Evidence for linear response for the induction of mutations in human cells by x-ray exposures below 10 rads

The induction of 6-thioguanine resistance (6TGR) was studied in continuous human lymphoblast cultures exposed to daily x-ray doses of 1, 2.5, 5, or 10 rads (1 rad = 0.01 gray) for periods up to 1 month. Samples were taken every 5 days for determinations of induced mutation frequency. Cells receiving daily doses of 1-10 rads showed a mutation frequency of 0.069 X 10(-6) 6TGR cell per rad, virtually identical to the value of 0.062 X 10(-6) 6TGR cell per rad determined for lymphoblasts receiving the same total dose of radiation in a single acute exposure. The effects of small daily fractions were additive, suggesting that doses as small as 1 rad are mutagenic in human lymphoblasts. Similar results were observed when resistance to trifluorothymidine, indicative of thymidine kinase deficiency, was used as a mutational marker. When 6TGR frequency was plotted against days of irradiation, a positive linear slope was observed for all dose groups. The values of these slopes were plotted against x-ray dose in rads/day to construct a dose-response relationship for 1-10 rads. A linear increase in mutation frequency was observed over this dose range, with no apparent threshold. The slope of this linear increase was 0.060 X 10(-6) 6TGR cell per rad. These results suggest that, for human lymphoblasts, the mutagenic risk of low doses of x-rays can be accurately estimated by linear extrapolation from high-dose effects.