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Comparison of Ikaros, p53 and Kras point mutation in mouse thymic lymphomas induced by simultaneous exposure to X-ray and N-ethyl-N-nitrosourea.
https://repo.qst.go.jp/records/69756
https://repo.qst.go.jp/records/697568f412a93-341c-49fe-91e0-a8514f2419b8
Item type | 会議発表用資料 / Presentation(1) | |||||
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公開日 | 2009-05-25 | |||||
タイトル | ||||||
タイトル | Comparison of Ikaros, p53 and Kras point mutation in mouse thymic lymphomas induced by simultaneous exposure to X-ray and N-ethyl-N-nitrosourea. | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
資源タイプ | conference object | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Hirano, Shinobu
× Hirano, Shinobu× Kakinuma, Shizuko× Amasaki, Yoshiko× Kowatari, Norie× Yamauchi, Kazumi× Nishimura, Mayumi× Imaoka, Tatsuhiko× Shimada, Yoshiya× 坂入 しのぶ× 柿沼 志津子× 甘崎 佳子× 古渡 礼恵× 山内 一己× 西村 まゆみ× 今岡 達彦× 島田 義也 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 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. |
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会議概要(会議名, 開催地, 会期, 主催者等) | ||||||
内容記述タイプ | Other | |||||
内容記述 | 2nd Asian Congress of Radiation Research (ACRR2009) | |||||
発表年月日 | ||||||
日付 | 2009-05-20 | |||||
日付タイプ | Issued |