MUTAGENICITY OF 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE IN HUMAN LYMPHOBLASTOID-CELLS

2-Amino-3-methylimidazo[4,5-f]quinoline (IQ), a heterocyclic aromatic amine that has been identified in cooked meats and cigarette condensat es, is mutagenic in human lymphoblastoid TK6 cells at the thymidine ki nase and hypoxanthine-guanine phosphoribosyl transferase (hprt) loci. Treatment of the cells with IQ following activation with either an exo genous metabolizing mixture (S9) or following photoactivation of the a zido-derivative of IQ (N-3-IQ) showed that the photolytic-derivative o f N-3-IQ was more active. This observation is consistent with other re ports that indicate that the weak mutagenicity of IQ in mammalian cell s is caused hy the lack of enzymes required for the ultimate activatio n of the compound within the cells, Two DNA adducts were found by P-32 -post-labelling in the cells treated with the photoactivated N-3-IQ, T he major adduct was identified as osin-8-yl)-2-amino-3-methylimidazo[4 ,5-f]quinoline (dG-C8-IQ) and the minor adduct as in-N-2-yl)-2-amino-3 -methylimidazo[4,5-f]quinoline (dG-N-2-IQ). The ratio of the dG-C8-IQ to the dG-N-2-IQ adducts was similar to 3:1 and did not significantly change in cultures treated with different concentrations of the mutage n. Approximately 50% of the adducts were removed 9 h after treatment w ith IQ and <10% of these adducts remained after 24 h, There was no sig nificant preferential repair of either adduct under the experimental c onditions used. The identification of 15 mutations induced at the hprt locus (of the 44 mutants analysed) showed IQ to be efficient at induc ing single base deletions in a run of guanines, Six single guanine del etions were observed in the run of six guanines in exon III and one de letion of a single guanine was observed in a nonrepetitive sequence in exon VI, Other mutations observed were two GC-->TA transversions, two GC-->CG transversions, one AT-->TA transversion and one GC-->AT trans ition. In addition, two multiple mutations were found. The majority of the identified mutations (12/15) occurred at GC base pairs and sugges ts either the dG-C8-IQ or the dG-N-2-IQ adduct to be the pre-mutagenic lesion.