Grosovsky A J, Little J B
Proc Natl Acad Sci U S A. 1985 Apr;82(7):2092-5. doi: 10.1073/pnas.82.7.2092.
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.
在持续的人类淋巴母细胞培养物中研究了6-硫鸟嘌呤抗性（6TGR）的诱导情况，这些培养物每天接受1、2.5、5或10拉德（1拉德 = 0.01戈瑞）的X射线照射，照射时间长达1个月。每5天采集样本以测定诱导突变频率。每天接受1 - 10拉德剂量的细胞显示出每拉德有0.069×10⁻⁶个6TGR细胞的突变频率，这与在单次急性照射中接受相同总辐射剂量的淋巴母细胞所测定的每拉德0.062×10⁻⁶个6TGR细胞的值几乎相同。每日小剂量照射的效应是累加的，这表明低至1拉德的剂量在人类淋巴母细胞中具有致突变性。当使用对三氟胸苷的抗性（表明胸苷激酶缺乏）作为突变标记时，观察到了类似的结果。当将6TGR频率与照射天数作图时，所有剂量组均观察到正线性斜率。将这些斜率值与以拉德/天为单位的X射线剂量作图，以构建1 - 10拉德的剂量 - 反应关系。在这个剂量范围内观察到突变频率呈线性增加，没有明显的阈值。这种线性增加的斜率为每拉德0.060×10⁻⁶个6TGR细胞。这些结果表明，对于人类淋巴母细胞，低剂量X射线的致突变风险可以通过从高剂量效应进行线性外推来准确估计。
