@article{oai:repo.qst.go.jp:00044128,
 author = {Imaoka, Tatsuhiko and Nishimura, Mayumi and Teramoto, Ayako and Nishimura, Yukiko and Ootawara, Masami and Osada, Harumi and Kakinuma, Shizuko and Maekawa, Akihiko and Shimada, Yoshiya and 今岡 達彦 and 西村 まゆみ and 寺本 彩子 and 西村 由希子 and 太田原 雅美 and 長田 春美 and 柿沼 志津子 and 島田 義也},
 issue = {2},
 journal = {International Journal of Cancer},
 month = {Feb},
 note = {Humans are continually exposed to various environmental carcinogens. Cancers may arise as a result of exposure to carcinogenic chemicals, ionizing radiation or a combination thereof. However, the mechanism of combined carcinogenesis has been only deduced from oncogenic actions of individual agents. Here, we analyzed experimental mammary carcinogenesis caused by a combination of radiation and a chemical carcinogen, 1-methyl-1-nitrosourea (MNU). Seven-week-old female Sprague-Dawley rats were divided into four groups: control, gamma-irradiated (2 Gy), MNU-treated (40 mg/kg, i.p.), and combined treatment of radiation with subsequent MNU after three days. Rats with palpable tumors were sacrificed at 50 weeks of age to collect tumors for histological typing and mutational analysis of the H-ras gene codon 12. The combined treatment induced adenocarcinomas, but not fibroadenomas, more efficiently than radiation or MNU alone. The H-ras mutation was not seen in radiation-induced carcinomas and was specific to MNU-induced carcinomas in individually treated groups. In the combined treatment group, H-ras-mutated, but not non-mutated, tumors were more frequent and developed significantly earlier than in the MNU-treated group. Significantly higher numbers of cells were stained for activated c-Myc protein in  -ray- and combined treatment-induced cancers than in MNU-induced cancers. These results indicate that combined exposure to the two carcinogens elicits an unexpected cooperativity in which pre-irradiation enhances mammary carcinogenesis predominantly through the oncogenic pathway involving H-ras, possibly by synergism with c-Myc activation.},
 pages = {187--193},
 title = {Cooperative induction of rat mammary cancer by radiation and 1-methyl-1-nitrosourea via the oncogenic pathways involving c-Myc activation and H-ras mutation},
 volume = {115},
 year = {2005}
}