title: Genetic polymorphisms in metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine.
abstract: Heterocyclic amines (HCAs) are naturally produced during common cooking processes for meats and fish. HCAs are metabolized by various enzymes, including cytochromes P450, N-acetyl transferases, and sulfotransferases, and their bioactivated metabolites are considered to bind to DNA or protein to show carcinogenic effects. More than 20 HCAs have been identified, of which 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is classified as 'reasonably anticipated to be a human carcinogen' to develop cancers in breast, colon and prostate. The purpose of this study was to evaluate human exposure levels of PhIP and to understand the role of genetic polymorphisms of enzymes on PhIP metabolism. Urine samples were collected from subjects (n = 100) before 3-day meat-restricted diets. Subjects consumed grilled chicken, and their blood and urine were collected before and after the administration of the chickens to investigate genetic polymorphisms and PhIP levels. The mean PhIP levels were 4.22 ± 0.12, 0.61 ± 0.19 and 22.64 ± 1.00 pg ml(-1) in urine under normal conditions and before and after chicken administration, respectively. Among 21 Single-nucleotide polymorphisms (SNP) of CYP1A1, CYP1A2, NATs and UGTs investigated in this study, genotypic groups of CYP1A1/T6235C (MSP I) and CYP1A2/-2467delT showed significant differences in PhIP excretion (P < 0.05). These results suggest that genetic polymorphisms might affect PhIP metabolism, which could improve understanding of populations subject to PhIP-derived health risk.
authors: Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk, 363-951, Korea.
authors: Dojung
authors: D
authors: Kim
authors: Young-Joo
authors: YJ
authors: Lee
authors: Heui-Young
authors: HY
authors: Ryu
authors: Jin-Hee
authors: JH
authors: Lee
authors: Hyun-Kyung
authors: HK
authors: Kim
authors: Eunhee
authors: E
authors: Kim
authors: Jae-Dong
authors: JD
authors: Moon
authors: Dong Deuk
authors: DD
authors: Chang
authors: Hae-Seong
authors: HS
authors: Yoon
mesh_terms: D000293:Adolescent; D000328:Adult; D002273:Carcinogens / Q000378:metabolism*; D003296:Cooking; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004435:Eating; D004781:Environmental Exposure / Q000032:analysis; D020022:Genetic Predisposition to Disease; D006801:Humans; D007093:Imidazoles / Q000378:metabolism*; D008297:Male; D008461:Meat Products; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D002273:Carcinogens; D007093:Imidazoles; D003577:Cytochrome P-450 Enzyme System; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine