Measurement of mutant frequency in T-cell receptor (TCR) gene by flow cytometry after X-irradiation on EL-4 mice lymphoma cells

J Toxicol Sci. 2007 Oct;32(4):377-86. doi: 10.2131/jts.32.377.

Abstract

It is well known that somatic mutations are induced by ionizing irradiation. We have previously reported the measurement of mutant frequency (MF) on the T-cell receptor (TCR) gene in mouse T-lymphocytes after irradiation by flow cytometry. In this study, we developed an in vitro system using murine EL-4 lymphoma cells and observed frequency of cells defective in TCR gene expression after exposure to ionizing irradiation. EL-4 cells were stained with fluorescein-labeled anti-CD4 and phycoerythrin-labeled anti-CD3 antibodies. They were analyzed with a flow cytometer to detect mutant EL-4 cells lacking surface expression of TCR/CD3 complexes which showed CD3-, CD4+ due to a somatic mutation at the TCR genes. Mutant cells could be observed at 2 days after 3 Gy irradiation. MF of EL-4 cells was 6.7x10(-4) for 0 Gy and the value increased to the maximum level of 39x10(-4) between 4 and 8 days after 3 Gy irradiation and these data were found to be best fitted by a linear-quadratic dose-response model. After the peak value the TCR MF gradually decreased with a half-life of approximately 3.2 days. We also examined the hprt mutant frequencies at seven days after irradiation and the cytokinesis-blocked micronucleus frequency at 20 hrs after irradiation. The frequencies of hprt mutation and micronuclei were found to be best fitted by a linear-quadratic dose-response model and a linear dose-response model, respectively. The method to detect mutation on TCR gene is quick and easy in comparison with other methods and is considered useful for the mutagenicity test.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Survival / radiation effects
  • Dose-Response Relationship, Radiation
  • Flow Cytometry
  • Gene Expression / radiation effects*
  • Hypoxanthine Phosphoribosyltransferase / genetics
  • Mice
  • Micronucleus Tests
  • Mutation*
  • Receptors, Antigen, T-Cell / genetics*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / radiation effects*
  • X-Rays / adverse effects

Substances

  • Receptors, Antigen, T-Cell
  • Hypoxanthine Phosphoribosyltransferase