TY - JOUR
T1 - Activation of the food-derived mutagen 2-amino-3-methylimidazo[4,5-ƒ]quinoline by human-liver microsomes
AU - McManus, Michael E.
AU - Burgess, Wendy
AU - Stupans, Ieva
AU - Trainor, Kevin J.
AU - Fenech, Michael
AU - Robson, Richard A.
AU - Morley, Alexander A.
AU - Snyderwine, Elizabeth G.
PY - 1988/2
Y1 - 1988/2
N2 - 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.
AB - 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.
KW - 2-Amino-3-methylimidazo[4,5-f{hook}]quinoline (IQ)
KW - Cytochrome P450
KW - Human-liver microsomes
KW - Lymphocytes
UR - http://www.scopus.com/inward/record.url?scp=0023865003&partnerID=8YFLogxK
U2 - 10.1016/0165-1218(88)90088-2
DO - 10.1016/0165-1218(88)90088-2
M3 - Article
C2 - 3278209
AN - SCOPUS:0023865003
SN - 0165-1218
VL - 204
SP - 185
EP - 193
JO - Mutation Research/Genetic Toxicology
JF - Mutation Research/Genetic Toxicology
IS - 2
ER -