Impact of environmental exposures on the mutagenicity/carcinogenicity of heterocyclic amines.
Carcinogenic heterocyclic amines are produced from overcooked foods and are highly mutagenic in most short-term test systems. One of the most abundant of these amines, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), induces breast, colon and prostate tumors in rats. Human dietary epidemiology studies suggest a strong correlation between either meat consumption or well-done muscle meat consumption and cancers of the colon, breast, stomach, lung and esophagus. For over 20 years our laboratory has helped define the human exposure to these dietary carcinogens. In this report we describe how various environmental exposures may modulate the risk from exposure to heterocyclic amines, especially PhIP. To assess the impact of foods on PhIP metabolism in humans, we developed an LC/MS/MS method to analyze the four major PhIP urinary metabolites following the consumption of a single portion of grilled chicken. Adding broccoli to the volunteers' diet altered the kinetics of PhIP metabolism. At the cellular level we have found that PhIP itself stimulates a significant estrogenic response in MCF-7 cells, but even more interestingly, co-incubation of the cells with herbal teas appear to enhance the response. Numerous environmental chemicals found in food or the atmosphere can impact the exposure, metabolism, and cell proliferation response of heterocyclic amines.
Felton
James S
JS
Biology and Biotechnology Research Program, L-452, Lawrence Livermore National Laboratory, Livermore, CA 94551, USA. feltonl@llnl.gov
Knize
Mark G
MG
Bennett
L Michelle
LM
Malfatti
Michael A
MA
Colvin
Michael E
ME
Kulp
Kristen S
KS
D000818:Animals; D001937:Brassica; D002273:Carcinogens / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism; D002417:Cattle; D002645:Chickens; D003296:Cooking; D004781:Environmental Exposure; D006571:Heterocyclic Compounds / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism; D008460:Meat; D008862:Microsomes, Liver / Q000378:metabolism*; D013662:Tea
D002273:Carcinogens; D006571:Heterocyclic Compounds; D007093:Imidazoles; D013662:Tea; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine