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Journal of Occupational Health
Article . 2003 . Peer-reviewed
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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

Authors: Jong Won Kang; Hongmei Nan; Heon Kim; Chul-Ho Lee; Yong-Dae Kim;

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

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, et al. Department of Preventive Medicine, College of Medicine, Chungbuk National University, South Korea—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 nonsmokers (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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Keywords

Male, Guanine, Polymorphism, Genetic, Pyrenes, Genotype, Arylamine N-Acetyltransferase, Smoking, Cytochrome P-450 CYP2E1, Naphthols, Polymerase Chain Reaction, 8-Hydroxy-2'-Deoxyguanosine, Cytochrome P-450 CYP1A1, Leukocytes, Humans, Regression Analysis, Glucuronosyltransferase, Biomarkers, Chromatography, High Pressure Liquid, Polymorphism, Restriction Fragment Length, Glutathione Transferase

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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
35
Average
Top 10%
Top 10%
gold