Abstract
BackgroundMultiple factors, including co-exposure between lifestyle and environmental risks, are important in susceptibility to oxidative DNA damage. However, the underlying mechanism is not fully understood. This study was undertaken to evaluate whether Cytochrome P4501A1 (CYP1A1) methylation can mediate the co-exposure effect between smoking and occupational polycyclic aromatic hydrocarbons (PAH) in development of oxidative DNA damage.MethodsWe explored the associations between smoking and occupational PAH co-exposure effect, CYP1A1 methylation and oxidative DNA damage among 500 workers from a coke-oven plant in China. Urine biomarkers of PAH exposure (1-hydroxypyrene, 1-OHP; 2-hydroxynaphthalene, 2-NAP; 2-hydroxyfluorene, 2-FLU; and 9-hydroxyphenanthren, 9-PHE) and a marker of oxidative DNA damage (8-hydroxy- 2′- deoxyguanosine, 8-OHdG) were measured by high performance liquid chromatography. CYP1A1 methylation was measured by pyrosequencing. Finally, mediation analysis was performed to investigate whether CYP1A1 methylation mediated smoking and occupational PAH co-exposure effect on oxidative DNA damage.ResultsWe observed significant associations of smoking and 1-OHP co-exposure with CYP1A1 hypomethylation (OR: 1.87, 95% CI: 1.01–3.47) and high 8-OHdG (OR: 2.13, 95% CI: 1.14–3.97). There was a significant relationship between CYP1A1 hypomethylation and high 8-OHdG (1st vs. 3rd tertile = 1.58, 95% CI: 1.01–2.47, P for trend = 0.046). In addition, mediation analysis suggested CYP1A1 hypomethylation could explain 13.6% of effect of high 8-OHdG related to smoking and 1-OHP co-exposure.ConclusionsOur findings suggested that the co-exposure effect of smoking and occupational PAH could increase the risk of oxidative DNA damage by a mechanism partly involving CYP1A1 hypomethylation.
Highlights
Oxidative DNA damage induced by reactive oxygen species (ROS) plays a pivotal role in the nosogenesis of respiratory disease such as lung cancer and asthma [1, 2]
After adjusting covariates, we found that smoking and 1-OHP co-exposure was associated with Cytochrome P4501A1 (CYP1A1) hypomethylation (P < 0.05)
These results suggested that CYP1A1 hypomethylation may be a potential mediator of smoking and 1-OHP co-exposure effect on the risk of oxidative DNA damage
Summary
Oxidative DNA damage induced by reactive oxygen species (ROS) plays a pivotal role in the nosogenesis of respiratory disease such as lung cancer and asthma [1, 2]. Previous studies have shown that 8-hydroxy- 2′- deoxyguanosine (8-OHdG) is a widely accepted biomarker for assessing the extent of oxidative damage to DNA [6]. Lifestyle environmental factors, such as smoking [7,8,9] and polycyclic aromatic hydrocarbons (PAH) exposure [10, 11], have been proved to relate with urine 8-OHdG levels. A challenge remains to fully understand the molecular mechanism of lifestyle environmental factors between smoking and occupational PAH co-exposure effect on oxidative DNA damage. This study was undertaken to evaluate whether Cytochrome P4501A1 (CYP1A1) methylation can mediate the co-exposure effect between smoking and occupational polycyclic aromatic hydrocarbons (PAH) in development of oxidative DNA damage
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