@misc{oai:repo.qst.go.jp:00070715,
 author = {Hirano, Shinobu and Kakinuma, Shizuko and Amasaki, Yoshiko and Nishimura, Mayumi and Imaoka, Tatsuhiko and Fujimoto, Shinji and Hino, Okio and Shimada, Yoshiya and 坂入 しのぶ and 柿沼 志津子 and 甘崎 佳子 and 西村 まゆみ and 今岡 達彦 and 島田 義也},
 month = {Mar},
 note = {Cancer risk of radiation in humans is considered to result from simultaneous exposure to radiation and chemicals carcinogens. But its molecular mechanisms is insufficient. In this study, using a mouse thymic lymphoma (TL) model synergistically induced by simultaneous exposure to X-rays and N-ethyl-N-nitrosourea (ENU) at sub-carcinogenic doses, we analyzed the mutation of the TL-associated genes Ikaros, Notch1, p53, and Kras.
Beginning at 4 weeks of age, female B6C3F1 mice were weekly exposed to X-rays at 0.8, 1.0 or 1.2 Gy and given ENU at 100 or 200 ppm for 4 consecutive weeks at the same time. Collected TLs were examined for molecular analyses.
The point mutation frequency of Ikaros was 47% for simultaneous exposure, whereas 13% and 0% for X-ray and ENU exposure, respectively. These were mostly G:C > A:T at non-CpG sites and T:A > C:G characteristic of ENU mutagenesis. About half of the point mutations were accompanied by loss of heterozygosity (LOH), typical of X-rays. The remains did not include LOH, suggesting dominant-negative mutations. Abnormality frequency of Notch1 was high regardless of the treatment, but those of p53 and Kras were low. Importantly, the frequency of TLs containing mutations in both Ikaros and Notch1 increased after simultaneous exposure. Thus, in TL after simultaneous exposure, Ikaros is a critical target and inactivated by ENU-induced point mutations and X-ray-induced LOH. Furthermore, concomitant alterations of TL-associated genes may contribute to extreme lymphomagenesis., 順天堂大学大学院医学研究科3年次ポスターセッション},
 title = {Ikaros is a critical target during simultaneous exposure to X-rays and N-ethyl-N-nitrosourea in mouse T-cell lymphomagenesis},
 year = {2012}
}