doi:10.1111/j.1349-7006.2009.01456.x

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量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。
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Permalink : http://id.nii.ac.jp/1657/00047295/

Age dependence of radiation-induced renal cell carcinomas in an Eker rat model 利用統計を見る

アイテムタイプ	学術雑誌論文 / Journal Article
言語	英語
著者	Kokubo Toshiaki Kakinuma Shizuko Kobayashi Toshiyuki Watanabe Fumiko Iritani Riichirou Tateno Kaori Nishimura Mayumi Nishikawa Tetsu Hino Okio Shimada Yoshiya
抄録	Exposure to carcinogens early in life may contribute to cancer development later in life. The amount of radiation exposure to children during medical procedures has been increasing, so it is important to evaluate the radiation risk of cancer in developing organs. Toward this goal, we assessed the risk of developing renal cell carcinoma using Eker rats as a kidney tumor model. F1 hybrids of male Eker (Tsc2 mutant) and female F344 rats were irradiated with 0.5 or 2 Gy gamma radiation on gestation days 15 and 19, and on postnatal days 5, 20, and 49. At 27 weeks of age, kidneys were examined for proliferative lesions. Preneoplastic lesions such as phenotypically altered tubules increased after postnatal irradiation as a function of age-at-irradiation, and hyperplasia were greatly increased after perinatal and postnatal irradiation. In contrast, development of adenoma and adenocarcinoma were evident in animals irradiated at perinatal ages, being maximal at gestational day 19. The frequency of LOH at the Tsc2 locus was unexpectedly low -0% (0 of 4) for the control, and 17% (6 of 35) for the irradiated group. Irrespective of LOH, the mTOR pathway, which is negatively regulated by the Tsc1/2 complex, was activated in both benign and malignant lesions, as evidenced by phosphorylation of S6 ribosomal protein and 4E-BP1. This suggests that the wild-type Tsc2 allele may be functionally inactivated. In conclusion, the actively growing kidney of (F344 X Eker) F1 rats (Tsc2+/-), at a perinatal age, is at risk for radiation-induced malignant transformation of the renal epithelium associated with mTOR activation.
雑誌名	Cancer Science
巻	101
号	3
ページ	616 - 623
発行年	2010-02
ISSN	1347-9032
DOI	10.1111/j.1349-7006.2009.01456.x
著者版フラグ	none

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