@misc{oai:repo.qst.go.jp:00063580,
 author = {Ikeda, Megumi and Masumura, Kenichi and Sakamoto, Yasuteru and Bing, Wang and Nenoi, Mitsuru and Hayata, Isamu and Honma, Masamitsu and Nohmi, Takehiko and et.al and 池田 恵 and 増村 健一 and 坂元 康晃 and 王 冰 and 根井 充 and 早田 勇 and 能美 健彦},
 month = {Oct},
 note = {It is important to evaluate the combined effects of low–dose-rate or low-dose radiation with chemicals as humans are exposed to a variety of chemical agents. Here, we applied gpt delta transgenic genotoxicity assay to examine combined genotoxic effects of low-dose-rate radiation and 4-(methylnitrosamino)-1-(3-pyridy1)-1-butanone (NNK), the most carcinogenic tobacco-specific nitrosamine and a methylating agent, in the lung of mice. In this mouse model, base substitutions and deletions can be separately analyzed by gpt and Spi- selections, respectively. Female gpt delta mice were treated either with gamma-irradiation alone at a dose rate of 0.5, 1.0 or 1.5mGy/h for 22 h/day for 31 days or its combination with NNK at a dose of 2mg/mouse/day, i.p. for four consecutive days in the middle course of irradiation. In the gpt selection, the NNK treatments enhanced the mutation frequencies (MFs) significantly, but no obvious combined effects of gamma-irradiation were observable at any given radiation dose. In contrast, NNK treatments appeared to suppress the Spi- large deletions. In the Spi- selection, when NNK treatments were combined, the dose-response curve became bell-shaped where the highest radiation dose decreased substantially. These results suggest that NNK treatments may elicit an adaptive response that eliminates cells bearing radiation-induced double-strand breaks (DSBs) in DNA. We are currently examining the mechanisms underlying the apparent suppressive effects of methylating agent against radiation-induced DSBs with human cells in vitro., The 7th Japan-France Workshop on Radiation Biology},
 title = {gpt delta transgenic mice for in vivo genotoxicity assays: application for analysis of combined effects of radiation and chemicals},
 year = {2008}
}