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Combined Effects of X-rays and N-Ethyl-N-Nitrosourea on Thymic Lymphoma Induction
https://repo.qst.go.jp/records/62468
https://repo.qst.go.jp/records/6246822db072f-c3cc-459d-869c-e3609c8ebc0a
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2008-03-20 | |||||
| タイトル | ||||||
| タイトル | Combined Effects of X-rays and N-Ethyl-N-Nitrosourea on Thymic Lymphoma Induction | |||||
| 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 |
Kakinuma, Shizuko
× Kakinuma, Shizuko× Yamauchi, Kazumi× Amasaki, Yoshiko× Nishimura, Mayumi× Nakata, Akifumi× Kawaguchi, Isao× Takabatake, Takashi× Imaoka, Tatsuhiko× Shimada, Yoshiya× 柿沼 志津子× 山内 一己× 甘崎 佳子× 西村 まゆみ× 中田 章史× 川口 勇生× 高畠 貴志× 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 | Since we are living in the environment with numerous natural and man-made radiation and chemicals, cancer development in human is considered as a result of interaction with these factors. While high dose of ionizing radiation is well known to contribute to tumor induction, carcinogenic effect of low dose (< 0.2 Gy) is still controversial. To understand the effect of low dose radiation on carcinogenesis, we examined mode and mechanism of combined effect of low dose radiation and chemical carcinogen comparing to those of high dose. For induction of thymic lymphoma (TL), which is a good animal model for human T-cell acute lymphoblastic leukemia, female B6C3F1 mice at 4-weeks of age were exposed weekly to whole body X-irradiation at 0.2 to 1.0 Gy for consecutive 4 weeks, and then given N-ethyl-N-nitrosourea (ENU) in drinking water at 50 to 200 ppm for 4 weeks. Dose-response curve for induction of TL by fractionated X-irradiation or ENU administration had threshold dose, therefore the dose range including threshold dose were used for the combined exposure. The mode of combined effect of high dose X-rays followed by ENU was synergistic, and that of low or threshold dose of X-rays was unexpectedly antagonistic. We previously reported that X-ray-induced TL was characteristic of a high frequency of loss of heterozygosity (LOH) in the centromeric region of chromosome 11, in which we mapped Ikaros, a master gene of lymphopoiesis, but not in ENU-induced or spontaneously developing TL1. In the X-ray-induced TL, a variety of Ikaros alteration including transcriptional silencing, unusual splicing, point mutation and small insertion, most of which were associated with LOH, were observed2. On the other hand, in ENU-induced TLs Ikaros was altered by only point mutations without LOH3. Thus, the mutation of Ikaros was distinguished between X-ray- and ENU-induced TL. In TL after combined treatment, Ikaros alteration was mainly point mutation without LOH. The analysis of mutation in thymus of B6C3F1 gpt-delta mice demonstrated that combined exposure of 0.2 Gy X-rays with ENU dramatically decreased mutant frequency, especially G:C to A:T and A:T to T:A mutations, compared to ENU treatment alone4. In contrast, 1.0 Gy X-rays combined with ENU enhanced mutant frequency, indicating a good correlation with carcinogenic response. In conclusion, the mode of combined effect of X-rays and ENU on TL induction and mutant frequency was dependent upon the dose of X-rays. | |||||
| 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 | NIRS International Symposium on the Effects of Low Dose Radiation | |||||
| 発表年月日 | ||||||
| 日付 | 2008-02-14 | |||||
| 日付タイプ | Issued | |||||
