Mitogenic stimulation may induce an anti-mutagenic repair system in human lymphocytes

The effect of mitogenic stimulation prior to X-irradiation was studied in human lymphocytes using a cloning technique. The hypoxanthine phosphoribosyltransferase locus was monitored and mutant cells were selected by their ability to form a clone in the presence of 6-thioguanine. Survival and mutagenesis were studied for cells irradiated before phytohaemagglutinin (PHA) stimulation and 1-7 days after PHA stimulation. Prior mitogenic stimulation had no effect on the decreasing survival observed with increasing X-ray dose. The mean mutation frequency of unirradiated cells ranged from 1.8 x 10(-6) to 3.3 x 10(-6). Cells irradiated and then stimulated with PHA showed an increase in mutation frequency with increasing dose of X-rays, up to 9.5 x 10(-5) after 400 rad, but mitogenic stimulation with PHA on days 2 or 3 before irradiation completely, and on days 1, 5 or 7 almost completely, prevented induction of mutations by 300 rad. These results suggest that mitogenic stimulation activates an anti-mutagenic system which prevents pre-mutational lesions produced by X-irradiation being transformed into mutations. The lack of effect of PHA stimulation on survival suggests that the types of damage leading to mutations and lethality are different.