title: Concentration of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) in urine and alkali-hydrolyzed urine after consumption of charbroiled beef.
abstract: Heterocyclic amines (HAs) and polycyclic aromatic hydrocarbons are carcinogenic products formed during the cooking of meat at moderate to high temperatures. We have previously shown that the urinary concentration of 1-hydroxypyrene-glucuronide, a metabolite of pyrene, increased significantly in ten subjects who had ingested charbroiled ground beef. We now report the time course and interindividual variation of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) concentration in the urine samples from these ten subjects. PhIP concentration was determined in both untreated and alkali-hydrolyzed urine to obtain estimates of the proportion of conjugated PhIP metabolites in each subject. PhIP was measured by gas chromatography-negative ion chemical ionization-mass spectrometry after derivatization with pentafluorobenzyl bromide. Ten healthy non-smoking males consumed identical amounts of broiled beef on five consecutive days. The morning after the first day of broiled beef consumption, urinary concentration of PhIP increased 14-38 fold above mean pre-feed concentration of PhIP in individual alkali-hydrolyzed urine samples. Following cessation of broiled beef consumption, urinary PhIP concentration declined to near pre-feed levels within 48-72 hrs. The ratio of total alkali-labile PhIP metabolites to unmetabolized PhIP varied by about 2.7-fold among subjects, ranging from 18:1 to 48:1, suggesting that interindividual differences in PhIP metabolism occur and can be detected by this method. This study of urinary PhIP following ingestion of meat cooked by charbroiling, that contains both HAs and polycyclic aromatic hydrocarbons, extends previous studies of ingestion of pan-fried meat that contains primarily HAs. The results indicate that significant amounts of PhIP are bioavailable from ingestion of charbroiled ground beef and that measurement of proportions of alkali-labile PhIP metabolites and parent PhIP in human urine may yield information on individual metabolism of ingested PhIP.
authors.affiliation: Unit of Gene-Environment Interactions, International Agency for Research on Cancer, 69372 Lyon, France.
authors.forename: M D
authors.initials: MD
authors.lastname: Friesen
authors.forename: N
authors.initials: N
authors.lastname: Rothman
authors.forename: P T
authors.initials: PT
authors.lastname: Strickland
mesh_terms: D000328:Adult; D000468:Alkalies / Q000737:chemistry; D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D002417:Cattle; D015179:Colorectal Neoplasms / Q000652:urine*; D003296:Cooking; D004435:Eating; D006801:Humans; D006868:Hydrolysis; D007093:Imidazoles / Q000652:urine*; D007700:Kinetics; D008297:Male; D013058:Mass Spectrometry; D008460:Meat; D008875:Middle Aged
chemical_list: D000468:Alkalies; D002273:Carcinogens; D007093:Imidazoles; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine