Objective To study the role of aryl hydrocarbon receptor (AhR) gene expression in oxidative DNA damage induced by polycyclic aromatic hydrocarbons (PAH) in coke oven workers.
Methods A total of 312 coke oven workers from a steel plant were selected to complete a questionnaire survey on general information and have blood and urine samples collected. Urinary concentrations of four PAH metabolites (PAH biomarkers), including 2-hydroxynaphthalene (2-NAP), 2-hydroxyfluorene (2-FLU), 9-phenanthrol (9-PHE), and 1-pyrenol (1-OHP), and 8-hydroxydeoxyguanosine (8-OHdG, DNA oxidative damage indicator) were determined by high performance liquid chromatography; AhR expression was measured by reverse transcription PCR.
Results The workers were divided into low, medium, and high exposure groups according to urinary 1-OHP level (< P25, P25-P75, and >P75). With the increasing of 1-OHP level, the levels of 2-FLU and 9-PHE increased. The multiple logistic regression analysis results showed that urinary 1-OHP level was associated with AhR expression (OR=2.08, 95%CI:1.21-3.58) and 8-OHdG level (OR=2.98, 95%CI:1.65-5.32) after adjusted for sex, age, smoking, drinking, 2-NAP, 2-FLU, and 9-PHE in a liner dose-response relationship (Ptrend < 0.05). In addition, AhR expression was positively related to 8-OHdG level (OR=2.18, 95%CI:1.35-3.51) in a linear dose-response relationship (Ptrend=0.001). The mediation analysis results found the regression coefficients of a, b, c, and c' (1.59, 0.32, 0.36 and 1.61, respectively) were of statistical significance (P < 0.05). Specifically, c and c' were both significant, indicating mediation effect and direct effect; ab had a same sign with c' indicating partial mediation effect. So AhR expression played a partial mediation effect in PAH-related oxidative DNA damage.
Conclusion There are linear dose-response relationships of PAH exposure with AhR expression and oxidative DNA damage, and the effect of PAH exposure on DNA oxidative damage may be mediated by AhR expression.
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