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Induction of somatic mutations by low-dose X-rays: the challenge in recognizing radiation-induced events

机译:低剂量X射线诱导体细胞突变:识别辐射诱发事件的挑战

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摘要

It is difficult to distinguish radiation-induced events from spontaneous events during induction of stochastic effects, especially in the case of low-dose or low-dose-rate exposures. By using a hypersensitive system for detecting somatic mutations at the HPRT1 locus, we investigated the frequency and spectrum of mutations induced by low-dose X-rays. The mutant frequencies induced by doses of >0.15 Gy were statistically significant when compared with the spontaneous frequency, and a clear dose dependency was also observed for mutant frequencies at doses of >0.15 Gy. In contrast, mutant frequencies at doses of <0.1 Gy occurred at non-significant levels. The mutation spectrum in HPRT-deficient mutants revealed that the type of mutations induced by low-dose exposures was similar to that seen in spontaneous mutants. An apparent change in mutation type was observed for mutants induced by doses of >0.2 Gy. Our observations suggest that there could be a critical dose for mutation induction at between 0.1 Gy and 0.2 Gy, where mutagenic events are induced by multiple DNA double-strand breaks (DSBs). These observations also suggest that low-dose radiation delivered at doses of <0.1 Gy may not result in DSB-induced mutations but may enhance spontaneous mutagenesis events.
机译:在诱发随机效应期间,很难将辐射诱发的事件与自发事件区分开,尤其是在低剂量或低剂量率照射的情况下。通过使用超敏系统检测HPRT1基因座处的体细胞突变,我们研究了低剂量X射线诱导的突变的频率和光谱。与自发频率相比,剂量大于0.15 Gy的突变频率具有统计学意义,并且剂量大于0.15 Gy的突变频率也具有明显的剂量依赖性。相反,剂量小于0.1 Gy的突变频率发生在非显着水平。 HPRT缺陷型突变体的突变谱显示,低剂量暴露诱导的突变类型与自发突变体相似。对于> 0.2Gy的剂量诱导的突变体,观察到突变类型的明显变化。我们的观察结果表明,可能需要在0.1 Gy和0.2 Gy之间进行突变诱导的关键剂量,其中诱变事件是由多个DNA双链断裂(DSB)诱导的。这些观察结果还表明,以小于0.1 Gy的剂量传递的低剂量辐射可能不会导致DSB诱导的突变,但可能会增强自发诱变事件。

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