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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
- Source :
- Environmental Health, Vol 18, Iss 1, Pp 1-9 (2019), Environmental Health
- Publication Year :
- 2019
- Publisher :
- BMC, 2019.
-
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. Electronic supplementary material The online version of this article (10.1186/s12940-019-0508-0) contains supplementary material, which is available to authorized users.
- Subjects :
- Adult
Male
China
medicine.medical_specialty
Coke oven
Health, Toxicology and Mutagenesis
Oxidative dna damage
03 medical and health sciences
chemistry.chemical_compound
lcsh:RC963-969
Occupational Exposure
Internal medicine
Cytochrome P-450 CYP1A1
medicine
polycyclic compounds
Humans
Deoxyguanosine
Cytochrome P4501A1
0303 health sciences
DNA methylation
business.industry
Research
lcsh:Public aspects of medicine
Smoking
Public Health, Environmental and Occupational Health
030311 toxicology
lcsh:RA1-1270
Methylation
Middle Aged
Pah exposure
Polycyclic aromatic hydrocarbons
Oxidative Stress
Cross-Sectional Studies
Endocrinology
chemistry
Oxidative DNA damage
lcsh:Industrial medicine. Industrial hygiene
Pyrosequencing
Female
Co exposure
business
DNA Damage
Subjects
Details
- Language :
- English
- Volume :
- 18
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Environmental Health
- Accession number :
- edsair.doi.dedup.....c86df8853f96bc408a84ab0d754cca44