@inproceedings{oai:repo.qst.go.jp:00054083, author = {Yamauchi, Kazumi and Kakinuma, Shizuko and Nakata, Akifumi and Imaoka, Tatsuhiko and Takabatake, Takashi and Nishimura, Mayumi and Shimada, Yoshiya and 山内 一己 and 柿沼 志津子 and 中田 章史 and 今岡 達彦 and 高畠 貴志 and 西村 まゆみ and 島田 義也}, book = {Radiation Health Risk Sciences : Proceedings of the First International Symposium of the Nagasaki University Global COE Program "Global Strategic Center for Radiation Health Risk Control"}, month = {}, note = {Carcinogenesis in humans is thought to result from exposure to numerous environmental factors. Little is known, however, about how these different factors work in combination to cause cancer. Mouse thymic lymphoma is a good model for research on radiation and chemical carcinogenesis. We examined here the occurrence of thymic lymphoma and mutation induction following exposure to both X-rays and N-ethyl-N-nitrosourea (ENU) in B6C3F1 mice. Mice were exposed weekly to whole body X-irradiation (0.2 or 1.0 Gy per each exposure) for 4 consecutive weeks, ENU (200 ppm) in the drinking water for 4 weeks, or X-irradiation followed by ENU treatment. The incidence of lymphoma after 0.2 and 1.0 Gy were 0 and 10%, respectively. ENU treatment induced lymphoma in 20% of exposed mice. When ENU was combined with 1.0 Gy, lymphoma incidence increased up to 94%, showing a synergistic effect. In contrast, combination of ENU with 0.2 Gy resulted in a decrease in lymphoma incidence, i.e., an antagonistic effect. Mutation frequency of the reporter transgene gpt after ENU exposure alone increased by 10-fold compared to untreated controls. Combined exposure of ENU with 0.2 Gy X-rays dramatically decreased mutant frequency. In contrast, 1.0 Gy X-rays combined with ENU further enhanced mutant frequency and accelerated clonal expansion of mutated cells. In conclusion, mutagenic and carcinogenic effect of combined exposure of X-rays with ENU is dose dependent.}, pages = {227--231}, publisher = {Springer}, title = {Combined Effect of Ionizing Radiation and N-Ethyl-N-Nitrosourea on Mutation Induction and Lymphoma Development}, year = {2008} }