Analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine and DNA strand breaks in white blood cells of occupationally exposed workers: comparison with ambient monitoring, urinary metabolites and enzyme polymorphisms.
The relationship between biomarkers of effect (8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo, HPLC system) and tail extent moment (comet assay)), markers of external and internal exposure, and biomarkers of susceptibility was evaluated for coke-oven and graphite-electrode-producing plant workers exposed to polycyclic aromatic hydrocarbons (PAHs). Mean 8-oxodGuo levels in white blood cells (WBC) of exposed workers were between 1.38 times (coke-oven, n = 20; P < 0.01) and 2.15 times (graphite-electrode-producing plant, n = 30; P < 0.01) higher than levels found in control samples (mean +/- SD 0.52 +/- 0.16 8-oxodGuo/10(5) dGuo, n = 47). The mean tail extent moment in lymphocytes was 1.38 times higher for coke-oven workers (n = 19; P = 0.09) and 3.13 times higher for graphite-electrode-producing plant workers (n = 29; P < 0.01) when compared with controls (mean plus minus SD 2.54 +/- 0.68, n = 32). Elevated tail extent moments (>3.73) were found in the majority (84%) of PAH-exposed workers showing increased DNA adduct levels (>0.78 8-oxodGuo/10(5) dGuo). However, no association (P > 0.05) was found between DNA damage (8-oxodGuo/10(5) dGuo or tail extent moment) in WBC of all PAH-exposed workers and either benzo[a]pyrene levels or the sum of 16 PAH levels in the air at work place. Furthermore, no relation (P > 0.05) could be established between DNA damage in WBC and biomarkers of internal exposure (1-hydroxypyrene (1-OHP) and sum of five hydroxyphenanthrenes (OHPHs)). Higher exposure to airborne pyrene and phenanthrene led to increasing concentrations of the metabolites 1-OHP (P < 0.01) and the sum of five OHPHs (P < 0.01) in the urine of PAH-exposed workers. The polymorphisms of genes CYP1A1, GSTM1, GSTT1 and GSTP1 (biomarkers of susceptibility) showed no association with biomarkers of effect. In conclusion, both biomarkers of effect may be appropriate for further surveillance studies of workers under PAH exposure.
Marczynski
B
B
Research Institute of Occupational Medicine at the Ruhr-University Bochum, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany. marczynski@bgfa.ruhr-uni-bochum.de
Rihs
H-P
HP
Rossbach
B
B
Hölzer
J
J
Angerer
J
J
Scherenberg
M
M
Hoffmann
G
G
Brüning
T
T
Wilhelm
M
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000367:Age Factors; D016022:Case-Control Studies; D020552:Comet Assay; D003367:Cotinine / Q000652:urine; D003401:Creatine / Q000652:urine; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D018736:DNA Adducts; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D005091:Exons; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009153:Mutagens; D016273:Occupational Exposure; D010100:Oxygen / Q000378:metabolism; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects / Q000652:urine; D011110:Polymorphism, Genetic; D012907:Smoking
D000080242:8-Hydroxy-2'-Deoxyguanosine; D003367:Cotinine; D003401:Creatine; D019363:Cytochrome P-450 CYP1A1; D018736:DNA Adducts; D003849:Deoxyguanosine; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; D009153:Mutagens; D010100:Oxygen; D011084:Polycyclic Aromatic Hydrocarbons; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human