Metabolites of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) in human urine after consumption of charbroiled or fried beef

Heterocyclic amines (HAs) are carcinogenic combustion products formed during the cooking of meat at moderate to high temperatures. PhIP is the most common HA formed in fried, grilled or broiled meat, and is a colon, breast, and prostate carcinogen in rodents. The major metabolites of PhIP detected in human urine are N(2)-OH-PhIP-N(2)-glucuronide, PhIP-N(2)-glucuronide, N(2)-OH-PhIP-N(3)-glucuronide, and 4'-PhIP-sulphate. We have measured the time course of PhIP in untreated and acid- or alkali-hydrolyzed urines from 10 healthy non-smoking subjects ingesting identical amounts of char-broiled beef (containing both HAs and PAHs) for 5 days. The morning after the first day of broiled beef consumption (containing 7.7 micro g PhIP), urinary concentration of PhIP increased 14- to 38-fold above mean prefeed concentration. Following cessation of broiled meat consumption, urinary PhIP declined to near prefeed levels within 48-72 h. The ratio of alkali-labile PhIP metabolites to unmetabolized PhIP varied by 2.7-fold among subjects, ranging from 18:1 to 48:1. In a subsequent study we measured PhIP in acid-hydrolyzed urine from 66 subjects ingesting beef pan-fried at high temperature. A significant correlation (r=0.61, P<0.0001) was observed between the amount of fried meat ingested and concentration of PhIP in urines collected between 0 and 12h after feeding. Other investigators have identified 2-OH-PhIP in acid-hydrolyzed urine from these subjects, and also observed a significant correlation (r=0.52, P