Induction of Congenital Anomalies in the Progeny After Germ Cell Exposure to Radiation and Chemicals.

众所周知，辐射和化学物质会在高等动植物中产生可见的致命突变。特别是在小鼠身上，已经通过特定的位点方法等做了大量的工作，但用这些已建立的方法来检测各种化学物质需要大量的动物。最近，野村证券发现，父母暴露在辐射中会导致下一代小鼠先天性畸形。此外，在F_1代中发现的诱发畸形与人类相似。本项目的实验结果总结如下：(1)先天性畸形胚系突变检测方法的建立及其在化学制品中的应用：ENU、DMBA、4NQO和X射线孕前处理均可引起F_1代显著的先天性畸形发生率。与X射线相比，精原细胞阶段对ENU的敏感性高于减数分裂后阶段，因为它处于特定的基因突变。(2)生发突变检测功能缺陷：亲代暴露于ENU和X射线导致F_1胎儿呼吸窘迫的显著发生率，(4)精子受精能力的损害：极低剂量的AS和LAS干扰了人和小鼠精子对金黄地鼠卵的受精能力。(5)WHO建议：采用导致F_1代先天畸形的胚系改变作为检测遗传危险的方法。(6)未来问题：应进行临床和流行病学调查。功能缺陷在人类群体中将变得更加重要。

Radiation and chemicals are well known to produce visible and lethal mutations in higher plants and animal. Especially, extensive works have been done by specific loci method, etc. In mice, but large numbers of animals are necessary to test a variety of chemicals by these established methods. Recently, Nomura found that parental exposure to radiation can cause congenital malformations in the next generation in mice. Furthermore, induced malformations in F_1 offspring were similar to those found in humans. Experimental results obtained in the term of this project were summa-rized as follows.(1) Establishment of a method to detect germ-line mutation causing congenital malformation and its application to chemicals : Preconceptional treatment with ENU, DMBA and 4NQO as well as X-rays induced a significant incidence of congenital malformations in the F_1 offspring. In contrast to X-rays, spermatogonial stage was more sensitive to ENU than post-meiotic stages as it was in the specific locus mutation.(2) Detection of functional defects by germinal mutation : Parental exposure to ENU and X-rays caused a significant incidence of respiratory distress in F_1 fetuses, and a half of them were not accompanied with morphological malformations.(3) Heritability of induced malformations in the offspring : Dwarfism and tail anomalies inherited as a dominant trait with reduced expressivity.(4) Damage to fertilization capacity of the sperm : Very low doses of AS and LAS interrupted fertilization capacity of the human and mouse sperm to golden hamster eggs.(5) WHO recommendation : Germ-line alterations causing congenital malformation in F_1 offspring was adopted as a method to detect genetic hazards.(6) Future problems : Clinical and epidemiological survey should be performed. Functional defects will become more important in human population.