Extrapolation of heterocyclic amine carcinogenesis data from rodents and nonhuman primates to humans.
Twenty different heterocyclic amines have been isolated and identified from cooked foods especially beef, fish, pork and fowl. Other HCAs have also been isolated but their structure remains to be elucidated and new HCAs are likely to be identified in the future. The HCAs are highly mutagenic and all ten HCAs that have been tested for carcinogenic activity, produce tumors in mice and rats. For humans the average daily intake of HCAs is in quantities of 10-20 mg/person/day. The HCAs are procarcinogens and are activated by the cytochrome P450 system especially CYP 1A2. Rodents, monkeys and humans have the capacity to activate HCAs. Studies using hepatic microsomes demonstrated that humans have a greater capacity to activate the majority of HCAs tested than rodents or cynomolgus monkeys. Three HCAs are currently under evaluation in nonhuman primates for carcinogenic activity and one, IQ, is highly carcinogenic inducing primary hepatocellular carcinomas in the majority of cynomolgus monkeys treated. Epidemiological studies, although not definitive, are supportive of an association of HCAs intake to the etiology of human cancer. Risk assessments from animal data show a risk of HCAs to humans in the range of 10(-3) to 10(-4) which is an order of magnitude greater than compounds currently regulated by the U.S. Food and Drug Administration or the Environmental Protection Agency. Taken together evidence from mutagenicity data, activation by various species including humans, carcinogenicity in animals, human consumption data, epidemiological studies and risk assessment, supports the conclusion that HCAs are probable human carcinogens.
Adamson
R H
RH
National Cancer Institute, Bethesda, MD 20892, USA.
Thorgeirsson
U P
UP
Sugimura
T
T
D000588:Amines / Q000009:adverse effects / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000009:adverse effects / Q000378:metabolism / Q000633:toxicity*; D004032:Diet; D005511:Food Handling; D006571:Heterocyclic Compounds / Q000009:adverse effects / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000378:metabolism / Q000633:toxicity; D008460:Meat / Q000009:adverse effects; D051379:Mice; D009153:Mutagens / Q000009:adverse effects / Q000378:metabolism / Q000633:toxicity*; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology; D011323:Primates; D011810:Quinoxalines / Q000009:adverse effects / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D018570:Risk Assessment; D013045:Species Specificity; D013329:Structure-Activity Relationship
D000588:Amines; D002273:Carcinogens; D006571:Heterocyclic Compounds; D007093:Imidazoles; D009153:Mutagens; D011810:Quinoxalines; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; C042052:2-amino-3,7,8-trimethylimidazo(4,5-f)quinoxaline