51. Molecular Analysis of the Germ-line Mutation Induced by Ionizing Radiation

Masatake Yamauchi, Satsuki Tsuji, Toshiyuki Saito, Tada-aki Hori, Yoshiya Shimada, Yoko Ishii, Mayumi Nishimura, Toshiaki Ogiu, Masanori Okamoto, and Tsuneya Matsumoto

Keywords: radiation, germ-line mutation, mice, scid, genetic instability

Germ-line mutation induced by ionizing radiation is suspected as a cause for the increased risk of developing cancers in successive generations. However, no increased risk has been observed among children born to atomic bomb survivors exposed at Hiroshima or Nagasaki.

Our three-year project has aimed at investigating the germ-line mutation induced by ionizing radiation using experimental mouse strains, with or without a genetic background that affects radio sensitivity.

The Pc-1 locus is known as a hypervariable minisatellite. In the first fiscal year of the project, we analyzed the Pc-1 locus to detect the spontaneous level of the germ-line mutation (genetic instability). Molecular analysis of the Pc-1 locus in the offspring of CB17 revealed that the spontaneous mutation rate was about 5% under the ordinary breeding conditions used in our institute. The mutation frequency obtained here was 50% lower than that previously reported by another research group. This suggested that the spontaneous germ-line mutation might be considerably affected by the mouse strain and the breeding conditions. The offspring between CB17 and scid showed higher genetic instability compared to the parental strain, CB17, suggesting the scid mutation affects the genetic instability at the Pc-1 locus.

In the second fiscal year, we made modifications in experimental procedures to enhance the accuracy of the molecular analysis, and obtained a number of materials for statistical analysis of the germ-line mutation induced by irradiation. However, the scientific council of our institute declared that the modifications in the experimental procedures on the half way should have not been made, and decided the project should not be extended to the third fiscal year. The materials have been left unanalyzed.