Some perspectives on the nutritional aspects of breast cancer research. Food-derived heterocyclic amines as etiologic agents in human mammary cancer.

Epidemiologic and experimental evidence indicates that dietary factors influence the incidence of mammary gland cancer. The dietary causes of this cancer, however, remain largely unknown. This paper reviews the experimental studies implicating the food-derived heterocyclic amines (HAs) in human breast cancer. Heterocyclic amines are formed at the parts-per-billion levels in meats, such as beef, chicken, pork, and fish, cooked by ordinary methods. 2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) is among the most prevalent of the HAs in fried and barbecued beef, a staple of the American diet. Chronic administration of PhIP in the diet has been shown to cause mammary gland cancer in rats. Two other food-derived HAs, 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, also have been shown to be mammary carcinogens in rodent models. In rats, heterocyclic amines produce DNA adducts in the mammary gland after metabolic activation. Studies examining human urine for HAs and metabolites confirm that humans who consume cooked meats are exposed to HAs. Studies also reveal that humans can activate HAs metabolically. Therefore, the experimental evidence suggests that the food-derived HAs may be etiologic agents in human breast cancer. Humans, however, are exposed to a complex mixture of carcinogenic and anticarcinogenic agents through their diets. Experimental studies examining the interaction between HAs and other dietary factors with respect to mammary carcinogenesis are warranted.