The response of gamma-H2AX in human lymphocytes and lymphocytes subsets measured in whole blood cultures

Int J Radiat Biol. 2009 Apr;85(4):369-76. doi: 10.1080/09553000902781147.

Abstract

Purpose: To assess the use of phosphorylated histone H2AX protein (gamma-H2AX) in human blood leukocytes as a rapid screening tool for radiation biodosimetry using a method that examines the characteristics of gamma-H2AX phosphorylation in a variety of lymphocyte subsets following exposure to radiation.

Materials and methods: Human peripheral blood exposed to 0-10 Gy of (137)Cs irradiation and cultured for 0-48 h was analysed using a rapid whole blood flow cytometry assay to measure gamma-H2AX phosphorylation in different lymphocyte subpopulations.

Results: Lymphocyte subsets displayed a similar linear dose response relationship, although cluster of differentiation 4(+) (CD4(+)) and CD8(+) lymphocytes were found to express H2AX phosphorylation on the order of 1.5 times higher than CD19(+) lymphocytes. Phosphorylation of all lymphocyte subsets reached a maximum at 1.5 h and had essentially returned to baseline levels 24 h post-exposure.

Conclusions: Differences in the expression level of gamma-H2AX between lymphocyte subsets were minimal. The usefulness of this assay for radiation biodosimetry is hampered by its relatively quick lifetime kinetics and large inter-individual variation. Therefore, it could only be useful if samples were obtained within 24 h of exposure. Even in this situation, the assay could only be used as an indicator of exposure and not a dosimeter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cells, Cultured
  • Dose-Response Relationship, Radiation
  • Female
  • Flow Cytometry
  • Histones / blood*
  • Histones / metabolism
  • Humans
  • Lymphocyte Subsets / metabolism*
  • Lymphocyte Subsets / radiation effects*
  • Lymphocytes / metabolism*
  • Lymphocytes / radiation effects*
  • Male
  • Mass Casualty Incidents
  • Middle Aged
  • Phosphorylation
  • Radiometry / methods*
  • Time Factors

Substances

  • H2AX protein, human
  • Histones