Effects of genetic polymorphisms in metabolic enzymes on the relationships between 8-hydroxydeoxyguanosine levels in human leukocytes and urinary 1-hydroxypyrene and 2-naphthol concentrations

Yong Dae Kim, Chul Ho Lee, Hongmei Nan, Jong Won Kang, Heon Kim

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32 Citations (Scopus)

Abstract

This study was designed to investigate the relationship between environmental exposure to polycyclic aromatic hydrocarbons (PAHs) and oxidative stress, and to evaluate the effects of cigarette smoking and the genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, NAT2 and UGT1A6 on the relationship. The subjects of this study were 105 healthy Korean males without occupational exposure to PAHs. The 8-hydroxydeoxyguanosine (8-OHdG) level in leukocytes, and urinary 1-hydroxypyrene (1-OHP) and 2-naphthol concentrations, were measured by high-performance liquid chromatography. Genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, NAT2 and UGT1A6 were identified by PCR and PCR-RFLP methods. The 8-OHdG level showed a significant correlation with the 1-OHP concentration in all subjects (p< .001) and in smokers (p< .01), and with the 2-naphthol level in non-smokers (p< .01). The 8-OHdG level was significantly higher in smoking rapid acetylators than in smoking slow or intermediate acetylators, and in individuals with the UGT1A6 wild-type than in those with the UGT1A6 mutant genotype. Significant positive correlations between 8-OHdG and 1-OHP concentrations were found in subjects with every genotype of the CYP1A1 and CYP2E1 genes, with the GSTM1 null-type, with the NAT2 genotype of a rapid acetylator, and with the UGT1A6 wild-type, respectively. The urinary 2-naphthol level significantly correlated with the 8-OHdG level only in subjects with the GSTM1 null-type. In conclusion, there is a significant correlation between the 8-OHdG level in leukocytes and the urinary 1-OHP concentration in the population not occupationally exposed to PAHs. This relationship is affected by genetic polymorphisms in PAH metabolic enzymes.

Original languageEnglish (US)
Pages (from-to)160-167
Number of pages8
JournalJournal of Occupational Health
Volume45
Issue number3
DOIs
StatePublished - May 1 2003
Externally publishedYes

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Polycyclic Aromatic Hydrocarbons
Genetic Polymorphisms
Cytochrome P-450 CYP2E1
Cytochrome P-450 CYP1A1
Leukocytes
Smoking
Genotype
Enzymes
Polymerase Chain Reaction
Environmental Exposure
Occupational Exposure
Restriction Fragment Length Polymorphisms
Oxidative Stress
High Pressure Liquid Chromatography
2-naphthol
8-oxo-7-hydrodeoxyguanosine
Population
Genes

Keywords

  • 1-hydroxypyrene
  • 2-naphthol
  • 8-hydroxydeoxyguanosine
  • Metabolic enzyme
  • Polymorphism

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health

Cite this

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title = "Effects of genetic polymorphisms in metabolic enzymes on the relationships between 8-hydroxydeoxyguanosine levels in human leukocytes and urinary 1-hydroxypyrene and 2-naphthol concentrations",
abstract = "This study was designed to investigate the relationship between environmental exposure to polycyclic aromatic hydrocarbons (PAHs) and oxidative stress, and to evaluate the effects of cigarette smoking and the genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, NAT2 and UGT1A6 on the relationship. The subjects of this study were 105 healthy Korean males without occupational exposure to PAHs. The 8-hydroxydeoxyguanosine (8-OHdG) level in leukocytes, and urinary 1-hydroxypyrene (1-OHP) and 2-naphthol concentrations, were measured by high-performance liquid chromatography. Genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, NAT2 and UGT1A6 were identified by PCR and PCR-RFLP methods. The 8-OHdG level showed a significant correlation with the 1-OHP concentration in all subjects (p< .001) and in smokers (p< .01), and with the 2-naphthol level in non-smokers (p< .01). The 8-OHdG level was significantly higher in smoking rapid acetylators than in smoking slow or intermediate acetylators, and in individuals with the UGT1A6 wild-type than in those with the UGT1A6 mutant genotype. Significant positive correlations between 8-OHdG and 1-OHP concentrations were found in subjects with every genotype of the CYP1A1 and CYP2E1 genes, with the GSTM1 null-type, with the NAT2 genotype of a rapid acetylator, and with the UGT1A6 wild-type, respectively. The urinary 2-naphthol level significantly correlated with the 8-OHdG level only in subjects with the GSTM1 null-type. In conclusion, there is a significant correlation between the 8-OHdG level in leukocytes and the urinary 1-OHP concentration in the population not occupationally exposed to PAHs. This relationship is affected by genetic polymorphisms in PAH metabolic enzymes.",
keywords = "1-hydroxypyrene, 2-naphthol, 8-hydroxydeoxyguanosine, Metabolic enzyme, Polymorphism",
author = "Kim, {Yong Dae} and Lee, {Chul Ho} and Hongmei Nan and Kang, {Jong Won} and Heon Kim",
year = "2003",
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volume = "45",
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journal = "Journal of Occupational Health",
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publisher = "Japan Society for Occupational Health",
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T1 - Effects of genetic polymorphisms in metabolic enzymes on the relationships between 8-hydroxydeoxyguanosine levels in human leukocytes and urinary 1-hydroxypyrene and 2-naphthol concentrations

AU - Kim, Yong Dae

AU - Lee, Chul Ho

AU - Nan, Hongmei

AU - Kang, Jong Won

AU - Kim, Heon

PY - 2003/5/1

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N2 - This study was designed to investigate the relationship between environmental exposure to polycyclic aromatic hydrocarbons (PAHs) and oxidative stress, and to evaluate the effects of cigarette smoking and the genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, NAT2 and UGT1A6 on the relationship. The subjects of this study were 105 healthy Korean males without occupational exposure to PAHs. The 8-hydroxydeoxyguanosine (8-OHdG) level in leukocytes, and urinary 1-hydroxypyrene (1-OHP) and 2-naphthol concentrations, were measured by high-performance liquid chromatography. Genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, NAT2 and UGT1A6 were identified by PCR and PCR-RFLP methods. The 8-OHdG level showed a significant correlation with the 1-OHP concentration in all subjects (p< .001) and in smokers (p< .01), and with the 2-naphthol level in non-smokers (p< .01). The 8-OHdG level was significantly higher in smoking rapid acetylators than in smoking slow or intermediate acetylators, and in individuals with the UGT1A6 wild-type than in those with the UGT1A6 mutant genotype. Significant positive correlations between 8-OHdG and 1-OHP concentrations were found in subjects with every genotype of the CYP1A1 and CYP2E1 genes, with the GSTM1 null-type, with the NAT2 genotype of a rapid acetylator, and with the UGT1A6 wild-type, respectively. The urinary 2-naphthol level significantly correlated with the 8-OHdG level only in subjects with the GSTM1 null-type. In conclusion, there is a significant correlation between the 8-OHdG level in leukocytes and the urinary 1-OHP concentration in the population not occupationally exposed to PAHs. This relationship is affected by genetic polymorphisms in PAH metabolic enzymes.

AB - This study was designed to investigate the relationship between environmental exposure to polycyclic aromatic hydrocarbons (PAHs) and oxidative stress, and to evaluate the effects of cigarette smoking and the genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, NAT2 and UGT1A6 on the relationship. The subjects of this study were 105 healthy Korean males without occupational exposure to PAHs. The 8-hydroxydeoxyguanosine (8-OHdG) level in leukocytes, and urinary 1-hydroxypyrene (1-OHP) and 2-naphthol concentrations, were measured by high-performance liquid chromatography. Genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, NAT2 and UGT1A6 were identified by PCR and PCR-RFLP methods. The 8-OHdG level showed a significant correlation with the 1-OHP concentration in all subjects (p< .001) and in smokers (p< .01), and with the 2-naphthol level in non-smokers (p< .01). The 8-OHdG level was significantly higher in smoking rapid acetylators than in smoking slow or intermediate acetylators, and in individuals with the UGT1A6 wild-type than in those with the UGT1A6 mutant genotype. Significant positive correlations between 8-OHdG and 1-OHP concentrations were found in subjects with every genotype of the CYP1A1 and CYP2E1 genes, with the GSTM1 null-type, with the NAT2 genotype of a rapid acetylator, and with the UGT1A6 wild-type, respectively. The urinary 2-naphthol level significantly correlated with the 8-OHdG level only in subjects with the GSTM1 null-type. In conclusion, there is a significant correlation between the 8-OHdG level in leukocytes and the urinary 1-OHP concentration in the population not occupationally exposed to PAHs. This relationship is affected by genetic polymorphisms in PAH metabolic enzymes.

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