THE EFFECT OF DEFECTIVE-DNA DOUBLE-STRAND BREAK REPAIR ON MUTATIONS AND CHROMOSOME-ABERRATIONS IN THE CHINESE-HAMSTER CELL MUTANT XR-V15B

The radiosensitive Chinese hamster cell line XR-V15B was used to study the effect of decreased rejoining of DNA double-strand breaks (DSBs) on gene mutations and chromosome aberrations. XR-V15B cells are hypers ensitive to the cytotoxic effects of neocarzinostatin (NCS) and methyl methanesulfonate (MMS). Both mutagens induced more chromosome aberrat ions in XR-V15B cells than in the parental cell strain. The clastogeni c action of NCS was characterized by the induction of predominantly ch romosome-type aberrations in cells of both strains, whereas MMS induce d mainly chromatid aberrations. The frequency of induced gene mutation s at the hprt locus was not increased compared to the parental V79 cel ls when considering the same survival level. Molecular analysis by mul tiplex polymerase chain reaction (PCR) of mutants induced by NCS revea led a high frequency of deletions in cells of both cell lines. Methyl methanesulfonate induced mainly mutations without visible changes in t he PCR pattern, which probably represent point mutations. Our findings suggest a link between a defect in DNA DSB repair and increased cytot oxic and clastogenic effects. However, a decreased ability to rejoin D NA DSBs does not seem to influence the incidence and types of gene mut ations at the hprt locus induced by NCS and MMS. (C) 1995 by Radiation Research Society