Activation of the food-derived mutagen 2-amino-3-methylimidazo[4,5-ƒ]quinoline by human-liver microsomes

Michael E. McManus, Wendy Burgess, Ieva Stupans, Kevin J. Trainor, Michael Fenech, Richard A. Robson, Alexander A. Morley, Elizabeth G. Snyderwine

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    11 Citations (Scopus)

    Abstract

    The ability of human-liver microsomes to metabolically activate the food-derived heterocyclic amine, 2-amino-3-methylimidazo[4,5-f{hook}]quinoline (IQ), and the model mutagen, 2-aminofluorene (AF), has been investigated using Salmonella typhimurium TA98. In 6 subjects tested the number of revertants produced by 0.1 μg IQ per mg microsomal protein varied from 11, 830 ± 320 to 42, 830 ± 290 (x ± SD). With the same livers and a dose of 10 μg AF per plate the number of revertants varied from 15770 ± 1600 to 29380 ± 810 per mg microsomal protein. Metyrapone and α-naphthoflavone caused differential inhibition of the mutagenesis of both IQ and AF indicating the involvement of different forms of cytochrome P450 in the metabolic activation of these amines in human-liver microsomes. In presence of human-liver microsomes IQ produced no detectable increase in mutations at the hypoxanthine phosphoribosyl transferase locus in lymphocytes and caused no increase in micronuclei formation at realistic exposure levels.

    Original languageEnglish
    Pages (from-to)185-193
    Number of pages9
    JournalMutation Research/Genetic Toxicology
    Volume204
    Issue number2
    DOIs
    Publication statusPublished - Feb 1988

    Keywords

    • 2-Amino-3-methylimidazo[4,5-f{hook}]quinoline (IQ)
    • Cytochrome P450
    • Human-liver microsomes
    • Lymphocytes

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