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While high dose of ionizing radiation is well known to contribute to tumor induction, carcinogenic effect of low dose (\u003c 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.  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  1. 学会発表・講演等
  2. 口頭発表

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/62468
22db072f-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

WEKO 617222

Kakinuma, Shizuko

Search repository
Yamauchi, Kazumi

× Yamauchi, Kazumi

WEKO 617223

Yamauchi, Kazumi

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Amasaki, Yoshiko

× Amasaki, Yoshiko

WEKO 617224

Amasaki, Yoshiko

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Nishimura, Mayumi

× Nishimura, Mayumi

WEKO 617225

Nishimura, Mayumi

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Nakata, Akifumi

× Nakata, Akifumi

WEKO 617226

Nakata, Akifumi

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Kawaguchi, Isao

× Kawaguchi, Isao

WEKO 617227

Kawaguchi, Isao

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Takabatake, Takashi

× Takabatake, Takashi

WEKO 617228

Takabatake, Takashi

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Imaoka, Tatsuhiko

× Imaoka, Tatsuhiko

WEKO 617229

Imaoka, Tatsuhiko

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Shimada, Yoshiya

× Shimada, Yoshiya

WEKO 617230

Shimada, Yoshiya

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柿沼 志津子

× 柿沼 志津子

WEKO 617231

en 柿沼 志津子

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山内 一己

× 山内 一己

WEKO 617232

en 山内 一己

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甘崎 佳子

× 甘崎 佳子

WEKO 617233

en 甘崎 佳子

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西村 まゆみ

× 西村 まゆみ

WEKO 617234

en 西村 まゆみ

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中田 章史

× 中田 章史

WEKO 617235

en 中田 章史

Search repository
川口 勇生

× 川口 勇生

WEKO 617236

en 川口 勇生

Search repository
高畠 貴志

× 高畠 貴志

WEKO 617237

en 高畠 貴志

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今岡 達彦

× 今岡 達彦

WEKO 617238

en 今岡 達彦

Search repository
島田 義也

× 島田 義也

WEKO 617239

en 島田 義也

Search repository
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
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