Journal Article

Mutagenicity of 2-amino-3-methylimidazo[4,5-f]quinoline in human lymphoblastoid cells.

P M Leong-Morgenthaler, C Op Het Velt, E Jaccaud and R J Turesky

in Carcinogenesis

Volume 19, issue 10, pages 1749-1754
Published in print October 1998 | ISSN: 0143-3334
Published online October 1998 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/19.10.1749
Mutagenicity of 2-amino-3-methylimidazo[4,5-f]quinoline in human lymphoblastoid cells.

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2-Amino-3-methylimidazo[4,5-f]quinoline (IQ), a heterocyclic aromatic amine that has been identified in cooked meats and cigarette condensates, is mutagenic in human lymphoblastoid TK6 cells at the thymidine kinase and hypoxanthine-guanine phosphoribosyl transferase (hprt) loci. Treatment of the cells with IQ following activation with either an exogenous metabolizing mixture (S9) or following photoactivation of the azido-derivative of IQ (N3-IQ) showed that the photolytic-derivative of N3-IQ was more active. This observation is consistent with other reports that indicate that the weak mutagenicity of IQ in mammalian cells is caused by the lack of enzymes required for the ultimate activation of the compound within the cells. Two DNA adducts were found by 32P-post-labelling in the cells treated with the photoactivated N3-IQ. The major adduct was identified as N-(deoxyguanosin-8-yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-C8-IQ) and the minor adduct as 5-(deoxyguanosin-N2-yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-N2-IQ). The ratio of the dG-C8IQ to the dG-N2-IQ adducts was approximately 3:1 and did not significantly change in cultures treated with different concentrations of the mutagen. Approximately 50% of the adducts were removed 9 h after treatment with IQ and <10% of these adducts remained after 24 h. There was no significant preferential repair of either adduct under the experimental conditions used. The identification of 15 mutations induced at the hprt locus (of the 44 mutants analysed) showed IQ to be efficient at inducing single base deletions in a run of guanines. Six single guanine deletions were observed in the run of six guanines in exon III and one deletion of a single guanine was observed in a non-repetitive sequence in exon VI. Other mutations observed were two GC-->TA transversions, two GC-->CG transversions, one AT-->TA transversion and one GC-->AT transition. In addition, two multiple mutations were found. The majority of the identified mutations (12/15) occurred at GC base pairs and suggests either the dG-C8-IQ or the dG-N2-IQ adduct to be the pre-mutagenic lesion.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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