PAH-DNA adducts in a Chinese population: relationship to PAH exposure, smoking and polymorphisms of metabolic and DNA repair genes

• Published in: Biomarkers Vol. 13; no. 1; pp. 27 - 40
• Main Authors: Hu, Yu, Li, Gang, Xue, Xiaonan, Zhou, Zongcan, Li, Xiaomei, Fu, Juanling, Cohen, Beverly, Roy, Nirmal, Li, Donghui, Sun, Jianya, Nan, Peihong, Tang, Moon-Shong, Qu, Qingshan
• Format: Journal Article
• Language: English
• Published: London Informa UK Ltd 01.01.2008; Taylor & Francis
• Subjects: Adult; Asian Continental Ancestry Group; Biological and medical sciences; biomarkers; Biomarkers - blood; Carcinogenesis, carcinogens and anticarcinogens; Chemical agents; China; Cotinine - blood; Cotinine - urine; Cytochrome P-450 CYP1A1 - genetics; DNA Adducts - blood; DNA Repair - genetics; Environmental exposure; Environmental Exposure - analysis; Epoxide Hydrolases - genetics; Female; Gardening; genetic susceptibility; Glutathione Transferase - genetics; Humans; Male; Medical sciences; Occupational Exposure - analysis; polycyclic aromatic hydrocarbons; Polycyclic Aromatic Hydrocarbons - blood; Polymorphism, Genetic; Smoking - blood; Tobacco, tobacco smoking; Toxicology; Tumors; Xeroderma Pigmentosum Group D Protein - genetics; Asia; China; Human; Environmental exposure; Genetic variability; Hydrocarbon; biomarkers; Tobacco smoking; Biological marker; Genotype; Exposure; Polycyclic aromatic compound; Metabolism; polycyclic aromatic hydrocarbons; DNA repair; Repair gene; Carcinogen; Sensitivity resistance; DNA; Molecular epidemiology; Environment; Genetics; genetic susceptibility; Molecular adduct; Polymorphism
• ISSN: 1354-750X; 1366-5804
• DOI: 10.1080/13547500701671895

Abstract The present study was conducted in a Chinese population to evaluate the usefulness and sensitivity of PAH-DNA adduct as a biomarker of PAH exposure, and to examine the potential effects of smoking and polymorphisms of responsive genes on DNA adduct formation induced by PAH exposure. The polymorphisms of genes examined include GSTM1, GSTT1, CYP1A1, microsomal epoxide hydrolase (mEH) and excision repair cross-complementary group 2 (ERCC2). A total of 194 subjects with a broad range of PAH exposures were recruited, including 116 occupationally exposed workers, 49 metropolitan residents and 29 suburban gardeners. A significant exposure-response relationship was observed between PAH exposure and DNA adducts in leukocytes across the entire group of subjects (p<0.0001). The levels of PAH-DNA adducts in the subgroup with lowest occupational exposure to PAHs (<0.1µg BaP m−3) was significantly higher than that in metropolitan residents and suburban gardeners. However, no significant difference was detected between residents and gardeners, with mean BaP concentrations of 0.028 and 0.011µg m−3, respectively. The polymorphisms of genes examined failed to show significant effects on PAH-induced adduct formation except ERCC2 Lys751Gln genotypes. A significantly higher level of PAH-DNA adduct was found in subjects with wild-type ERCC2 than those who have either heterozygous or homozygous variant alleles (p<0.01). Smoking, age and gender did not substantially contribute to PAH-induced DNA adduct formation in this study. The study suggests that PAH-DNA adducts may serve as a reliable biomarker of PAH exposure in occupational settings but may not be sensitive enough to be used in populations with environmental exposures to PAHs.