@misc{oai:repo.qst.go.jp:00069754, author = {Nishimura, Mayumi and Imaoka, Tatsuhiko and Daino, Kazuhiro and Kakinuma, Shizuko and Shimada, Yoshiya and 西村 まゆみ and 今岡 達彦 and 臺野 和広 and 柿沼 志津子 and 島田 義也}, month = {May}, note = {Purpose Recent increase of breast cancer, in accordance with lifestyle changes, indicates that environmental factors greatly affect its development. The etiology includes ionizing radiation and chemicals in foods. Since cancer is induced by their combination in our ordinary life, it is important to delineate the mode and mechanism of combined effects of these agents. We aimed to address the issue on the modulating effect of radiation on rat mammary chemical carcinogenesis. Methods SD rats were exposed to either gamma-rays (0.5, 1, 2Gy), N-methyl-N-nitrosourea (MNU, 40 mg/kg), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP, 10x 40 mg/kg) or their combinations. Induced mammary carcinomas were examined for Hras mutation, genome-wide loss of heterozygosity (LOH) and promoter methylation of the Slc7a10 gene. Results The number of mammary carcinomas per rat increased linearly as a function of the radiation dose. When radiation was combined with MNU or PhIP, the mode of induction was mostly additive except for the combination of PhIP with 0.5 or 1 Gy, which showed a synergy. Hras mutation was characteristic for MNU-induced carcinomas, while LOH was a feature of PhIP-induced carcinomas. The promoter region of Slc7a10 was heavily methylated in both MNU and PhIP carcinomas. Neither of these alterations was evident for radiation-induced carcinomas. Interestingly, co-exposure to radiation increased the frequency of MNU-induced Hras mutation but decreased PhIP-induced LOH frequency. Density of promoter methylation in carcinomas induced by PhIP, but not MNU, was also reduced by co-exposure to radiation. Conclusion Manifestation of carcinogen-specific mutations is influenced by the co-exposure to radiation., 2nd Asian Congress of Radiation Research}, title = {Influence of co-exposure to gamma-rays on the manifestation of MNU- or PhIP-induced mutations in rat mammary carcinomas}, year = {2009} }