Human exposure to heterocyclic amine food mutagens/carcinogens: Relevance to breast cancer

Abstract

Heterocyclic amines produced from overcooked foods are extremely mutagenic in numerous in vitro and in vivo test systems. One of these mutagens, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP), induces breast tumors in rats and has been implicated in dietary epidemiology studies as raising the risk of breast cancer in humans. Efforts in our laboratory and others have centered on defining the exposure to PhIP and other dietary mutagens derived from cooked food. We accomplish this by analyzing the foods with a series of solid-phase extractions and HPLC. We have developed an LC/MS/MS method to analyze the four major human PhIP metabolites (sulfates and glucuronides) following a single meal containing 27 g of cooking-produced PhIP in 200 g of grilled meat. Although the intake of PhIP was similar for each of eight women, the total amount excreted in the urine and the metabolite profiles differed among the subjects. It appears that adsorption (digestion) from the meat matrix, other foods in the diet, and genetic differences in metabolism may contribute to the variation. The four major metabolites that can be routinely assayed in the urine are N 2 -OH-PhIP-N 2 -glucuronide, PhIP-N 2 -glucuronide, 4Ј-PhIP-glucuronide, and N 2 -OH-PhIP-N3-glucuronide. This work is suited to investigate individual exposure and risk, especially for breast cancer, from these potent dietary mutagens.

Dietary Fat and Physical Activity in Relation to Breast Cancer among Polish Women

“…The compounds were found to be extremely mutagenic agents in numerous in vitro and in vivo systems; they are able to increase breast cancer risk (Zheng et al, 1998;Felton et al, 2002). Knize and co-workers (1985; observed that concentration of these carcinogens depends on cooking method, time, temperature and protein source.…”

Base-Displaced Intercalated Structure of the Food Mutagen 2-Amino-3-methylimidazo[4,5-f]quinoline in the Recognition Sequence of the NarI Restriction Enzyme, a Hotspot for −2 bp Deletions

“…5,6 Daily human intakes of HCAs, estimated to be ∼60 ng/day, 7 are modest; however, exposure to these compounds, which have been isolated from human urine, 8 is of concern with regard to human health.…”

Molecular Epidemiology of Cancer

“…Several studies have shown that colorectal cancer cases are more likely to be rapid acetylators if they consume diets high in red meat intake. 10 In some, but not all, studies that assessed exposure to heterocyclic amines by using information on meat intake, and preferred methods of cooking the meat (eg, grilling versus broiling versus roasting), 49 rapid acetylators consuming higher predicted heterocyclic amine intake have again been at somewhat higher risk of colorectal cancer. Studies such as these can help identify the specific human carcinogens in complex mixtures, like diet, and may ultimately lead to preventive advice for populations (eg, changes in meat cooking practices) or individuals (eg, those with susceptibility genotypes for common environmental exposures).…”