On the nature of the mutations induced by the diolepoxide of benzo[a]pyrene in mammalian cells

We have previously described the induction by r-7,t-8-di-hydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) of 8-azaguanine resistant (ACr) Chinese hamster V79 cell mutants, 40% of which were found to contain material which cross-reacted (CRM) with antiserum to hypoxanthine-guanine phosphoribosyltransferase (HPRT) and whose AGr phenotype we ascribed to missense mutation (Brookes et al., 1982). We now report that we have been unable to demonstrate by Southern blotting any change in the HPRT gene in 11 CRM-negative mutants. We have, moreover, found HPRT mRNA of normal size and amount in most of these mutants. Examination of the revertants of one mutant indicates the probable occurrence of changes within an amino acid codon in the genesis of mutant and revertant. Our results suggest that BPDE functions primarily as a point mutagen.