Affordable Access

deepdyve-link deepdyve-link
Publisher Website

Genetic polymorphisms in metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine.

Authors
  • Kim, Dojung1
  • Lee, Young-Joo
  • Ryu, Heui-Young
  • Lee, Jin-Hee
  • Kim, Hyun-Kyung
  • Kim, Eunhee
  • Moon, Jae-Dong
  • Chang, Dong Deuk
  • Yoon, Hae-Seong
  • 1 Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk, 363-951, Korea. , (North Korea)
Type
Published Article
Journal
Journal of Applied Toxicology
Publisher
Wiley (John Wiley & Sons)
Publication Date
Jan 01, 2013
Volume
33
Issue
1
Pages
63–70
Identifiers
DOI: 10.1002/jat.1712
PMID: 22131055
Source
Medline
License
Unknown

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.

Report this publication

Statistics

Seen <100 times