@article{oai:repo.qst.go.jp:00048441,
 author = {Nakayama, Takafumi and Sawai, Tomoko and Masuda, Ikuko and Kaneko, Shinya and Yamauchi, Kazumi and Blyth, Benjamin and Shimada, Yoshiya and Tachibana, Akira and Kakinuma, Shizuko and 中山 貴文 and 澤井 知子 and 益田 郁子 and 山内 一己 and Ｂｌｙｔｈ Ｂｅｎｊａｍｉｎ and 島田 義也 and 立花 章 and 柿沼 志津子},
 issue = {8},
 journal = {Environmental and Molecular Mutagenesis},
 month = {Oct},
 note = {DNA mutations play a crucial role in the origins of cancer, and the clonal expansion of mutant cells is one of the fundamental steps in multistage carcinogenesis. In this study, we correlated tumor incidence in B6C3F1 mice during the period after exposure to N-ethyl-N-nitrosourea (ENU) with the persistence of ENU-induced mutant clones in transgenic gpt delta B6C3F1 mice. The induced gpt mutations afforded no selective advantage in the mouse cells and could be distinguished by a mutational spectrum that is characteristic of ENU treatment. The gpt mutations were passengers of the mutant cell of origin and its daughter cells and thus could be used as neutral markers of clones that arose and persisted in the tissues. Female B6C3F1 mice exposed for 1 month to 200 ppm ENU in the drinking water developed early thymic lymphomas and late liver and lung tumors. To assay gpt mutations, we sampled the thymus, liver, lung, and small intestine of female gpt delta mice at 3 days, 4 weeks, and 8 weeks after the end of ENU exposure. Our results reveal that, in all four tissues, the ENU-induced gpt mutations persisted for weeks after the end of mutagen exposure. Clonal expansion of mutant cells was observed in the thymus and small intestine, with the thymus showing larger clone sizes. These results indicate that the clearance of mutant cells and the potential for clonal expansion during normal tissue growth depends on tissue type and that these factors may affect the sensitivity of different tissues to carcinogenesis.},
 pages = {592--606},
 title = {Tissue-specific and time-dependent clonal expansion of ENU-induced mutant cells in gpt delta mice.},
 volume = {58},
 year = {2017}
}