DISTRIBUTION OF THE DNA-ADDUCTS OF 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE AND 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE IN THE SUPF GENE AS DETERMINED BY POLYMERASE ARREST ASSAY

The distribution of the adducts of the cooked meat-derived heterocycli c amines 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-me thyl-6-phenylimidazo[4,5-b]pyridine (PhlP) was examined in the supF ge ne of PSP189 by a polymerase-arrest assay using thermal-cycle sequenci ng. The reactive N-acetoxy metabolites of both compounds showed an ove rwhelming preference for reacting with guanine residues in the supF ge ne of the shuttle vector pSP189. The distribution of the IQ and PhlP g uanine adducts was not random; instead, patterns of adduct hot-spots a nd cold-spots were observed. There was a striking similarity between b oth compounds in their preferred sites of adduct formation. The findin g that IQ and PhlP adducted to guanine concurred with previous results showing that the target sites for IQ and PhlP mutations in supF were also at guanine. However, the adduct hot-spot sites were not predictiv e of the known sites of mutation hot-spots. In addition, despite the s imilarity in adduct hot-spots for IQ and PhlP, their reported mutation spectra in the supF gene were different. Factors in addition to adduc t location therefore appear to play a role in the mutation spectra ind uced by the heterocyclic amines in the supF gene. (C) 1995 Wiley-Liss, Inc.