Species differences in metabolism of heterocyclic aromatic amines, human exposure, and biomonitoring

R. J. Turesky, G. A. Gross, W. G. Stillwell, P. L. Skipper, S. R. Tannenbaum

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Abstract

Heterocyclic aromatic amines (HAAs) are animal carcinogens and suspected human carcinogens which are formed in cooked foods at the low parts per billion level. HAAs in cooked meats were purified by either immunoaffinity chromatography or solid phase tandem extraction, which allowed for the simultaneous analysis of 11 HAAs by HPLC. The metabolism of two prominent HAAs, 2-amino-3,8-dimethylimidazo- [4,5-f]quinoxaline (Me/Qx) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), was investigated in animal models and in vitro with human tissues to develop strategies for human biomonitoring. Me/Qx and IQ are rapidly absorbed from the gastrointestinal tract of rodents and transformed into several detoxification products which are excreted in urine and feces. Metabolites result from cytochrome P450-mediated ring oxidation at the C-5 position followed by conjugation to sulfate or p-glucuronic acid. Other major metabolites include the phase 11 conjugates, N2-glucuronide and N2-sulfamate. A metastable N2-glucuronide conjugate of the genotoxic metabolite of N2-hydroxy-MelQx was also detected in urine and bile. The binding of both carcinogens to blood proteins was low and suggests that human biomonitoring through protein adducts may be difficult. These metabolic pathways exist in nonhuman primates and several of these pathways also occur in vitro with human liver. The urinary excretion of Me/Qx in seven human subjects following consumption of cooked beef or fish ranged between 2 and 22 ng in 12 hr when determined by negative ion chemical ionization GC-MS. After acid hydrolysis of urine, the amount of Me/Qx increased 4- to 10-fold in 6 of the 7 subjects. These acid labile metabolites were identified as the N2-sulfamate and N2-glucuronide following column chromatography and HPLC purification. Thus, amine sulfamation and N2-glucuronidation are important routes of detoxification of Me/Qx in rodents, nonhuman primates, and humans.

Original languageEnglish (US)
Pages (from-to)47-51
Number of pages5
JournalEnvironmental health perspectives
Volume102
Issue numberSUPPL. 6
StatePublished - Jan 1 1994

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Keywords

  • Food mutagens
  • Heterocyclic aromatic amines
  • Human biomonitoring
  • Metabolism

Cite this

Turesky, R. J., Gross, G. A., Stillwell, W. G., Skipper, P. L., & Tannenbaum, S. R. (1994). Species differences in metabolism of heterocyclic aromatic amines, human exposure, and biomonitoring. Environmental health perspectives, 102(SUPPL. 6), 47-51.