Discovery of numerous clusters of spontaneous mutations in the specific-locus test in mice necessitates major increases in estimates of doubling doses
Discovery of numerous clusters of spontaneous mutations in the specific-locus test in mice necessitates major increases in estimates of doubling doses
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DOI：
10.1023/a:1017070722428
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发表时间：
1998-01-01
期刊：
影响因子：
1.5
通讯作者：
Selby, PB
中科院分区：
文献类型：
--
作者：
Selby, PB
快速识别突变的精确度和该方法的广泛应用，使得小鼠特定基因座实验的结果对于估计倍增剂量尤为重要，倍增剂量是指辐射暴露导致的突变频率等于每代人的总自发突变频率。由于性腺嵌合体及其发生机制，每代人发生新的自发突变的频率比人们认为的要高得多。虽然与理解这一现象有关的许多新出现的不确定因素还需要一段时间才能解决，但考虑到已知的情况，将低剂量率照射X和伽马辐射的倍增剂量从1GY提高到5GY已经是合理的。这样做将使双倍剂量法所做的风险估计减少五倍。由于化学诱变剂的倍增剂量也是通过每代人的总自发突变频率除以每单位化学物质暴露的诱导突变频率来计算的，如果基于特定基因座数据，化学物质的遗传风险也被大大高估了。
Both the precision with which mutations can be quickly identified and the extensive application of the method make results from specific-locus experiments in mice especially important for estimating the doubling dose, which is the radiation exposure that induces a mutation frequency equal to the total spontaneous mutation frequency per generation. Because of gonadal mosaicism and the mechanism by which it occurs, the frequency with which new spontaneous mutations occur per generation is much higher than has been thought. While it will be some time before many of the newly-apparent uncertainties related to understanding this phenomenon can be resolved, consideration of what is known suggests that it would already be reasonable to raise the doubling dose from 1 to 5 Gy for low-dose-rate exposures to X and gamma radiation. Doing so would reduce risk estimates made by the doubling-dose method fivefold. Because the doubling dose for chemical mutagens is also calculated by division of the total spontaneous mutation frequency per generation by the induced mutation frequency per unit of chemical exposure, hereditary risks for chemicals have also been considerably overestimated if they are based on specific-locus data.