The molecular nature of mutations induced by adriamycin at the hprt locus of V79 cells

Adriamycin (AM), a widely used chemotherapeutic drug, induced a broad spectrum of gene mutations at the hprt locus of V79 cells. The frequency and distribution of AM-induced deletions was analyzed with multiplex polymerase chain reaction in two V79 cell lines, which differed considerably in their spontaneous deletion frequency. Among AM-induced mutants, deletions predominated in both cell lines. Apart from total deletions of the hprt gene, partial deletions were found which were distributed all over the hprt gene with breakpoints in nearly all introns. Under the same experimental conditions, chromosome aberrations were induced by AM which mainly represented chromatid-type aberrations. Neither the induction of gene mutations nor the induction of chromosome aberrations was enhanced by the repair inhibitor 3-aminobenzamide. These results are discussed in the context with our earlier findings on bleomycin-induced mutations and it is suggested that at least two mechanisms lead to the formation of gene deletions. One of them seems to be associated with a misrepair process of frank DNA double-strand breaks and related to chromosome aberrations while the other is not.