@misc{oai:repo.qst.go.jp:00069048, author = {Yamauchi, Kazumi and Kakinuma, Shizuko and Sudou, Satomi and Kito, Seiji and Oota, Yuki and Nohmi, Takehiko and Masumura, Kenichi and Nishimura, Mayumi and Shimada, Yoshiya and 山内 一己 and 柿沼 志津子 and 須藤 聡美 and 鬼頭 靖司 and 太田 有紀 and 能美 健彦 and 増村 健一 and 西村 まゆみ and 島田 義也}, month = {Jul}, note = {Carcinogenesis in human is considered as a result of the combined exposure to numerous environment factors. Little is known, however, about the mechanism of combined effect. Since thymic lymphoma has been studied as a good model of combined exposure, we attempted to about determine the influence of combined exposure to ionizing radiation and N-ethyl-N-nitrosourea (ENU) on mutation induction in thymus using B6C3F1 gpt-delta transgenic mice. Four to 5 weeks of age Mice were exposed weekly to whole body X irradiation at 0.2 or 1 Gy for 4 consective weeks, ENU at 200 ppm in drinking water or X-irradiation followed by ENU. Thereafter, genome DNA was prepared from thymus and examined for gpt-delta mutation assay. The results obtained were as follows; (1) ENU alone increased mutant frequency by 10-folds compared to untreated control, especially increased in G:C to A:T transition at non CpG sequence and A:T to T:A transversion mutation, and over 80% of mutans were clonally expanded, (2) unexpectedly, X-irradiation alone, either 0.2 Gy or 1 Gy, reduced mutant frequency, (3) combined exposure to 0.2 Gy with ENU dramatically suppressed mutation induction, specifically G to A transition, compared to ENU alone, (4) 1 Gy exposure, by contrast, enhanced mutant frequency by about 30-folds and appeared to accelerate clonal expansion of mutated cells. In conclusion, low dose (0.2 Gy) radiation suppressed clonal expansion and mutation induction by ENU, while high dose (1 Gy) enhanced and accelerated clonal expansion of mutated thymocytes, indicating that the mode of combined effect is dose dependent., 13th International Congress of Radiation Research}, title = {Differential effect of low and high dose X-rays on mutation induction by N-ethyl-N-nitrosourea in thymocytes of B6C3F1 gpt-delta mice}, year = {2007} }