Tsyusko O, Yi Y, Coughlin D, Main D, Podolsky R, Hinton T G, Glenn T C
Savannah River Ecology Laboratory, University of Georgia, Aiken, SC 29802, USA.
Comp Biochem Physiol C Toxicol Pharmacol. 2007 Feb;145(1):103-10. doi: 10.1016/j.cbpc.2006.08.010. Epub 2006 Sep 3.
Radiation has been shown to increase mutation frequencies at tandem repeat loci by indirect interactions of radiation with DNA. We studied germline mutations in chronically exposed Japanese medaka (Oryzias latipes) using microsatellite loci. After screening 26 randomly selected loci among unirradiated parents and their 200 offspring, we selected seven highly mutable loci (0.5-1.0 x 10(-2) mutants per locus per gamete) and two bonus loci for further study. To determine if radiation exposure increases mutation frequencies in these loci, medaka were chronically irradiated from subadults through maturation at relatively low dose rates of 68 mGy/d. Total doses for males and females were 10.4 and 3 Gy, respectively. The mean number of mutations for the offspring of exposed families (0.149+/-0.044) was significantly higher (P=0.018) than for control families (0.080+/-0.028), indicating induction of germline mutations from chronic irradiation. This increase in the microsatellite mutation rate is greater than expected from direct interaction of radiation with DNA, suggesting indirect, untargeted mechanism(s) for mutations. This study identified microsatellite loci with a high mutational background in medaka, variation among loci and families as important variables, and demonstrated the usefulness of this fish model for studying radiation-induced germline mutations.
辐射已被证明可通过辐射与DNA的间接相互作用增加串联重复基因座处的突变频率。我们使用微卫星基因座研究了长期暴露的日本青鳉（Oryzias latipes）的生殖系突变。在对未受辐射的亲代及其200个后代中随机选择的26个基因座进行筛选后，我们选择了7个高变基因座（每个配子每个基因座有0.5 - 1.0×10⁻²个突变体）和2个额外基因座进行进一步研究。为了确定辐射暴露是否会增加这些基因座的突变频率，青鳉从亚成体到成熟阶段以68 mGy/d的相对低剂量率进行长期辐照。雄性和雌性的总剂量分别为10.4 Gy和3 Gy。暴露组家庭后代的平均突变数（0.149±0.044）显著高于对照组家庭（0.080±0.028）（P = 0.018），表明慢性辐照可诱导生殖系突变。微卫星突变率的这种增加大于辐射与DNA直接相互作用所预期的，这表明存在间接的、非靶向的突变机制。本研究确定了青鳉中具有高突变背景的微卫星基因座，基因座和家庭之间的变异是重要变量，并证明了这种鱼类模型在研究辐射诱导的生殖系突变方面的有用性。
