Relationship between DNA Repair and Carcinogenesis in Radiosensitive Mutant Mice

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Severe combined immunodeficient (scid) mice are known to be radiosensitive due to their heritable defects of repair of double strand breaks induced by ionizing radiation. We studied the effects of scid mutation on the acute as well as late effects of radiation. Acute 50% lethal dose of gamma-rays for scid, Fl and C.B-17 mice was 4.1,6.5 and 7.1 Gy, respectively. When mice were irradiated with same dose, survival period of Fl mice was shorter than that of C.B-17 mice. The bone marrow cells of scid mice were also radiosensitive as compared to those from other 2 strains. Bone marrow cells from Fl mice were slightly but significantly more radiosensitive than that from C.B-17 mice. These results mean that scid hetrozygotes are more resistant to ionizing radiation when compared with scid homozygotes, but more sensitive than wild-type. In late effect studies, groups of scid, Fl and C.B-17 mice were exposed to a single whole body dose of 1-3 Gy of gamma-rays. Results clearly indicated that scid mice were extremely susceptible for induction of thymic lymphomas as compared to other 2 strains. No difference for induction of thymic lymphomas was observed between Fl mice and C.B-17 mice. Ethyl-nitrosourea, a strong lymphomagen, was administered to scid mice. However, incidence of thymic lymphomas were not so high. These results indicate that close relationship between radiosensitivity and susceptibility for radiogenic development of thymic lymphomas was proved, but effect of scid heterozygosity was not demonstrated. Almost all thymic lymphomas of scid mice were CD4/CD8 double positive. In other organs, relationship between radiosensitivity and susceptibility for tumor development was not demonstrated in this system. Further studies are needed to analyze the effects of scid mutation radiation-induced development of solid tumors.