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

Abstract

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.

Impact of AhR, CYP1A1 and GSTM1 Genetic Polymorphisms on TP53 R273G Mutations in Individuals Exposed to Polycyclic Aromatic Hydrocarbons

“…This is in consistent with occupational studies on PAH-exposed persons, including coke oven workers (Ovrebo et al, 1998;van Delft et al, 2001;Bin et al, 2008). The results were higher than the investigations performed in West European coke oven workers which revealed lower levels of 1-OHP, not exceeding in average the concentration of 2 μmol/mol creatinine (Ovrebo et al, 1998;van Delft et al, 2001;Marczynski et al, 2002).…”

“…This may be the possible reason for GST null genotype in PAH exposure subjects (Strickland et al 1997). Further, the results might be attributable to the fact that, the lower levels of PAH exposure (Ovrebo et al, 1998;van Delft et al, 2001;Marczynski et al, 2002), exposure of the general population to PAHs may be too intermittent to be detectable with a cross-sectional design. Another possibility is that our study lacked the power to reveal the effect of AhR, CYP1A1 and GSTM polymorphisms on 1-OHP levels in the exposed group, or that these enzymes have tissue specificity for the target organs in PAH exposure subjects.…”

CYP1A1 Gene Polymorphisms: Modulator of Genetic Damage in Coal-Tar Workers

“…In our previous study we observed significant association between GSTM1 and GSTT1 null genotypes and BMN frequencies among coal-tar population (Kumar et al, 2011). However, contrary to our results, some studies reported that CYP1A1 m1 and m2 variants did not show any effect on DNA damage among coke-oven and graphide electrode workers (Marczynski et al, 2002;Chen et al, 2006;Moretti et al, 2007). Mahimkar et al (2010) found no association of CYP1A1 gene polymorphism with MN in exfoliated buccal cells in leukoplakia patients.…”

Integrating Field Analyses with Laboratory Exposures to Assess Ecosystems Health

“…Levels of 8-oxo-deoxyguanosine in white blood cells and DNA damage in lymphocytes were higher in coke-oven workers and graphite electrode-producing plant workers than in control subjects. The polymorphisms of the genes CYP1A1, GSTM1, GSTT1 and GSTP1 showed no association with the biomarkers of effect (Marczynski et al, 2002). Urinary 8-oxodeoxyguanosine levels were higher in 55 Taiwanese topside coke-oven workers than in 162 sideoven coke-oven workers (Wu et al, 2003).…”