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 heterocyclic amines 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP) was examined in the supF gene of PSP189 by a polymerase-arrest assay using thermal-cycle sequencing. The reactive N-acetoxy metabolites of both compounds showed an overwhelming preference for reacting with guanine residues in the supF gene of the shuttle vector pSP189. The distribution of the IQ and PhlP guanine adducts was not random; instead, patterns of adduct hot-spots and cold-spots were observed. There was a striking similarity between both compounds in their preferred sites of adduct formation. The finding 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 predictive of the known sites of mutation hot-spots. In addition, despite the similarity in adduct hot-spots for IQ and PhlP, their reported mutation spectra in the supF gene were different. Factors in addition to adduct location therefore appear to play a role in the mutation spectra induced by the heterocyclic amines in the supF gene. (C) 1995 Wiley-Liss, Inc.