,O. S. &Mantsygin,I. U. A. (1990) The demonstration of proliferating cells by using monoclonal antibodies to 5-bromo-2′-deoxyuridine in the peroxidase-antiperoxidase method] TT.Tsitologiia 32, 1225–30.

    CAS  PubMed  Google Scholar 

  • Morimura,T.,Kitz,K.,Stein,H. &Budka,H. (1991) Determination of proliferative activities in human brain tumor specimens: a comparison of three methods.J. Neurooncol. 10, 1–11.

    Article  CAS  PubMed  Google Scholar 

  • Morstyn,G.,Hsu,S. M.,Kinsella,T.,Gratzner,H.,Russo,A. &Mitchell,J. B. (1983) Bromodeoxyuridine in tumours and chromosomes detected with a monoclonal antibody.J. Clin. Invest. 72, 1844–50.

    CAS  PubMed  Google Scholar 

  • Mourad,W. A.,Connelly,J. H.,Sembera,D. L.,Atkinson,E. N. &Bruner,J. M. (1993) The correlation of two argyrophilic nucleolar organizer region counting methods with bromodeoxyuridinelabelling index: a study of metastatic tumours of the brain.Hum. Pathol. 24, 206–10.

    Article  CAS  PubMed  Google Scholar 

  • Muir,D.,Varon,S. &Manthorpe,M. (1990) An enzyme-linked immunosorbent assay for bromodeoxyuridine incorporation using fixed microcultures.Anal. Biochem. 185, 377–82.

    Article  CAS  PubMed  Google Scholar 

  • Nakano,H.,Namatame,K.,Nakayoshi,A. &Kumada,K. (1993) [The evaluation of cellular proliferating activity in gastric carcinoma with the proliferating cell nuclear antigen (PCNA) expressive rate: its fundamental examination of the immunohistochemical procedures and its clinical applications].Nippon Geka Gakkai Zasshi 94, 580–92.

    CAS  PubMed  Google Scholar 

  • Nishizaki,T.,Orita,T.,Furutani,Y.,Ikeyama,Y.,Aoki,H. &Sasaki,K. (1989) Flow-cytometric DNA analysis and immunohistochemical measurement of Ki67 and BUdR labelling indices in human brain tumours.J. Neurosurg. 70, 379–84.

    CAS  PubMed  Google Scholar 

  • Nishizaki,T.,Orita,T.,Kamiryo,T.,Akimura,T.,Kajiwara,K.,Ikeda,N.,Ohshita,N.,Ito,H. &Sasaki,K. (1993) Measurement of labelling index of DNA polymerase alpha in human brain tumours. Comparative study with labelling indices of BUdR in vitro and Ki67.Clin. Neuropathol. 12, 160–3.

    CAS  PubMed  Google Scholar 

  • Nüsse,M.,Julch,M.,Geido,E.,Bruno,S.,DiVinciA.,Giaretti,W. &Ruoss,K. (1989) Flow cytometric detection of mitotic cells using the bromodeoxyuridine/DNA technique in combination with 90 degrees and forward scatter measurements.Cytometry 10, 312–19.

    Article  PubMed  Google Scholar 

  • Nylander,K.,Anneroth,G.,Gustafsson,H.,Roos,G.,Stenling,R. &Zackrisson,B. (1994) Cell kinetics of head and neck squamous cell carcinomas.Acta Oncologica 33, 23–8.

    CAS  PubMed  Google Scholar 

  • Olive,P. L. &Banath,J. P. (1992) Growth fraction measured using the comet assay.Cell Prolif. 25, 447–57.

    CAS  PubMed  Google Scholar 

  • Orita,T.,Kajiwara,K.,Nishizaki,T.,Ikeda,N.,Kamiryo,T. &Aoki,H. (1990) Nucleolar organizer regions in meningioma.Neurosurgery 26, 43–6.

    CAS  PubMed  Google Scholar 

  • Ormerod,M. G. &Kubbies,M. (1992) Cell cycle analysis of asynchronous cell populations by flow cytometry using bromodeoxyuridine label and Hoechst-propidium iodide stain.Cytometry 13, 678–85.

    Article  CAS  PubMed  Google Scholar 

  • Ormerod,M. G.,Titley,J. C.,Smithe,T. A.,Tomps,A. L. &Eccles,S. (1993) Proliferative behaviour of an oestrogen sensitive rat mamamary rumour evidence for a paracrine interaction between tumour and strom.Br. J. Cancer,67, 107–11.

    CAS  PubMed  Google Scholar 

  • Pallavicini,M. G.,Summers,L. J.,Dolbeare,F. A. &Gray,J. W. (1985) Cytokinetic properties of asynchronous and cytosine arabinoside perturbed murine tumours measured by simultaneous bromodeoxyuridine/DNA analyses.Cytometry 6, 602–10.

    CAS  PubMed  Google Scholar 

  • Parkins,C. S.,Bush,C.,Price,P. &Steel,G. G. (1991) Cell proliferation in human rumour xenografts: measurement using antibody labelling against bromodeoxyuridine and Ki67.Cell Prolif. 24, 171–9.

    CAS  PubMed  Google Scholar 

  • Penit,C. (1986) In vivo thymocyte maturation. BUdR labelling of cycling thymocytes and phenorypic analysis of their progeny support the single lineage model.J. Immunol. 137, 2115–20.

    CAS  PubMed  Google Scholar 

  • Penit,C. &Vasseur,F. (1988) Sequential events in thymocyte differentiation and thymus regeneration revealed by a combination of bromode-oxyuridine DNA labeling and antimitotic drug treatment.J. Immunol. 140, 3315–23.

    CAS  PubMed  Google Scholar 

  • Pera,F.,Mattias,P. &Detzer,K. (1977) Methods for determining the proliferation kinetics of cells by means of 5-bromodeoxyuridine.Cell Tissue Kinet. 10, 255–64.

    CAS  PubMed  Google Scholar 

  • Perry,P. &Wolff,S. (1974) New Giemsa method for the differential staining of sister chromatids.Nature 251, 156–8.

    Article  CAS  PubMed  Google Scholar 

  • Peters,G. J.,Laurensse,E.,Steinbusch,H. W.,DeVente,J.,Smid,K.,Van DerWilt,C. L. &Pinedo,H. M. (1993) Development, characterization and application of an antibody against 5-fluoro-2′deoxyuridine-5′monophosphate, the active metabolite of 5-fluorouracil.Anticancer Res. 13, 835–9.

    CAS  PubMed  Google Scholar 

  • Pilgrim,C.,Erb,W. &Mauer,W. (1962) Diurnal fluctuations in the number of DNA synthesizing nuclei in various mouse tissues.Nature 199, 863–5.

    Google Scholar 

  • Pinkel,D.,Thompson,L. H.,Gray,J. W. &Vanderlaan,M. (1987) Measurement of sister chromatid exchanges at very low bromodeoxyuridine substitution levels using a monoclonal antibody in Chinese hamster ovary cells.Cancer Res. 45, 5795–8.

    Google Scholar 

  • Ploton,D.,Menager,M.,Ieannesson,P.,Homber,G.,Pigeon,F. &Adnet,J. (1986) Improvement in the staining and visualization of argyrophilic proteins of the nucleolar organizer region at the optical level.Histochem. J. 58, 5–14.

    Google Scholar 

  • Pollack,A.,White,R. A.,Cao,S.,Meistrich,M. L. &Terry,N. H. A. (1993) Calculating potential doubling time (Tpot) using monoclonal antibodies specific for halogenated thymidine analogs.Int. J. Rad. Oncol. Biol. Phys. 27, 1131–9.

    CAS  Google Scholar 

  • Poot,M.,Schmitt,H.,Seyschab,H.,Koehler,J.,Chen,U.,Kaempf,U.,Kubbies,M.,Schindler,D.,Rabinovitch,P. S. &Hoehn,H. (1989) Continuous bromodeoxyuridine labelling and bivariate ethidium bromide/Hoechst flow cytometry in cell kinetics [published erratum appears inCytometry Sept. (1989); 10(5):670].Cytometry 10, 222–6.

    Article  CAS  PubMed  Google Scholar 

  • Poot,M.,Hoehn,H.,Kubbies,M.,Grossmann,A.,Chen,Y. C. &Rabinovitch,P. S. (1990) Cell cycle analysis using continuous bromodeoxyuridine labelling and Hoechst 33258-ethidium bromide bivariate flow cytometry.Meth. Cell Biol. 33, 185–8.

    CAS  Google Scholar 

  • Quastler,H. &Sherman,F. G. (1959) Cell population kinetics in the intestinal epthelium of the mouse.Exp. Cell Res. 17, 420–38.

    Article  CAS  PubMed  Google Scholar 

  • Rabinovitch,P. S.,Kubbies,M.,Chen,Y. C.,Schindler,D. &Hoehn,H. (1988) BrdU-Hoechst flow cytometry: a unique tool for quantitative cell cycle analysis.Exp. Cell Res. 174, 309–18.

    Article  CAS  PubMed  Google Scholar 

  • Raska,I.,Michjel,L. S.,Jarnik,M.,Dundr,M.,Fakan,S.,Gasser,S.,Gassmann,M.,Hubscher,U.,Izaurralde,E.,Martinez,E.,Richter.,A. &Dubochet,J. (1991) Utrastructural cryoimmunocytochemistry is a convenient tool for the study of DNA replication in cultured cells.J. Electron Microsc. Tech. 18, 91–105.

    Article  CAS  PubMed  Google Scholar 

  • Raza,A.,Preisler,H. D.,Mayers,G. L. &Bankert,R. (1984) Rapid enumeration of S-phase cells by means of monoclonal antibodies [letter].N. Engl. J. Med 310, 991.

    CAS  PubMed  Google Scholar 

  • Raza,A.,Spiridonidis,C.,Ucar,K.,Mayers,G.,Bankert,R. &Preisler,H. D. (1985a) Double labelling of S-phase murine cells with bromodeoxyuridine and a second DNA-specific probe.Cancer Res. 45, 2283–7.

    CAS  PubMed  Google Scholar 

  • Raza,A.,Ucar,K.,Bhayana,R.,Kempski,M. &Preisler,H. D. (1985b) Utility and sensitivity of anti BrdU antibodies in assessing S-phase cells compared to autoradiography.Cell Biochem. Funct. 3, 149–53.

    Article  CAS  PubMed  Google Scholar 

  • Raza,A.,Miller,M. A.,Mazewski,C.,Sheikh,Y.,Lampkin,B.,Sawaya,R.,Crone,K.,Berger,T.,Reising,J.,Gray,J. et al. (1991) Observations regarding DNA replication sites in human cells in vivo following infusions of iododeoxyuridine and bromodeoxyuridine.Cell Prolif. 24, 113–26.

    CAS  PubMed  Google Scholar 

  • Raza,A.,Yousuf,N.,Bohkari,S. A.,Sheikh,Y.,Akhtar,S.,Chughtai,S.,Umerani,A.,Mehdi,S. A.,Miller,M. A.,Masterson,M. et al. (1992) In situ cell cycle kinetics in bone marrow biopsies following sequential infusions of IUdR/BrdU in patients with hematopoietic malignancies.Leuk. Res. 16, 299–306.

    Article  CAS  PubMed  Google Scholar 

  • Raza,A.,Preisler,H.,Lampkin,B.,Lykins,J.,Kukla,C.,Gartside,P.,Sheikh,Y.,Yousuf,N.,White,M.,Barcos,M.,et al. (1993) Clinical and prognostic significance of in vivo differentiation in acute myeloid leukemia.Am. J. Hermatol. 42, 147–57.

    CAS  Google Scholar 

  • Riccardi,A.,Montecucco,C. M.,Danova,M.,Ucci,G.,Mazzini,G.,Giordano,P. &Pasquali,F. (1986) Flow cytometric evaluation of proliferative activity and ploidy in myelodysplastic syndromes and acute leukemias.Basic Appl. Histochem. 30, 181–92.

    CAS  PubMed  Google Scholar 

  • Riccardi,A.,Danova,M.,Dionigi,P.,Gaetani,P.,Cebrelli,T.,Butti,G.,Mazzini,G. &Wilson,G. (1989) Cell kinetics in leukaemia and solid tumours studied with in vivo bromodeoxyuridine and flow cytometry.Br. J. Cancer 59, 898–903.

    CAS  PubMed  Google Scholar 

  • Richter,F.,Richter,A.,Yang,K. &Lipkin,M. (1992) Cell proliferation in rat colon measured with bromodeoxyuridine, proliferating cell nuclear antigen, and [3H]thymidine.Cancer Epidemiol. Biomarkers Prev. 1, 561–6.

    CAS  PubMed  Google Scholar 

  • Risio,M. (1992) Cell proliferation in colorectal tumor progression: an immunohistochemical approach to intermediate biomarkers.J. Cell. Biochem. Suppl. 16G, 79–87.

    CAS  PubMed  Google Scholar 

  • Risio,M.,Candelaresi,G. &Rossini,F. P. (1993) Bromodeoxyuridine uptake and proliferating cell nuclear antigen expression throughout the colorectal tumour sequence.Cancer Epidemiol. Biomarkers Prev. 2, 363–7.

    CAS  PubMed  Google Scholar 

  • Ritter,M. A.,Fowler,J. F.,KimY.,LindstromM. J. &Kinsella,T. J. (1992) Single biopsy, tumour kinetic analysis: a comparison of methods and an extension to shorter sampling intervals.Int. J. Radiat. Oncol. Biol. Phys. 23, 811–20.

    CAS  PubMed  Google Scholar 

  • Ritter,M. A.,Fowler,J. F.,Kim,Y. J.,Gilchrist,K. W.,Morrisey,L. W. &Kinsella,T. J. (1994a) Tumour cell kinetics using two labels and flow cytometry.Cytometry 16, 49–58.

    CAS  PubMed  Google Scholar 

  • Ritter,M. A.,Albrectson,J. L.,KimY. J. &Kinsella,T. J. (1994b) Tumour cell kinetics in mixed populations.Cytometry 16, 118–28.

    CAS  PubMed  Google Scholar 

  • Ross,D. A.,Huaman,J. A.,Barsky,S. H. (1992) A study of the heterogeneity of the mucoepidermoid tumor and the implication for future therapies.Arch. Otolaryngol. Head Neck Surg. 118, 1172–8.

    CAS  PubMed  Google Scholar 

  • Sanders,E. J.,Varedi,M. &French,A. S. (1993) Cell proliferation in the gastrulating chick embryo: a study using BrdU incorporation and PCNA localization.Development 118, 389–99.

    CAS  PubMed  Google Scholar 

  • Sarraf,C. E.,Ansari,T. W.,Conway,P.,Notay,M.,Hill,S. &Alison,M. R. (1993) Bromodeoxyuridine-labelled apoptosis after treatment with antimetabolites in two murine tumours and in small intestinal crypts.Br. J. Cancer 68, 678–80.

    CAS  PubMed  Google Scholar 

  • Sasaki,K.,Murakami,T.,Ogino,T.,Takahashi,M. &Kawasaki,S. (1986a) Flow cytometric estimation of cell cycle parameters using a monoclonal antibody to bromodeoxyuridine.Cytometry 7, 391–5.

    Article  CAS  PubMed  Google Scholar 

  • Sasaki,K.,Ogino,T. &Takahashi,M. (1986b) Irnmunological determination of labelling index on human tumour tissue sections using monoclonal anti-BrdUrd antibody.Stain Technol. 61, 155–61.

    CAS  PubMed  Google Scholar 

  • Sasaki,K.,Murakami,T. &Takahashi,M. (1987) A rapid and simple estimation of cell cycle parameters by continuous labelling with bromodeoxyuridine.Cytometry 8, 526–8.

    CAS  PubMed  Google Scholar 

  • Sasaki,K.,Adachi,S.,Yamamoto,T.,Murakami,T.,Tanaka,K. &Takahashi,M. (1988a) Effects of denaturation with HCl on the immunological staining of bromode-oxyuridine incorporated into DNA.Cytometry 9, 93–6.

    Article  CAS  PubMed  Google Scholar 

  • Sasaki,K.,Matsumura,K.,Tsuji,T.,Shinozaki,F. &Takahashi,M. (1988b) Relationship between labelling indices of Ki67 and BrdUrd in human malignant tumours.Cancer 62, 989–93.

    CAS  PubMed  Google Scholar 

  • Sasaki,A.,Naganuma,H.,Kimura,R.,Isoe,S.,Nakano,S.,Nukui,H.,Suzuki,K. &Kawaoi,A. (1992) Proliferating cell nuclear antigen (PCNA) immunostaining as an alternative to bromodeoxyuridine (BrdU) immunostaining for brain tumours in paraffin embedded sections.Acta Neurochir (Vienna)117, 178–81.

    CAS  Google Scholar 

  • Sasaki,K.,Kurose,A. &Ishida,Y. (1993) Flow cytometric analysis of the expression of PCNA during the cell cycle in HeLa cells and effects of the inhibition of DNA synthesis on it.Cytometry 14, 876–82.

    Article  CAS  PubMed  Google Scholar 

  • Savino,W. &Dardenne,M. (1985) Analysis of thymic epithelial cell proliferation in vitro by combining bromodeoxyuridine and keratin labeling in an immunofluorescence assay.J. Immunol. Meth. 85, 221–6.

    Article  CAS  Google Scholar 

  • Schutte,B.,Reynders,M. M.,Bosman,F. T. &Blijham,G. H. (1987a) Studies with anti-bromodeoxyuridine antibodies: II. Simultaneous immunocytochemical detection of antigen expression and DNA synthesis by in vivo labelling of mouse intestinal mucosa.J. Histochem. Cytochem. 35, 371–4.

    CAS  PubMed  Google Scholar 

  • Schutte,B.,Reynders,M. M.,Bosman,F. T. &Blijham,G. H. (1987b) Effect of tissue fixation on anti-bromodeoxyuridine immunohistochemistry.J. Histochem. Cytochem. 35, 1343–5.

    CAS  PubMed  Google Scholar 

  • Schutte,B.,Reynders,M. M.,VanAsscheC. L.,Hupperets,P. S.,Bosman,F. T. &Blijham,G. H. (1987c) An improved method for the immunocyto-chemical detection of bromodeoxyuridine labelled nuclei using flow cytometry.Cytometry 8, 372–6.

    Article  CAS  PubMed  Google Scholar 

  • Scucchi,L.,Silecchia,G.,Di,StefanoD.,Spaziani,E.,Polimeno,L.,Materia,A.,Mingazzini,P. L.,Basso,N. &Marinozzi,V. (1992) Interphasic nucleolar organizer regions expression and cell kinetics evaluation during gastric carcinogenesis induced by nitrosoguanidine in the rat.Virchows Arch. B. Cell Pathol. 62, 303–9.

    CAS  Google Scholar 

  • Sebo,T. J.,Roche,P. C.,Witzig,T. E. &Kurtin,P. J. (1993) Proliferative activity in non-Hodgkin's lymphomas. A comparison of the bromodeoxyuridine labelling index with PCNA immunostaining and quantitative image analysis.Am. J. Clin. Pathol. 99, 668–72.

    CAS  PubMed  Google Scholar 

  • Selden,J. R.,Dolbeare,F.,Clair,J. H.,Nichols,W. W.,Miller,J. E.,Kleemeyer,K. M.,Hyland,R. J. &DeLucaJ. G. (1993) Statistical confirmation that immunofluorescent detection of DNA repair in human fibroblasts by measurement of bromode-oxyuridine incorporation is stoichiometric and sensitive.Cytometry 14, 154–67.

    Article  CAS  PubMed  Google Scholar 

  • Shang,K.,Lou,Z. &Wu,H. (1992) [Preparation and utilization of BrdU antiserum. II. Detections of BrdU labelling chromosome and DNA using BrdU antibody technique.]Chuan Hsueh Pao 19, 385–9.

    CAS  Google Scholar 

  • Shibui,S.,Hoshino,T.,Iwasaki,K.,Nomura,K. &Jastreboff,M. M. (1989a) Cell cycle phase dependent emergence of thymidylate synthase studied by monoclonal antibody (M-TS-4).Cell Tissue Kinet. 22, 259–68.

    CAS  PubMed  Google Scholar 

  • Shibui,S.,Hoshino,T.,Vanderlaan,M. &Gray,J. W., (1989b) Double labelling with iodo- and bromodeoxyuridine for cell kinetics studiesJ. Histochem. Cytochem. 37, 1007–11.

    CAS  PubMed  Google Scholar 

  • Shibuya,M.,Saito,F.,Miwa,T.,Davis,R.L.,Wilson,C. B. &Hoshino,T. (1992) Histochemical study of pituitary adenomas with Ki67 and anti-DNA polymerase alpha monoclonal antibodies, bromodeoxyuridine labelling, and nucleolar organizer region counts.Acta Neuropathol. (Berlin) 84, 178–83.

    Article  CAS  Google Scholar 

  • Shibuya,M.,Ito,S.,Davis,R. L. &Hoshino,T. (1993a) Immunohistochemical double staining with immuno-gold-silver and alkaline phosphatase to identify nuclear markers of cellular proliferation.Biotech. Histochem. 68, 17–19.

    CAS  PubMed  Google Scholar 

  • Shibuya,M.,Ito,S.,Davis,R. L.,Wilson,C. B. &Hoshino,T. (1993b) A new method for analyzing the cell kinetics of human brain tumours by double labelling with bromodeoxyuridine in situ and with iododeoxyuridine in vitro.Cancer 71, 3109–13.

    CAS  PubMed  Google Scholar 

  • Shibuya,M.,Ito,S.,Miwa,T.,Davis,R. L.,Wilson,C. B. &Hoshino,T. (1993c) Proliferative potential of brain tumours. Analyses with Ki67 and anti-DNA polymerase alpha monoclonal antibodies, bromodeoxyuridine labelling, and nuclear organizer region counts.Cancer 71, 199–206.

    CAS  PubMed  Google Scholar 

  • Sigmund,J.,Schwarzacher,H. G. &Mikelsaar,A. V. (1979) Satellite association frequency and number of nucleoli depend on cell cycle duration and NOR-activity. Studies on first, second, and third mitoses of lymphocyte cultures.Hum. Genet. 50, 81–91.

    Article  CAS  PubMed  Google Scholar 

  • Silvestrini,R.,Piazza,R.,Riccardi,A. &Rilke,F. (1977) Correlation of cell kinetic findings with morphology of non-Hodgkin's lymphomas.J. Natl Cancer Inst. 58, 499–507.

    CAS  PubMed  Google Scholar 

  • Silvestrini,R.,Daidone,M. G. &Gasparini,G. (1985) Cell kinetics as a prognostic marker in node-negative breast cancer.Cancer 56, 1982–7.

    CAS  PubMed  Google Scholar 

  • Smedman,L.,Joki,A.,Perlmann,P. &Troyeblomberg,M. (1991) Whole-blood microassay for immunodetection of antigen specific cell mediated immunity using bromodeoxyuridine incorporation.J. Clin. Lab. Immunol. 34, 79–85.

    CAS  PubMed  Google Scholar 

  • Smith,P. J.,Howes,E. A. &Treherne,J. E. (1990) Cell proliferation in the repairing adult insect central nervous system: incorporation of the thymidine analogue 5-bromo-2-deoxyuridine in vivo.J. Cell Sci. 95, 599–604.

    CAS  PubMed  Google Scholar 

  • Srivastava,V.,Miller,S. &Busbee,D. (1993) Immunofluorescent evaluation of DNA repair synthesis using interactive laser cytometry.Cytometry 14, 144–53.

    Article  CAS  PubMed  Google Scholar 

  • Staquet,M. J.,De,FraissinetteA.,Dezutterdambuyant,C.,Schmitt,D. &Thivolet,J. (1989) A combined method for detection of cell surface marker expression and bromodeoxyuridine (BrdU) uptake by epidermal cells in suspension.J. Immunol. Meth. 116, 287–92.

    Article  CAS  Google Scholar 

  • Steel,G. G. (1977)Growth Kinetics of Tumours: Cell Populations Kinetics in Relation to the Growth and Treatment of Cancer. Oxford: Clarendon Press.

    Google Scholar 

  • Steinberg,J. J. (1993) A comparison of AgNOR staining and BUDR labelling of metastatic tumours of the brain [letter].Hum. Pathol. 24, 812–13.

    Article  CAS  PubMed  Google Scholar 

  • Stephenson,C. F.,Desai,Z. R. &Bridges,J. M. (1991) The proliferative activity of B-chronic lymphocytic leukaemia lymphocytes prior to and after stimulation with TPA and PHA.Leuk. Res. 15, 1005–12.

    Article  CAS  PubMed  Google Scholar 

  • Sugihara,H.,Hattori,T. &Fukuda,M. (1986) Immunohistochemical detection of bromodeoxyuridine in formalin-fixed tissues.Histochemistry 85, 193–5.

    Article  CAS  PubMed  Google Scholar 

  • Swartzendruber,D. E. (1977) A bromodeoxyuridine (BUdR)-mithramycin technique for detecting cycling and non-cycling cells by flow microfluorometry.Exp. Cell Res. 109, 439–43.

    Article  CAS  PubMed  Google Scholar 

  • Tabibzadeh,S. S.,Satyaswaroop,P. G. &Rao,P. N. (1988) Antiproliferative effect of interferon-gamma in human endometrial epithelial cells in vitro: potential local growth modulatory role in endometrium.J. Clin. Endocrinol. Metab. 67, 131–8.

    CAS  PubMed  Google Scholar 

  • Takagi,S.,Mcfadden,M. L.,Humphreys,R. E.,Woda,B. A. &Sairenji,T. (1993) Detection of 5-bromo-2-deoxyuridine (BrdUrd) incorporation with monoclonal anti-BrdUrd antibody after deoxyribonuclease treatment.Cytometry 14, 640–8.

    Article  CAS  PubMed  Google Scholar 

  • Takahashi,M. (1966) Theoretical basis for cell cycle analysis.J. Theoret. Biol. 13, 202–11.

    Google Scholar 

  • Takase,K.,Sawai,M.,Yamamoto,K.,Yata,J.,Takasaki,Y.,Teraoka,H. &Tsukada,K. (1992) Reversible G1 arrest induced by dimethyl sulfoxide in human lymphoid cell lines: kinetics of the arrest and expres-sion of the cell cycle marker proliferating cell nuclear antigen in Raji cells.Cell Growth Differ. 3, 515–21.

    CAS  PubMed  Google Scholar 

  • Takayama,S. &Hiramatsu,H. (1993) Scanning electron microscopy of the centromeric region of L-cell chromosomes after treatment with Hoechst 33258 combined with 5-bromodeoxyuridine.Chromosoma 102, 227–32.

    Article  CAS  PubMed  Google Scholar 

  • Takemoto,O.,Yoshimine,T.,Hayakawa,T.,Fujita,T.,Nakajima,S.,Taneda,M. &Mogami,H. (1989) [Astrocytic proliferation in the brain adjacent to infarcted lesion: immunohistochemical study of astroprotein (GFAP) and bromodeoxyuridine (BrdU).]No To Shinkei 41, 361–5.

    CAS  PubMed  Google Scholar 

  • Tanaka,T.,Takeuchi,T.,Nishikawa,A.,Takami,T. &Mori,H. (1989) Nucleolar organizer regions in hepatocarcinogenesis induced by N-2-fluorenylacetamide in rats: comparison with bromodeoxyuridine immunohistochemistry.Jpn. J. Cancer Res. 80, 1047–51.

    CAS  PubMed  Google Scholar 

  • Terry,N. H.,White,R. A.,Meistrich,M. L. &Calkins,D. P. (1991) Evaluation of flow cytometric methods for determining population potential doubling times using cultured cells.Cytometry 12, 234–41.

    Article  CAS  PubMed  Google Scholar 

  • Thiry,M. (1988) Immunoelectron microscope localization of bromode-oxyuridine incorporated into DNA of Ehrlich tumour cell nucleoli.Exp. Cell Res. 179, 204–13.

    Article  CAS  PubMed  Google Scholar 

  • Thiry,M. (1992a) Highly sensitive immunodetection of DNA on sections with exogenous terminal deoxynucleotidyl transferase and non-isotopic nucleotide analogues.J. Histochem. Cytochem. 40, 411–19.

    CAS  PubMed  Google Scholar 

  • Thiry,M. (1992b) Ultrastructural detection of DNA within the nucleolus by sensitive molecular immunocytochemistry.Exp. Cell Res. 200, 135–44.

    CAS  PubMed  Google Scholar 

  • Thiry,M. &Dombrowicz,D. (1988) Anti-bromodeoxyuridine monoclonal antibody: an alternative tool for the identification of replicated DNA at the electron microscope level.Biol. Cell 62, 99–102.

    Article  CAS  PubMed  Google Scholar 

  • Thiry,M.,Scheer,U. &Goessens,G. (1988) Immunoelectron microscopic study of nucleolar DNA during mitosis in Ehrlich tumour cells.Eur. J. Cell Biol. 47, 346–57.

    CAS  PubMed  Google Scholar 

  • Thoolen,B. (1990) BrdUrd labelling of S-phase cells in testes and small intestine of mice, using microwave irradiation for immunogold-silver staining: an immunocytochemical study [see comments] CM - Comment in:J. Histochem. Cytochem. March, 1991,39(3): 380–1.J. Histochem. Cytochem. 38, 267–73.

    Google Scholar 

  • Tinnemans,M. M.,Schutte,B.,Lenders,M. H.,Ten,Velde,G. P.,Ramaekers,F. C.,Blijham,G. H. (1993) Cytokinetic analysis of lung cancer by in vivo bromodeoxyuridine labelling.Br. J. Cancer 67, 1217–22.

    CAS  PubMed  Google Scholar 

  • Toba,K.,Winton,E. F. &Bray,R.A. (1992) Improved staining method for the simultaneous flow cytofluorometric analysis of DNA content, S-phase fraction, and surface phenotype using single laser instrumentation.Cytometry 13, 60–7.

    Article  CAS  PubMed  Google Scholar 

  • Tobey,R. A.,Valdez,J. G., &Crissman,H. A. (1988) Synchronization of human diploid fibroblasts at multiple stages in the cell cycle.Exp. Cell Res. 179, 400–16.

    Article  CAS  PubMed  Google Scholar 

  • Tobey,R. A.,Oishi,N. &Crissman,H. A. (1989) Synchronized human diploid fibroblasts: progression capabilities of a subpopulation that fails to keep pace with the predominant, rapidly dividing cohort of cells.J. Cell. Physiol. 139, 432–40.

    Article  CAS  PubMed  Google Scholar 

  • Traincard,F.,Ternynck,T.,Danchin,A. &Avrameas,S. (1983) Une technique immunoenzymatique pour la nise en evidence de l'hybridization moleculaire entre acides nucleiques.Ann. Immunol. (Paris)134D, 399–405.

    CAS  Google Scholar 

  • Trent,J. M.,Gerner,E.,Broderick,R. &Crossen,P. E. (1986) Cell cycle analysis using bromodeoxyuridine: comparison of methods for analysis of total cell transit time.Cancer Genet. Cytogenet. 19, 43–50.

    CAS  PubMed  Google Scholar 

  • Trere,D. (1993) Critical analysis of the methods commonly employed in the assessment of cell proliferation: advantages of the NOR silver-staining technique in routine cyto-histopathology [editorial].Anal. Cell Pathol. 5, 191–201.

    CAS  PubMed  Google Scholar 

  • Trere,D.,Farabegoli,F.,Cancellieri,A.,Ceccarelli,C.,Eusebi,V. &Derenzini,M. (1991) AgNOR area in interphase nuclei of human tumours correlates with the proliferative activity evaluated by bromode-oxyuridine labelling and Ki67 immunostaining.J. Pathol. 165, 53–9.

    CAS  PubMed  Google Scholar 

  • Tsujihashi,H.,Nakanishi,A.,Matsuda,H.,Uejima,S. &Kurita,T. (1991) Cell proliferation of human bladder tumours determined by BrdUrd and Ki67 immunostaining.J. Urol. 145, 846–9.

    CAS  PubMed  Google Scholar 

  • Ubezio,P. (1990) Cell cycle simulation for flow cytometry.Comput. Meth. Programs Biomed. 31, 255–66.

    Article  CAS  Google Scholar 

  • VanBockstaele,D. R.,Lardon,F.,Snoeck,H. W.,Peetermans,M. E. &Kubbies,M. (1992) BrdU-Hoechst-ethidium bromide (EB) quenching technique for studying kinetics of hematopoiesis [letter].Blood 80, 289–91.

    PubMed  Google Scholar 

  • van deKant,H. J. &DeRooij,D. G. (1992) Periodic acid incubation can replace hydrochloric acid hydrolysis and trypsin digestion in immunogold-silver staining of bromode-oxyuridine incorporation in plastic sections and allows the PAS reaction.Histochem. J. 24, 170–8.

    Article  PubMed  Google Scholar 

  • van deKant,H. J.,Boon,M. E. &DeRooij,D. G. (1988) Microwave-aided technique to detect bromodeoxyuridine in S-phase cells using immunogold-silver staining and plastic-embedded sections.Histochem. J. 20, 335–40.

    Article  PubMed  Google Scholar 

  • van deKant,H. J.,VanPeltA. M.,Vergouwen,R. P. &DeRooij,D. G. (1990) A rapid immunogold-silver staining for detection of bromode-oxyuridine in large numbers of plastic sections, using microwave irradiation.Histochem. J. 22, 321–6.

    PubMed  Google Scholar 

  • VanDierendonck,J. H.,Keijzer,R.,van deVelde,C. J. &Cornelisse,C. J. (1989a) Nuclear distribution of the RL67 antigen during the cell cycle: comparison with growth fraction in human breast cancer cells.Cancer Res. 49, 2999–3006.

    PubMed  Google Scholar 

  • VanErp,P. E.,Brons,P. P.,Boezeman,J. B.,DeJongh,G. J. &Bauer,F. W. (1988) A rapid flow cytometric method for bivariate bromodeoxyuridine/DNA analysis using simultaneous proteolytic enzyme digestion and acid denaturation.Cytometry 9, 627–30.

    PubMed  Google Scholar 

  • VanWeerden,W. M.,Moerings,E. P.,VanKreuningen,A.,DeJong,F. H.,VanSteenbrugge,G. J. &Schröder,F. H. (1993) Ki67 expression and BrdUrd incorporation as markers of proliferative activity in human prostate tumour models.Cell Prolif. 26, 67–75.

    PubMed  Google Scholar 

  • Vanderlaan,M. &Thomas,C. B. (1985) Characterization of monoclonal antibodies to bromodeoxyuridine.Cytometry 6, 501–5.

    Article  CAS  PubMed  Google Scholar 

  • Vanderlaan,M.,Watkins,B.,Thomas,C.,Dolbeare,F. &Stanker,L. (1986) Improved high-affinity monoclonal antibody to iododeoxyuridine.Cytometry 7, 499–507.

    Article  CAS  PubMed  Google Scholar 

  • Vitale,M.,Neri,L. M.,Manzoli,L.,Galanzi,A.,Rana,R.,Antonucci,A. &Papa,S. (1989) Improved bromodeoxyuridine/DNA analysis by anti-BudR monoclonal antibody versus right angle light scatter.Histochemistry 93, 9–11.

    Article  CAS  PubMed  Google Scholar 

  • Vitale,M.,Rizzoli,R.,Mazzotti,G.,Zamai,L.,Galanzi,A.,Rizzi,E.,Manzoli,L.,Matteucci,A. &Papa,S. (1991) Characterization and cell cycle kinetics of hepatocytes during rat liver regeneration: in vivo BrdUrd incorporation analysed by flow cytometry and electron microscopy.Cell Prolif. 24, 331–8.

    CAS  PubMed  Google Scholar 

  • Waldman,F. M.,Carroll,P. R.,Cohen,M. B.,Kerschmann,R.,Chew,K. &Mayall,B. H. (1993) 5-Bromodeoxyuridine incorporation and PCNA expression as measures of cell proliferation in transitional cell carcinoma of the urinary bladder.Mod. Pathol. 6, 20–4.

    CAS  PubMed  Google Scholar 

  • Walensky,L. D.,Coffey,D. S.,Chen,T. H.,Wu,T. C. &Pasternack,G. R. (1993) A novel M(r) 32,000 nuclear phosphoprotein is selectively expressed in cells competent for self-renewal.Cancer Res. 53, 4720–6.

    CAS  PubMed  Google Scholar 

  • Watanabe,T. &Raff,M. C. (1990) Rod photoreceptor development in vitro: intrinsic properties of proliferating neuroepithelial cells change as development proceeds in the rat retina.Neuron 4, 461–7.

    Article  CAS  PubMed  Google Scholar 

  • Wersto,R. P.,Herz,F.,Gallagher,R. E. &Koss,L. G. (1988) Cell cycle-dependent reactivity with the monoclonal antibody Ki67 during myeloid cell differentiation.Exp. Cell Res. 179, 79–88.

    Article  CAS  PubMed  Google Scholar 

  • White,R. A. &Meistrich,M. L. (1986) A comment on ‘A method to measure the duration of DNA synthesis and the potential doubling time from a single sample’.Cytometry 7, 486–90.

    CAS  PubMed  Google Scholar 

  • White,R. A. &Terry,N. H. (1992) A quantitative method for evaluating bivariate flow cytometric data obtained using monoclonal antibodies to bromodeoxyuridine.Cytometry 13, 490–5.

    CAS  PubMed  Google Scholar 

  • White,R. A.,Terry,N. H. &Meistrich,M. L. (1990) New methods for calculating kinetic properties of cells in vitro using pulse labelling with bromodeoxyuridine.Cell Tissue Kinet. 23, 561–73.

    CAS  PubMed  Google Scholar 

  • White,R. A.,Terry,N. H.,Baggerly,K. A. &Meistrich,M. L. (1991) Measuring cell proliferation by relative movement. I. Introduction and in vitro studies.Cell Prolif. 24, 257–70.

    CAS  PubMed  Google Scholar 

  • White,R. A.,Fallon,J. F. &Savage,M. P. (1992) On the measurement of cytokinetics by continuous labelling with bromodeoxyuridine with applications to chick wing buds.Cytometry 13, 553–6.

    CAS  PubMed  Google Scholar 

  • White,R. A.,Pollack,A. &Terry,H. A. (1994) Simultaneous cytokinetic measurement of aneuploid tumours and associated diploid cells following continuous labelling with chlorodeoxyuridine.Cytometry 15, 311–19.

    Article  CAS  PubMed  Google Scholar 

  • Wijsman,J. H.,VanDierendonckJ. H.,Keijzer,R.,van deVelde,C. J. &Cornelisse,C. J. (1992) Immunoreactivity of proliferating cell nuclear antigen compared with bromodeoxyuridine incorporation in normal and neoplastic rat tissue.J. Pathol. 168, 75–83.

    Article  CAS  PubMed  Google Scholar 

  • Williams,L. S.,Nordberg,J. A. &Chau,P. C. (1990) Evaluation of immunocytochemical detection methods of incorporated bromodeoxyuridine in hybridomas.Cytometry 11, 490–7.

    Article  CAS  PubMed  Google Scholar 

  • Williamson,K.,Gilliland,R.,Weir,H.,Grimes,J.,Hamilton,P.,Anderson,N.,Crockard,A. L. &Rowlands,B. (1994) Hydrochloric acid denaturation of colorectal tumour tissue infiltrated with bromodeoxyuridine.Cytometry 15, 162–8.

    Article  CAS  PubMed  Google Scholar 

  • Wilson,G. D. (1991) Assessment of human tumour proliferation using bromodeoxyuridine - current status.Acta Oncol. 30, 903–10.

    CAS  PubMed  Google Scholar 

  • Wilson,G. D. (1993) Limitations of the bromodeoxyuridine technique for measurement of rumour proliferation. InMedical Radiology, Current Topics in Clinical Radiobiology of Tumours (edited byBeck-Bomholdt,H. P.). Berlin: Springer-Verlag.

    Google Scholar 

  • Wilson,G. D. &Mcnally,N. J. (1991) Measurement of cell proliferation using bromodeoxyuridine. InCell Proliferation in Clinical Diagnosis, (edited byHall,P. A.,Levison,D. A. &Wright,N. A.), pp. 113–39. London: Springer-Verlag.

    Google Scholar 

  • Wilson,G. D.,Mcnally,N. J.,Dunphy,E.,Karcher,H. &Pfragner,R. (1985) The labelling index of human and mouse tumours assessed by bromodeoxyuridine staining in vitro and in vivo and flow cytometry.Cytometry 6, 641–7.

    Article  CAS  PubMed  Google Scholar 

  • Wilson,G. D.,Soranson,J. A. &Lewis,A. A. (1987) Cell kinetics of mouse kidney using bromodeoxyuridine incorporation and flow cytometry: preparation and staining.Cell Tissue Kinet. 20, 125–33.

    CAS  PubMed  Google Scholar 

  • Wilson,G. D.,Mcnally,N. J.,Dische,S. &Bennett,M. H. (1988a) Cell proliferation in human tumours measured by in-vivo labelling with bromode-oxyuridine.Br. J. Radiol. 61, 419–22.

    CAS  PubMed  Google Scholar 

  • Wilson,G. D.,Mcnally,N. J.,Dische,S.,Saunders,M. I.,Des,RochersC.,Lewis,A. A. &Bennett,M. H. (1988b) Measurement of cell kinetics in human tumours in vivo using bromodeoxyuridine incorporation and flow cytometry.Br. J. Cancer 58, 423–31.

    CAS  PubMed  Google Scholar 

  • Wilson,G. D.,Martindale,C. A.,Soranson,J. A.,Carl,U. M. &Mcnally,N. J. (1992) Proliferative changes in two murine tumours in response to single or fractionated doses of X-rays.Cell Prolif. 25, 415–30.

    CAS  PubMed  Google Scholar 

  • Wilson,M. S.,West,C. M. L.,Wilson,G. D.,Roberts,S. A.,James,R. D. &Schofield,P. F. (1993) An assessment of the reliability and reproducibility of measurement of potential doubling times (Tpot) in human colorectal tumours.Brit. J. Cancer. 67, 754–9.

    CAS  PubMed  Google Scholar 

  • Wimber,D. E. &Quastler,H. (1963) A 14C- and 3H-thymidine labelling technique in the study of cell proliferation inTradescantia root tips.Exp. Cell Res. 30, 8–17.

    Article  CAS  Google Scholar 

  • Yanagisawa,M.,Dolbeare,F.,Todoroki,T. &Gray,J. W. (1985) Cell cycle analysis using numerical simulation of bivariate DNA/bromodeoxyuridine distributions.Cytometry 6, 550–62.

    Article  CAS  PubMed  Google Scholar 

  • Yanik,G.,Yousuf,N.,Miller,M. A.,Swerdlow,S. H.,Lampkin,B. &Raza,A. (1992) In vivo determination of cell cycle kinetics of non-Hodgkin's lymphomas using iododeoxyuridine and bromodeoxyuridine.J. Histochem. Cytochem. 40, 723–8.

    CAS  PubMed  Google Scholar 

  • Yi,F. H.,Wang,B. M. &Liu,X. F. (1993) The significance of Ki67, BrdU and OKT9 expression in determination of myelodysplastic syndromes by use of APAAP technique.J. Tongji Med. Univ. 13, 30–3.

    CAS  PubMed  Google Scholar 

  • Yonemura,Y.,Kimura,H.,Fushida,S.,Tugawa,K.,Nakai,Y.,Kaji,M.,Fonseca,L.,Yamaguchi,A. &Miyazaki,I. (1993) Analysis of proliferative activity using anti-proliferating cell nuclear antigen antibody in gastric cancer tissue specimens obtained by endoscopic biopsy.Cancer 71, 2448–53.

    CAS  PubMed  Google Scholar 

  • Yoshinouchi,M. (1989) [Immunohistochemical approach to reveal the growth potential of uterine cancers using anti-BrdU antibody and Ki67].Nippon Gan Chiryo Gakkai Shi 24, 2513–21.

    CAS  PubMed  Google Scholar 

  • Yousuf,N.,Yanik,G. A.,George,B. A.,Masterson,M.,Mazewski,C. M.,White,L. M.,Miller,M. A.,Lampkin,B. C. &Raza,A. (1991) Comparison of two double labelling techniques to measure cell cycle kinetics in myeloid leukemias.Anticancer Res. 11, 1195–9.

    CAS  PubMed  Google Scholar 

  • Zätterström,U. K.,Johansson,M.,Kallen,A.,Baldetorp,B., Oredsson,S.,Wennerberg,J.,Killander,D. (1992) Comparison of BrdUrd and [3H]TdR incorporation to estimate cell proliferation, cell loss, and potential doubling time in tumor xenografts.Cytometry 13, 872–9.

    Article  PubMed  Google Scholar 

  • Zeymer,U.,Fishbein,M. C.,Forrester,J. S. &Cercek,B. (1992) Proliferating cell nuclear antigen immunohistochemistry in rat aorta after balloon denudation. Comparison with thymidine and bromodeoxyuridine labeling.Am. J. Pathol. 141, 685–90.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dolbeare, F. Bromodeoxyuridine: a diagnostic tool in biology and medicine, Part I: Historical perspectives, histochemical methods and cell kinetics. Histochem J 27, 339–369 (1995). https://doi.org/10.1007/BF02389022

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02389022

Keywords

Navigation