Defective Removal of DMA Cross-Links in a Repair-deficient Mutant of Chinese Hamster Cells1

To further understand the relationships between DNA dam age, DNA repair, and cellular end points such as survival and mutation, the repair capacity of a DNA repair-deficient mutant (strain UV-20) of Chinese hamster ovary cells was character ized in response to DNA cross-linking agents. This mutant, previously shown to be hypersensitive to killing by both ultra violet light and the cross-linking agent mitomycin C, was also found to be extremely sensitive to c/s-diamminedichloroplatinum, another DNA cross-linking agent. The efficiency of DNA cross-link removal after treatment with mitomycin C or c/sdiamminedichloroplatinum was measured using the technique of alkaline elution and compared in wild-type Chinese hamster ovary cells and strain UV-20. Wild-type cells removed 80 or 95% of the cross-links within 24 hr after treatment with cisdiamminedichloroplatinum or mitomycin C, respectively. In contrast, UV-20 cells, which were equally as susceptible to cross-link damage as were wild-type cells, removed only a small proportion of the cross-links made by either agent. These results emphasize the importance of DNA repair processes in modulating the cytotoxic effects of chemicals that produce DNA cross-link damage and suggest that cross-link repair in Chinese hamster ovary cells is controlled by a pathway that also repairs damage from ultraviolet radiation.