@misc{oai:repo.qst.go.jp:00070671,
 author = {Hirano, Shinobu and 坂入 しのぶ},
 month = {Dec},
 note = {Background: 
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.
\nMaterials and  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.
\nResults and Discussion:
The simultaneous exposure to X-rays and ENU increased thymic lymphoma incidence in a synergistic manner at high doses. 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 compared to single 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. 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., KIDS workshop 2009 in NIRS},
 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}
}