Study on abnormality of DNA recombination in LEC strain rat

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1. Immortalized cell lines from LEC strain (LEC) rats by SV40 large T antigen were more sensitive to X-irradiation than the cell lines from WKAH strain (WKAH) rats, but not to UV-irradiation.2. DNA synthesis in the cell lines of LEC rats was more resistant to X- and UV-irradiation than that of WKAH rats.3. The radiation-induced delay in the progression from the G1 phase to S phase (G1 arrest) was observed in WKAH cells, but not in LEC cells. The intensities of the p53 protein bands increased following irradiation in WKAH cells, but not in LEC cells.4. LEC rat cells were 2-to 3-fold more sensitive to bleomycin (BLM) that induces DNA double-strand breaks (dsbs), and to cross-linking agent, mitomycin C,than WKAH rat cells, while they were slightly sensitive to alkylating agents, ethyl nitrosourea and N-methyl-N'-nitrosoguanidine. Although no difference was observed in the initial yields of DNA dsbs induced by BLM between LEC and WKAH cells, the repair process of DNA dsbs was significantly slower in LEC cells than WKAH cells.These results showed that the enhanced cellular sensitivity is segregated from the resistant phenotype of DNA synthesis to DNA-damaging agents. The radioresistant DNA synthesis in LEC cells is thought to be due to the deficiency in the transient cell cycle arrest from the G1 to S phases. Furthermore, it is suggested that abnormality in the repair of DNA dsbs might be associated with the abnormality of DNA recombination process. LEC rat could provide a useful animal model to assist in an understanding of the mechanism of the repair process of the radiation-induced DNA damage including DNA recombination and regulation of the cell cycle.