@article{oai:repo.qst.go.jp:00047308,
 author = {Kokubo, Toshiaki and Kakinuma, Shizuko and Kobayashi, Toshiyuki and Watanabe, Fumiko and Iritani, Riichirou and Tateno, Kaori and Nishimura, Mayumi and Nishikawa, Tetsu and Hino, Okio and Shimada, Yoshiya and 小久保 年章 and 柿沼 志津子 and 渡辺 文子 and 舘野 香里 and 西村 まゆみ and 西川 哲 and 樋野 興夫 and 島田 義也},
 issue = {3},
 journal = {Cancer Science},
 month = {Feb},
 note = {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.},
 pages = {616--623},
 title = {Age dependence of radiation-induced renal cell carcinomas in an Eker rat model},
 volume = {101},
 year = {2010}
}