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

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.