TY - JOUR
T1 - Metabolites of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) in human urine after consumption of charbroiled or fried beef
AU - Strickland, Paul T.
AU - Qian, Zheng
AU - Friesen, Marlin D.
AU - Rothman, Nathaniel
AU - Sinha, Rashmi
N1 - Funding Information:
The authors acknowledge and thank Drs. James Felton and Mark Knize (Lawrence Livermore National Laboratory) for PhIP analysis of beef samples; and Dr. Steven Tannenbaum and Ms. Laura Trudel (Massachusetts Institute of Technology) for providing monoclonal antibody 4F5. Research supported in part by DHHS grants P01-ES06052 and P30-ES03819.
PY - 2002/9/30
Y1 - 2002/9/30
N2 - 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 N2-OH-PhIP-N2-glucuronide, PhIP-N2-glucuronide, N2-OH-PhIP-N3-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 7.7μg 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 48-72h. 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<0.0001) with the amount of fried meat ingested. Additional studies have measured PhIP metabolites in subjects consuming their normal (unrestricted) diet. PhIP was detected in acid-hydrolyzed urine from 20 to 50% of these subjects, depending on ethnic group. Taken together, these studies indicate that significant amounts of PhIP are bioavailable from ingestion of fried or char-broiled meats, and that urinary PhIP metabolites reflect recent (12-24h) ingestion. Furthermore, significant interindividual differences in the amounts of urinary PhIP metabolite excreted are observed following ingestion of similar amounts of PhIP. These differences do not correlate with interindividual differences in excretion of urinary pyrene metabolites in the same individuals after ingestion of char-broiled beef, indicating that levels of PhIP and pyrene metabolites in human urine are mediated by compound-specific metabolic factors.
AB - 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 N2-OH-PhIP-N2-glucuronide, PhIP-N2-glucuronide, N2-OH-PhIP-N3-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 7.7μg 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 48-72h. 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<0.0001) with the amount of fried meat ingested. Additional studies have measured PhIP metabolites in subjects consuming their normal (unrestricted) diet. PhIP was detected in acid-hydrolyzed urine from 20 to 50% of these subjects, depending on ethnic group. Taken together, these studies indicate that significant amounts of PhIP are bioavailable from ingestion of fried or char-broiled meats, and that urinary PhIP metabolites reflect recent (12-24h) ingestion. Furthermore, significant interindividual differences in the amounts of urinary PhIP metabolite excreted are observed following ingestion of similar amounts of PhIP. These differences do not correlate with interindividual differences in excretion of urinary pyrene metabolites in the same individuals after ingestion of char-broiled beef, indicating that levels of PhIP and pyrene metabolites in human urine are mediated by compound-specific metabolic factors.
KW - Biomarker
KW - Dietary carcinogens
KW - HPLC
KW - Heterocyclic amines
KW - PhIP
KW - Urine metabolites
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U2 - 10.1016/S0027-5107(02)00163-X
DO - 10.1016/S0027-5107(02)00163-X
M3 - Article
C2 - 12351156
AN - SCOPUS:0037201539
SN - 0027-5107
VL - 506-507
SP - 163
EP - 173
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
ER -