@misc{oai:repo.qst.go.jp:00069756,
 author = {Hirano, Shinobu and Kakinuma, Shizuko and Amasaki, Yoshiko and Kowatari, Norie and Yamauchi, Kazumi and Nishimura, Mayumi and Imaoka, Tatsuhiko and Shimada, Yoshiya and 坂入 しのぶ and 柿沼 志津子 and 甘崎 佳子 and 古渡 礼恵 and 山内 一己 and 西村 まゆみ and 今岡 達彦 and 島田 義也},
 month = {May},
 note = {Purpose
It is well known that several oncogenes or tumor suppressor genes are mutated in carcinogen-induced tumors. However, available data are quite small about the accumulation of mutation after combined exposure to radiation and chemical carcinogens. In the present study, we aimed to determine the change in frequency and spectrum of Ikaros, p53 and Kras point mutations in thymic lymphomas of B6C3F1 mice, which were simultaneously exposed to X-rays and ENU.
Methods
Beginning at 4 weeks of age, a group of female B6C3F1 mice was weekly exposed to whole-body X irradiation at 0.2 0.4 0.8 and 1.0 Gy for 4 consecutive weeks and given N-ethyl-N-nitrosourea (ENU) in drinking water at 50, 100 and 200 ppm for 4 consecutive weeks at the same time. Collected lymphomas were examined for the mutations of Ikaros, p53 and Kras.
Result
The simultaneous exposure to X-rays and ENU increased thymic lymphoma incidence in a synergistic manner at high doses. TL samples circled with pink line was analyzed by sequencing. Ikaros and p53 mutation frequency significantly increased in a supra-additive manner, but, Kras mutation frequency showed not supra-additive in the simultaneous exposure. Increase in Ikaros mutation was ascribed in part to G to T/C base substitution, which were newly generated by combined exposure. In addition, T to C and G to A substitution were supra-additive compared to single exposure. Point mutation of G to C and T to C/G were newly generated in p53. The mutations of Ikaros and p53 distributed mainly in the DNA binding domain. And the distribution of mutation was very wide in simultaneous exposure. Whereas, most mutated position of Kras was G to A at codon 12. Newly generated and supra-additive mutation were not detected in Kras.
Conclusion
The frequency of point mutation of Ikaros ans p53 increased, compared with those of Kras. The reason may be that simultaneous exposure could increase the mutation frequency of Ikaros and p53 by generating a wide variety of mutation, whereas the Kras gene has limited target site of mutagenesis. The results suggest Ikaros and p53 mutation contributed more to lymphomagenesis by simultaneous exposure than Kras, and simultaneous exposure provides new generated and complex carcinogenic mechanism., 2nd Asian Congress of Radiation Research (ACRR2009)},
 title = {Comparison of Ikaros, p53 and Kras point mutation in mouse thymic lymphomas induced by simultaneous exposure to X-ray and N-ethyl-N-nitrosourea.},
 year = {2009}
}