Abstract
Human KB cell lines resistant to high levels of colchicine were isolated by several successive single-step selections. Most of these selection steps resulted in cross-resistance to vincristine, vinblastine, adriamycin, actinomycin D, and puromycin; however, at the highest levels of colchicine resistance, increased cross-resistance to other drugs was not observed. There was no major change in protein synthesis or alteration in protein phosphorylation or [14C]glucosamine labeling patterns accompanying the development of multiple drug resistance as measured by analysis of metabolically labeled proteins on SDS gels. Cell-cell hybridization experiments showed that the colchicine-resistant and multiple drug-resistant phenotypes were incompletely dominant. In addition, colchicine resistance was found to segregate independently from resistance to other drugs in one somatic cell hybrid, suggesting that complex genetic loci are involved in the development of the multiple drug-resistant phenotype. These mutants should be useful for the study of the clinically important problem of multiple drug resistance in human cancer.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Literature cited
Bech-Hansen, N.T., Till, J.E., and Ling, V. (1976).J. Cell. Physiol. 88:23–32.
Beck, W.T., Mueller, T.J., and Tanzer, L.R. (1979).Cancer Res. 39:2070–2076.
Ling, V., and Baker, R.M. (1978).Somat. Cell Genet. 4:193–200.
Debenham, P.G., Kartner, N., Siminovitch, L., Riordan, J.R., and Ling, V. (1982).Mol. Cell. Biol. 2:881–889.
Juliano, R.L., and Ling, V. (1976).Biochim. Biophys. Acta 455:900–912.
Kartner, N., Riordan, J., and Ling, V. (1983).Science 221:1285–1288.
Riordan, J.R., and Ling, V. (1979).J. Biol. Chem. 254:12701–12705.
Biedler, J.L., and Peterson, R.H. (1981), In A.C. Sartorelli, J.S. Lazo, and J.R. Bertino, (eds.),Molecular Actions and Targets for Cancer Chemotherapeutic Agents, (Academic Press, New York), pp. 453–482.
Siegfried, J.M., Tritton, T.R., and Sartorelli, A.C. (1983).Eur. J. Cancer Clin. Oncol. 19:1133–1141.
Nelson-Rees, W.A., and Flandermeyer, R.R. (1976).Science 191:96–98.
Weisman, B., and Stanbridge, E.J. (1980).Cytogenet. Cell Genet. 28:227–239.
Davidson, R.L., and Gerald, P.L. (1977).Methods Cell Biol. 15:325–338.
Kaufman, R.J., Brown, P.C., and Schimke, R.T. (1979).Proc. Natl. Acad. Sci. U.S.A. 76:5669–5673.
Bonner, W.M., and Laskey, R.A. (1974).Eur. J. Biochem. 46:83–88.
Ling, V., and Thompson, L.H. (1974).J. Cell. Physiol. 83:103–116.
Weiss, M.C., and Ephrussi, B. (1966).Genetics 54:1095–1109.
Dolmick, B.J., Berenson, R.J., Bertino, J.R., Kaufman, R.J., Nunberg, J.H., and Schimke, R.T. (1979).J. Cell. Biol. 83:394–402.
Roninson, I.B. (1983).Nucleic Acid Res. 11:5413–5431.
Roninson, I.B., Abelson, H.T., Housman, D.E., Howell, N., and Varshavsky, A. (1984).Nature 309:626–628.
Beck, W.T., and Cirtain, M.C. (1982).Cancer Res. 42:184–189.
Schimke, R.T., Brown, P.C., Kaufman, R.J., McGrogan, M., and Slate, D.L. (1980).Cold Spring Harbor Symp. Quant. Biol. 45:785–797.
Richert, N., Akiyama, S., Shen, D.-W., Gottesman, M.M., and Pastan, I. (1985).Proc. Natl. Acad. Sci. U.S.A. (in press).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Akiyama, Si., Fojo, A., Hanover, J.A. et al. Isolation and genetic characterization of human KB cell lines resistant to multiple drugs. Somat Cell Mol Genet 11, 117–126 (1985). https://doi.org/10.1007/BF01534700
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01534700