Mutagenic response and repair of cis-DDP-induced DNA cross-links in the Chinese hamster V79 cell mutant V-H4 which is homologous to Fanconi anemia (group A)

Abstract

Previously, it has been shown that the V-H4 mutant of Chinese hamster V79 cells is homologous to Fanconi anemia (FA) group A cells. This hamster cell mutant shows a specific sensitivity to DNA cross-linking agents; therefore, the induction and repair of DNA cross-links were studied in V-H4 and wild-type V79 cells after cis-DDP treatment by the DNA alkaline elution technique. A significant difference in repair of these lesions in V-H4 and wild-type cells was observed. After the cis-DDP treatment (24 h) about 3 times more cross-links remained in V-H4 cells in comparison to the parental V79 cells. These results indicate that the process of cross-link repair in V-H4 cells is hamperedwhen compared to that of wild-type cells. To assess the effect of slower removal of DNA cross-links on the mutability of V-H4, the induction of mutants at the hypoxanthine-guanine phosphoribosyltransferase locus (HPRT) by cis-DDP was studied in V-H4 and V79 cells. Despite the increased cytotoxicity of cis-DDP to V-H4 cells, the mutation induction at the HPRT locus was not significantly different in both cell lines, but when the frequency of the hprt mutants was plotted against survival, hypomutability was observed in V-H4 cells after the cis-DDP treatment.