Effect of enzyme inducers on the metabolism of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in the rat.
The effect of enzyme inducers 3-methylcholanthrene (3-MC) and Aroclor 1254 (A-1254) on the metabolic fate of the dietary mutagen and carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in male F344 rats was studied in relation to single dose corn oil and untreated controls. The latter two groups were similar as regards metabolism of IQ. However, the ratio of total metabolites excreted in urine compared with those in feces was higher in A-1254 pretreated rats. In fact, this distinct excretory pattern stemmed from a lower level of IQ-N-sulfamate, and a considerably higher level of 5-OH-IQ sulfate ester, a major metabolite in urine of A-1254-injected rats. Interestingly, 5-OH-IQ glucuronide urinary levels were unaffected by the treatment. Thus, the direct 5-hydroxylation of IQ appears to be considerably increased by 3-MC and more so by A-1254, and under those conditions the resulting 5-OH-IQ is preferentially converted to the sulfate ester, in turn readily excreted in urine.
Vavrek
M T
MT
American Health Foundation, Valhalla, NY 10595-1599.
Sidoti
P
P
Reinhardt
J
J
Weisburger
J H
JH
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D002273:Carcinogens / Q000378:metabolism*; D020111:Chlorodiphenyl (54% Chlorine); D004790:Enzyme Induction; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D009153:Mutagens / Q000378:metabolism*; D011804:Quinolines / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D001140:Aroclors; D002273:Carcinogens; D009153:Mutagens; D011804:Quinolines; D020111:Chlorodiphenyl (54% Chlorine); C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D008748:Methylcholanthrene