The Japan Radiation Research Society Annual Meeting Abstracts
The 47th Annual Meeting of The Japan Radiation Research Society
Session ID : 3M-01
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Oncogenesis
Dose-response Relation Ship of Radiation-induced Thymic Lymphomas in Scid Mice
*Hiroko Ishii-ohbaShigeru KobayashiMayumi NishimuraYoshiya ShimadaToshiaki OgiuHideo Tsuji
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Abstract
Scid mice have the spontaneous mutation on DNA-PKcs, exhibit the limited activities of DNA double strand break repair and are sensitive to ionizing radiation. Dose-response study of radiation induced thymic lymphoma by 0.05 to 3 Gy irradiation was done, and the quadratic equation was best fitted. The presence of the threshold was not statistically confirmed. In order to study the relationship between the defect of repair capacity for DNA double strand breaks and carcinogenesis in other target cells than thymocytes, the histochemical analysis was done using 1-3 Gy irradiated scid homozygotes, scid heterozygotes and C.B-17 mice. From the Kaplan-Meier analysis, significant difference in tumor free survaival between scid and wild type mice were observed in thymic lymphoma, but not in ovarian granulosa cell tumor, hepatocellular carcinoma, and lung adonocarcinoma. All of which were induced both in scid and wild type mice by 1 Gy gamma-irradiation. Dose-response of Notch1 abnormality in entire region of the gene was linear in scid mice. There are at least two pathways for induction of Notch1 deletions: illegitimate V(D)J recombination and microhomology-mediated NHEJ pathway. Microhomology-mediated NHEJ pathway and insertion of intracisternal A particle are likelly to be responsible for linear induction of Notch1 abnormalities, thereby contributing to thymic lymphoma induction.
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© 2004 The Japan Radiation Research Society
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