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Specificity of base substitution mutations induced by the dietary carcinogens 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in Salmonella
Authors:WH Koch  RW Wu  TA Cebula  JS Felton
Abstract:The base pair substitution mutational profiles induced by the heterocyclic amine cooked food mutagens PhIP and IQ in Salmonella typhimurium strains TA100 and TA1535 were determined by colony hybridization analysis. Both PhIP and IQ induced predominantly G→TA transversions in strain TA100 (rfa,ΔuvrB/pKM101) with a pronounced preference for the second codon position (CC→CAC; 72% of total). PhIP also reverted strain TA1535 (rfa, ΔuvrB) efficiently at concentrations similar to those required for strain TA100. In contrast to the PhIP-induced mutational profile observed in strain TA100, in strain TA1535 PhIP induced exclusively G→AT transitions at the second codon position (CC→CTC; 96–99% of total). Base substitution mutagenesis induced by heterocyclic amines related to PhIP 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 reflects error-prone lesion bypass at the major PhIP- guanosine adduct at the C-8 position. The G→AT transition mutations induced by PhIP in strain TA1535 appear to be SOS-independent, however, suggesting that these mutations may arise from the formation of PhIP-DNA adducts other than the replication-blocking C8-dG lesion. Environ. Mol. Mutagen. 31:327–332, 1998 © 1998 Wiley-Liss, Inc.
Keywords:heterocyclic amines (HAs)  2-amino-1-methy-6-phenylimidazo[b4  5-b]pyridine (PhIP)  2-amino-3-methylimidazo[4  5-f]quinoline (IQ)  cooked food mutagens  carcinogens  Salmonella  base substitutions  mutation specificity
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