PAH-DNA adducts in a Chinese population: relationship to PAH exposure, smoking and polymorphisms of metabolic and DNA repair genes.
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 (< 0.1 microg 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 0.011 microg 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.
Hu
Yu
Y
Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA.
Li
Gang
G
Xue
Xiaonan
X
Zhou
Zongcan
Z
Li
Xiaomei
X
Fu
Juanling
J
Cohen
Beverly
B
Roy
Nirmal
N
Li
Donghui
D
Sun
Jianya
J
Nan
Peihong
P
Tang
Moon-Shong
MS
Qu
Qingshan
Q
D000328:Adult; D044466:Asian People; D015415:Biomarkers / Q000097:blood*; D002681:China; D003367:Cotinine / Q000097:blood / Q000652:urine; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D018736:DNA Adducts / Q000097:blood*; D004260:DNA Repair / Q000235:genetics*; D004781:Environmental Exposure / Q000032:analysis; D004851:Epoxide Hydrolases / Q000235:genetics; D005260:Female; D051639:Gardening; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008297:Male; D016273:Occupational Exposure / Q000032:analysis; D011084:Polycyclic Aromatic Hydrocarbons / Q000097:blood*; D011110:Polymorphism, Genetic; D012907:Smoking / Q000097:blood*; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
D015415:Biomarkers; D003367:Cotinine; D019363:Cytochrome P-450 CYP1A1; D018736:DNA Adducts; D004851:Epoxide Hydrolases; D005982:Glutathione Transferase; D011084:Polycyclic Aromatic Hydrocarbons; D051759:Xeroderma Pigmentosum Group D Protein; C095911:polycyclic aromatic hydrocarbons-DNA adduct; C413545:glutathione S-transferase T1; C497292:ERCC2 protein, human