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Ikaros is a critical target during simultaneous exposure to X-rays and N-ethyl-N-nitrosourea in mouse T-cell lymphomagenesis
https://repo.qst.go.jp/records/46478
https://repo.qst.go.jp/records/464787ee9ed1e-0490-46dd-927d-a7dc5f7de15c
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2013-01-09 | |||||
| タイトル | ||||||
| タイトル | Ikaros is a critical target during simultaneous exposure to X-rays and N-ethyl-N-nitrosourea in mouse T-cell lymphomagenesis | |||||
| 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_6501 | |||||
| 資源タイプ | journal article | |||||
| 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× Nishimura, Mayumi× Imaoka, Tatsuhiko× Fujimoto, Shinji× Hino, Okio× Shimada, Yoshiya× 坂入 しのぶ× 柿沼 志津子× 甘崎 佳子× 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 | Cancer risk from radiation in humans is considered to result from simultaneous exposure to natural and manmade carcinogens. Available data are insufficient on the molecular characteristics of cancer after simultaneous exposure to radiation and chemicals. In this study, we used a mouse thymic lymphoma (TL) model that was synergistically induced by simultaneous exposure to X-rays and N-ethyl-N-nitrosourea (ENU) at sub-carcinogenic doses and analyzed the mutation frequency and spectrum of the TL-associated genes Ikaros, Notch1, p53, and Kras. We found that the point mutation frequency in Ikaros was significantly increased to 47% for simultaneous exposure, as compared with 13% and 0% for X-ray and ENU exposure alone, respectively. These mutations were mostly G:C > A:T at non-CpG sites and T:A > C:G, both of which are characteristic of ENU mutagenesis. About half of the point mutations were accompanied by loss of heterozygosity (LOH), typical of X-irradiation. The remaining half did not include LOH, which suggests they were dominant-negative mutations. In Notch1, the abnormality frequency was high (>58%) regardless of the treatment, suggesting that Notch1 aberration may be important for T-cell lymphomagenesis. The p53 and Kras mutation frequencies were low for all treatments (<23%). Importantly, the frequency of TLs containing mutations in multiple genes, especially both Ikaros and Notch1, increased after simultaneous exposure. Thus, after simultaneous exposure, Ikaros is a critical target and is inactivated by ENU–induced point mutations and/or X-ray–induced LOH in T-cell lymphomagenesis. Furthermore, concomitant alterations of multiple tumor-associated genes may contribute to enhanced lymphomagenesis after simultaneous exposure. | |||||
| 書誌情報 |
International Journal of Cancer 巻 132, 号 2, p. 259-268, 発行日 2013-01 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0020-7136 | |||||
