Dietary modulation of the carcinogenicity of the heterocyclic amines.
Heterocyclic amines (HCAs) are potent mutagens and carcinogens formed during cooking of meats or fish. They are, therefore, widely consumed by humans.


OBJECTIVE
A series of studies explore modulation of the mutagenicity and carcinogenicity of typical HCAs like 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and of 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP), through dietary fat, green or black tea, and tea polyphenols like epigallocatechin gallate (EGCG) and theaflavin gallate (TFG). Also examined was the carcinogenicity of the bacterial metabolite of IQ, 7-oxo-IQ.


METHODS
Male and female F344 rats were fed diets with 75 ppm IQ for 12 months, and containing 5% or 20% corn oil. Complete necropsies after 15 months (males), or 18 months (females) were performed. Modification of the action of IQ and of PhIP in tests for bacterial mutagenicity (Ames test) or DNA repair in male rat hepatocytes (Williams test) by teas, EGCG or TFG was studied. Also compared was the activity of IQ and of 7-oxo-IQ in the tests of Ames and of Williams, and their carcinogenicity in male F344 rats upon intrarectal infusion.


RESULTS
A high fat diet increased the carcinogenicity of low levels of IQ at several target organs. Multiple benign and malignant sebaceous skin tumors were noted in males but not in females. Green or black teas, EGCG, and TFG sharply reduced the mutagenicity of IQ and PhIP, and especially lowered the activity of IQ and of PhIP in the Williams test. 7-Oxo-IQ was active only in the Ames test, but not in the Williams test. Also, it was not carcinogenic, confirming that chemicals positive in the Ames test but negative in the Williams test are not likely carcinogens.


CONCLUSIONS
The in vitro and in vivo effects of HCAs can be modified by dietary components such as fats or teas. An understanding of the underlying mechanisms may provide practical and realistic means of risk assessment, and may lower the risk associated with these nutritional carcinogens widespread in the human environment.
Weisburger
J H
JH
American Health Foundation Valhalla, New York 10595, USA.
Rivenson
A
A
Kingston
D G
DG
Wilkins
T D
TD
Van Tassell
R L
RL
Nagao
M
M
Sugimura
T
T
Hara
Y
Y
D000588:Amines / Q000633:toxicity*; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology; D002273:Carcinogens / Q000633:toxicity*; D003110:Colonic Neoplasms / Q000139:chemically induced; D004260:DNA Repair / Q000187:drug effects*; D004032:Diet; D004041:Dietary Fats; D005260:Female; D006571:Heterocyclic Compounds / Q000633:toxicity*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D008826:Microbial Sensitivity Tests; D009153:Mutagens / Q000633:toxicity; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D018570:Risk Assessment; D012727:Sex Characteristics; D012878:Skin Neoplasms / Q000139:chemically induced; D013662:Tea
D000588:Amines; D016587:Antimutagenic Agents; D002273:Carcinogens; D004041:Dietary Fats; D006571:Heterocyclic Compounds; D009153:Mutagens; D013662:Tea