SPECIFICITY OF BASE SUBSTITUTION MUTATIONS INDUCED BY THE DIETARY CARCINOGENS 5-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE (PHLP) AND 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE (IQ) IN SALMONELLA

The base pair substitution mutational profiles induced by the heterocy clic amine cooked Food mutagens PhlP and IQ in Salmonella typhimurium strains TA100 and TA1535 were determined by colony hybridizaiion analy sis. Both PhlP and IQ induced predominantly GC-->TA transversions in s train TA100 (rfa,Delta uvrB/pKM101) with a pronounced preference for t he second codon position (CCC-->CAC; 72% of total). PhlP also reverted strain TA1535 (rfa, Delta uvrB) efficiently at concentrations similar to those required for strain TA100. In contrast to the PhlP-induced m utational profile observed in strain TA100, in strain TA1535 PhlP indu ced exclusively GC-->AT transitions at the second codon position (CCC- ->CTC; 96-99% of total). Base substitution mutagenesis induced by hete rocyclic amines related to PhlP is generally SOS-dependent, requiring the presence of plasmid pKM101 in Salmonella hisG46 strains. Thus, the SOS dependent reversion of S. typhimurium strain TA100 probably refle cts error-prone lesion bypass at the major PhlP-guanosine adduct at th e C-8 position. The GC-->AT transition mutations induced by PhlP in st rain TA1535 appear to be SOS-independent, however, suggesiing that the se mutations may arise from the formation of PhlP-DNA adducts other th an the replication-blocking C8-dG lesion. (C) 1998 Wiley-Liss, Inc.