Activation of the food-derived mutagen 2-amino-3-methylimidazo[4, 5-f]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]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 micrograms IQ per mg microsomal protein varied from 11, 830 +/- 320 to 42, 830 +/- 290 (mean +/- SD). With the same livers and a dose of 10 micrograms AF per plate the number of revertants varied from 15,770 +/- 1600 to 29,380 +/- 810 per mg microsomal protein. Metyrapone and alpha-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.
McManus
M E
ME
Department of Clinical Pharmacology, School of Medicine, Flinders University of South Australia, Bedford Park.
Burgess
W
W
Stupans
I
I
Trainor
K J
KJ
Fenech
M
M
Robson
R A
RA
Morley
A A
AA
Snyderwine
E G
EG
D001571:Benzoflavones / Q000494:pharmacology; D001711:Biotransformation / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005449:Fluorenes / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008797:Metyrapone / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism*; D011804:Quinolines / Q000378:metabolism* / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000187:drug effects
D001571:Benzoflavones; D005449:Fluorenes; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C012177:2-aminofluorene; C011512:alpha-naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D008797:Metyrapone