| First Author | Ishii-Ohba H | Year | 2007 |
| Journal | Mutat Res | Volume | 619 |
| Issue | 1-2 | Pages | 124-33 |
| PubMed ID | 17397880 | Mgi Jnum | J:120953 |
| Mgi Id | MGI:3708418 | Doi | 10.1016/j.mrfmmm.2007.02.028 |
| Citation | Ishii-Ohba H, et al. (2007) Existence of a threshold-like dose for gamma-ray induction of thymic lymphomas and no susceptibility to radiation-induced solid tumors in SCID mice. Mutat Res 619(1-2):124-33 |
| abstractText | Severe combined immune deficiency (SCID) mice exhibit limited repair of DNA double-strand breaks and are sensitive to ionizing radiation due to a mutation of the DNA-dependent protein kinase catalytic subunit gene. To elucidate the effects of deficient DNA double-strand break repair on radiation-induced carcinogenesis, the dose-response relationship for the induction of all tumor types was examined in wild-type and SCID mice. In wild-type mice, the incidence of thymic lymphomas at gamma-ray doses up to 1Gy was almost equal to the background level, increased gradually above 1Gy, and reached a maximum of 12.5% at 5Gy, which is indicative of a threshold dose of less than 1Gy. SCID mice were extremely susceptible to the induction of spontaneous and radiation-induced thymic lymphomas. The incidence of thymic lymphomas in SCID mice irradiated with 0.1Gy or less was similar to the background level; that is, it increased markedly from 31.7% at 0.1Gy to 51.4% at 0.25Gy, and reached a maximum of 80.6% at 2Gy, suggesting the presence of a threshold-like dose at low gamma-ray doses, even in radiosensitive SCID mice. As the average latency for the induction of thymic lymphomas at 0.1Gy was significantly shortened, the effect of 0.1Gy gamma-rays on thymic lymphoma induction was marginal. The high susceptibility of SCID mice to develop thymic lymphomas indicates that thymic lymphomas are induced by a defect in DNA double-strand break repair or V(D)J recombination. Excessive development of tumors other than thymic and nonthymic lymphomas was not observed in SCID mice. Furthermore, our data suggest that the defective double-strand break repair in SCID mice is not a major determinant for the induction of nonlymphoid tumors. |
