2-Amino-3-methyl-imidazol(4,5-f)quinoline (IQ) is a heterocyclic arylamine found in certain cooked foods such as beef and fish. IQ has been shown to be carcinogenic to both rodents and monkeys and to form DNA adducts in tissues of these animals fed IQ. It is well recognized that metabolism can play an important role in the carcinogenicity of chemicals. Therefore we have been examining the disposition of IQ in monkeys and identifying urinary and fecal metabolites of IQ which may be indicative of pathways of carcinogen activation or detoxification. Following administration of 14C-IQ (2 mumol/kg) to cynomolgus monkeys by nasal-gastric intubation, blood levels declined rapidly from 1 to 8 hr following dosing. This was followed by a slow decline from 8 to 72 hr. Approximately 3045% of the dose was excreted in the urine by 8 hr and by 72 hr 45-60% had been excreted. Through HPLC analysis we have observed that IQ is extensively metabolized in monkeys to at least 4 urinary metabolites. No IQ itself was found in the urine. We have found that one of the metabolites is IQ-N-sulfamate. In addition, we have tentatively identified two glucuronides of IQ by their sensitivity to beta-glucuronidase. Structural identification of these metabolites is currently underway.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Epidemiology And Genetics (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP005496-04
Application #
3896366
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code