@misc{oai:repo.qst.go.jp:00069062,
 author = {Kakinuma, Shizuko and Amasaki, Yoshiko and Yamauchi, Kazumi and Nishimura, Mayumi and Imaoka, Tatsuhiko and Shimada, Yoshiya and 柿沼 志津子 and 甘崎 佳子 and 山内 一己 and 西村 まゆみ and 今岡 達彦 and 島田 義也},
 month = {Jul},
 note = {We are living in the environment with numerous natural and man-made radiation and chemicals. Cancer development in human is considered as a result of interaction with these factors. But, the quantitative assessment and mechanistic understanding of combined effects of radiation and chemical carcinogens are still insufficient. The aim of this study is to elucidate the mode and mechanism of the combined effect of X-rays with N-ethyl-N-nitrosourea (ENU) on mouse thymic lymphoma, especially at low or threshold dose range. 
We previously showed that the dose-response curve for X-ray- or ENU?induced thymic lymphoma had threshold dose. X-ray-induced thymic lymphoma was characteristic for frequent inactivation of Ikaros caused by transcriptional silencing, unusual splicing, point mutation and small insertion, most of which were associated with loss of heterozygosity (LOH). In contrast, ENU-induced tumors had point mutations of Ikaros without LOH.  In combination, X-irradiation followed by ENU exposure resulted in the synergistic effect at high dose, while the effect was antagonistic at low or threshold dose. When the order of exposure was reversed, i.e., ENU followed by X-rays, the mode of combined exposure was additive at any doses. Molecular analysis demonstrated that Ikaros mutation in thymic lymphoma after X-irradiation followed by ENU at high doses was predominantly point mutation without LOH (ENU-type).  But, after reverse treatment, mutation spectrum of Ikaros was similar to that observed in thymic lymphoma after X-ray exposure alone. It is concluded that the mode of combined effect is dependent upon the treatment order and the dose of carcinogens., 13th International Congress of Radiation Research},
 title = {Combined effects of ionizing radiation and N-ethyl-N-nitrosourea in murine thymic lymphoma},
 year = {2007}
}