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、致命的突变。特别是用特定位点法等方法做了大量的工作。在老鼠身上，但要用这些既定的方法测试各种化学物质，需要大量的动物。最近，野村发现，父母暴露在辐射中会导致下一代小鼠的先天性畸形。此外，F_1后代的诱导畸形与人类相似。现将项目期间的实验结果总结如下：(1)建立致先天性畸形的种系突变检测方法及其在化学药品中的应用：孕前用ENU、DMBA、4NQO以及x射线治疗可使F_1子代先天性畸形发生率显著升高。与x射线相比，精原阶段比减数分裂后阶段对ENU更敏感，因为它在特定的位点突变中。(2)生发突变检测功能缺陷：父母暴露于ENU和x射线下，F_1胎呼吸窘迫发生率显著，且半数胎儿未伴有形态畸形。(3)后代诱导畸形的遗传力：侏儒症和尾巴异常作为显性性状遗传，表达性降低。(4)对精子受精能力的损害：极低剂量的AS和LAS可破坏人和小鼠精子对金仓鼠卵的受精能力。(5) WHO推荐：采用生殖系改变导致的F_1子代先天性畸形作为检测遗传危害的方法。(6)今后面临的问题：开展临床和流行病学调查。功能缺陷将在人类中变得更加重要。

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.