PAN-FRIED MEAT CONTAINING HIGH-LEVELS OF HETEROCYCLIC AROMATIC-AMINESBUT LOW-LEVELS OF POLYCYCLIC AROMATIC-HYDROCARBONS INDUCES CYTOCHROMEP4501A2 ACTIVITY IN HUMANS

Heterocyclic aromatic amines (HAAs) are formed when meat juices are py rolyzed. In humans HAAs are activated in vivo by cytochrome P4501A2 (C YP1A2) and N-acetyltransferase (NAT2) to mutagens or carcinogens. Whil e activity of NAT2 is noninducible, exposure to cigarettes, polycyclic aromatic hydrocarbons, and cruciferous vegetables has been shown to i nduce CYP1A2 activity in humans. To date, it is unknown if pan-fried m eat, which is consumed at high levels in the United States, is capable of inducing CYP1A2. In order to address this issue, we measured CYP1A 2 and NAT2 activities in 66 healthy nonsmokers (33 males and 33 female s) in a controlled metabolic feeding study. The study was designed to minimize the influence of known inducers of CYP1A2. Subjects consumed meat pan-fried at a low temperature (100 degrees C) for 7 days followe d by 7 days of meat pan-fried at a high temperature (250 degrees C) Th e low temperature-cooked meat had undetectable levels of HAAs while th e high temperature-cooked meat contained high amounts of HAAs [9.0 ng/ g of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2.1 ng/g o f 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), and 32.8 ng/g of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)]. In c ontrast, total polycyclic aromatic hydrocarbon content was similar in both meat samples (10.7 ng/g in low temperature-cooked meat and 10.1 n g/g in high temperature-cooked meat). At the end of each period, subje cts were tested for CYP1A2 and NAT2 enzyme activity by caffeine metabo lism phenotyping. NAT2 activity remained unchanged throughout the stud y while CYP1A2 activity increased in 47 of 65 (72%) of the subjects af ter consuming high temperature-cooked meat (P < 0.0002), suggesting in duction by some compound(s) formed during high temperature cooking. If HAAs are shown to be human carcinogens in epidemiological studies, th en meat cooked at high temperatures may pose an increased cancer risk because it contains both inducers of CYP1A2 and procarcinogens MeIQx, DiMeIQx, and PhIP known to be activated by this enzyme.