Genetic effects of combined gamma-rays-ENU treatments as revealed by the Medaka specific-locus test system

青鳉特异性基因座测试系统揭示了伽马射线与 ENU 联合治疗的遗传效应

基本信息

批准号：
06454635
负责人：
SHIMA Akihiro
金额：
$ 4.86万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06454635/
关键词：
Medaka Germ cell Mutagenesis gamma-rays ENU Additive Synergistic

项目摘要

On the basis of the data accumulated during the last ten years by examining more than 900,000 embryos corresponding to approx.2,400,000 loci, we consider that the basis of the Medaka specific-locus test system has been well setablished. Because the treatment so far adopted in our study was exposure to a single agent including gamma-rays, ENU or reactor radiation, we decided to precede to examine the genetic effects of combined gamma-rays-- ENU treatments by using the Medaka specific-locus test system.Fifty wild type adult males of the Sakura strain were exposed at room temperature to 4.75 Gy of gamma-rays followed 20 to 30 min.later by an exposure to 0.5mM ENU for 2 hours at 27ﾟC.Each treated male was mated to a female of our tester strain AA2. Extensive sequential collection of embryos was done from the first day through 30 days after the combined treatments. The genetic endpoints examined were dominant lethals, total mutations and viable mutations. Observed results were compared with … More those already obtained for separate treatments with gamma-rays or ENU.The additivity or synergism was tentatively calculated on the basis of fold-increase over spontaneous rates [90% upper confidence limit/lower limit], which were 0.0557 [0.0566/0.0550]/gamete, 3.79 [5.51/2.61]x10^<-5>/locus, and 4.17 [12.6/1.38]x 10^<-6>/locus, respectively, for dominant lethals, total mutation and viable mutation.The observed dominant lethal rates for sperm, spermatids, spermatocytes, differentiating spermatogonia and stem spermatogonia were, respectively, 0.584 [0.605/0.565], 0.550 [0.563/0.537], 0.394 [0.413/0.375], 0.123 [0.134/0.114], and 0.0493 [0.0525/0.464]. The observed values for the postmeiotics including sperm, spermatids and spermatocytes were higher than the value expected on the basis of simple additivity, but lower than that expected on the basis of synergism. With regard to the premeiotics including differentiating and stem spermatogonia, however, the observed dominant lethal rates were lower than both the two expected rates. The situation between the observed and expected rates of total mutations was almost the same as that for dominant lethals. The observed viable mutation frequencies for the postmeiotics as well as the premeiotics were not significantly different from that expected on the basis of simple additivity, the rates expected on the basis of synergism being almost 10-fold higher than the previous two sets of rates. The ratio of total mutation rate to viable one changed from radiation-type to ENU-type with changes from postmeitic exposure to premeiotic exposure. Less

根据过去十年来累积的数据，检查了900,000多个与大约2,400,000个基因座相对应的胚胎，我们认为MEDAKA特异性测试系统的基础已得到很好的设定。因为我们研究到目前为止采用的治疗方法是暴露于包括γ射线，ENU或反应器辐射在内的单一药物，我们决定在检查γ-射线合并治疗的遗传效应之前，通过使用Medaka特异性 - 洛克萨斯测试系统的遗传效应。 ENU在27°C. C. EACH治疗的雄性与我们的测试师AA2菌株的女性伴侣。从合并治疗后的第一天到30天完成了胚胎的广泛顺序收集。所检查的遗传终点是主要致死性，总突变和可行的突变。将观察到的结果与……更多的结果进行了比较。更多那些已经获得γ射线或ENU的单独处理的结果。添加性或协同作用是根据赞助率的折叠率（90％上限置信度限制/下部下限）进行的，该折叠率是0.0557 [0.0557 [0.0566/0.0550]/GAMETE，3.79 [5.51] [5.51] [5.51] [5.51]，<5.51/2.61]， [12.6/1.38] X 10^<-6>/基因座，分别用于主要致死性，总突变和可行的突变。精子，精子，精子细胞，精子细胞和STEM精子的主体率分别分别为0.584 [0.584 [0.605/0.565] [0.563/0.537]，0.394 [0.413/0.375]，0.123 [0.134/0.114]和0.0493 [0.0525/0.464]。观察到的倍年后的值，包括精子，精子和精子细胞高于基于简单添加的预期值，但基于协同作用的预期高于预期。然而，关于包括区分和茎精子症在内的前毒素，观察到的主要致命率低于两个预期率。观察到的总突变速率和预期速率之间的情况几乎与主要致死剂相同。观察到的寿命后生存的突变频率以及前二次的突变频率与预期的简单添加没有显着差异，基于协同作用，预期的速率几乎比前两组速率高10倍。总突变率与可行的比率从辐射类型到ENU型，随着辉长岩的变化而变化为前期暴露。较少的