Biological significance of trace levels of mutagenic heterocyclic aromatic amines in human diet: a critical review.
Cooking of protein-rich foods may induce the formation of a series of heterocyclic aromatic amines (HAAs) that have been found to be mutagens and carcinogens. Despite very potent mutagenic activity found in the Salmonella/microsomal assay, this test cannot predict carcinogenic potency of HAAs in rodents and monkeys. Doses used in the feeding studies with animals exceeded by several orders of magnitude the levels of HAAs found in human diet, being approximately 500,000-3,000,000-fold higher than the human dietary levels. A comparison of these levels and their relevance for humans is presented. Differences in metabolic fate of different HAAs due to species and sex of the animals are discussed. These differences could account for the variable cancer-producing potential in different species. A number of still unresolved variables (such as the levels of HAAs in foods, bioavailability, possible synergistic effect from mixtures of HAAs, and metabolic fate and detoxification) preclude reliable assessment of the potential health hazard from HAAs in foods. The difference in the ability of human and animal liver microsomes to bioactivate HAAs and to form DNA adducts causes further uncertainty. The differences due to the hepatic cytochrome P-450-mediated activation of HAA among rats, monkeys and humans may influence susceptibility to cancer from these agents. HAAs occur only in traces in the human diet; however, they are present in many foods consumed daily. The levels of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP) are approximately 100-fold higher than the levels of 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). However, their mutagenic potential in the Ames Salmonella assay is reversed. Other in vitro tests, however, indicate similar genotoxicity between IQ, MeIQx and PhIP. Although most feeding studies with HAAs have been conducted with IQ and MeIQ, evidence obtained from a variety of studies indicates the possibility that PhIP may have an active role in the aetiology of human cancer and, therefore, its role as such should be evaluated. The influence of trace levels of HAAs on human health remains to be confirmed.
Stavric
B
B
Food Research Division, Health Protection Branch, Health and Welfare Canada, Ottawa, Ontario.
D000588:Amines / Q000032:analysis / Q000633:toxicity*; D000818:Animals; D001682:Biological Availability; D002273:Carcinogens / Q000032:analysis / Q000633:toxicity*; D004032:Diet; D005260:Female; D005504:Food Analysis; D006571:Heterocyclic Compounds / Q000032:analysis / Q000633:toxicity*; D006801:Humans; D008099:Liver / Q000187:drug effects; D008297:Male; D009153:Mutagens / Q000032:analysis / Q000633:toxicity*; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D009369:Neoplasms / Q000139:chemically induced; D012307:Risk Factors; D012727:Sex Characteristics; D013045:Species Specificity
D000588:Amines; D002273:Carcinogens; D006571:Heterocyclic Compounds; D009153:Mutagens