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CYP1A1 methylation mediates the effect of smoking and occupational polycyclic aromatic hydrocarbons co-exposure on oxidative DNA damage among Chinese coke-oven workers.


ABSTRACT:

Background

Multiple 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.

Methods

We 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.

Results

We 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.

Conclusions

Our 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.

SUBMITTER: Liu Y 

PROVIDER: S-EPMC6664755 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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CYP1A1 methylation mediates the effect of smoking and occupational polycyclic aromatic hydrocarbons co-exposure on oxidative DNA damage among Chinese coke-oven workers.

Liu Yanli Y   Li Xuejing X   Zhang Bin B   Fu Ye Y   Yang Aimin A   Zhang Hongjie H   Zhang Huitao H   Niu Yingying Y   Nie Jisheng J   Yang Jin J  

Environmental health : a global access science source 20190729 1


<h4>Background</h4>Multiple 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.<h4>Methods</h4>We explored the associations betwe  ...[more]

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