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. 1993 Mar;99:123–128. doi: 10.1289/ehp.9399123

Metabolism of the food-borne carcinogens 2-amino-3-methylimidazo-[4,5-f]quinoline and 2-amino-3,8- dimethylimidazo[4,5-f]-quinoxaline in the rat as a model for human biomonitoring.

R J Turesky 1, W G Stillwell 1, P L Skipper 1, S R Tannenbaum 1
PMCID: PMC1567061  PMID: 8319609

Abstract

Metabolism of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,8-dimethylimidazol[4,5-f]quinoxaline (MeIQx) and their binding to blood proteins were examined in the rat to develop methods of human biomonitoring. Hemoglobin and serum albumin were among many blood proteins modified. Approximately 0.01% of the dose for both compounds was bound to these proteins, and induction of cytochrome P-450 with polychlorobiphenyls resulted in decreased levels of adduction. Hemoglobin sulfinic acid amide adducts could not be detected for either amine, however, as much as 10% of the IQ bound to albumin was characterized as an N2-cysteine(34)sulfinyl-IQ linkage. Human dosimetry of these carcinogens through such adducts may prove difficult due to the low levels of protein binding. Major routes of detoxification of both contaminants included cytochrome P-450-mediated ring hydroxylation at the C-5 position followed by conjugation to glucuronic or sulfuric acid. Direct conjugation to the exocyclic amine group through N-glucoronidation and sulfamate formation were other important routes of inactivation, but N-acetylation was a minor pathway. The N-glucoronide conjugate of the mutagenic metabolite N-hydroxy-MeIQx was also detected in urine. Rats given MeIQx at 10 micrograms/kg excreted 20% of the dose in urine within 24 hr and the remainder was recovered in feces. The N2-glucuronide was the major metabolite found in urine and accounted for 4% of the total dose. The other metabolites cited above also were excreted in urine at amounts ranging from 0.5 to 3% of the dose, whereas 0.5 to 2% was detected as unmetabolized MeIQx.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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