Associations Of Urinaiy Polycyclic Aromatic Hydrocarbon With Urinary 8-hydroxydeoxyguanosine And OGG1 Methylation In Peripheral Blood Among Coke Oven Workers

Objective:1.To explore the influence of smoking and Polycyclic aromatic hydrocarbons(PAHs)on urinary 8-hydroxydeoxyguanosine(8-OHdG)in coke oven workers and investigate their dose-dependent relationships.2.To assess the relationship between the OH-PA H s occupational exposure in urine or lifestyle and the methylation of OGG1 in peripheral blood.Methods:The study population is composed by coke oven workers(365)and water treatment workers or property management workers(144),their urinary levels of four PAHs metabolites(included 2-hydroxynathalene,2-hydroxyfluorene,9-hydroxyphenanthrene,1-hydroxypyrene)and 8-OHdG were detected by high performance liquid chromatography.Using pyroseuencing,we analyzed DNA methylation of 4 sites within the OGG1 gene promoter from the peripheral blood.The expression of OGG1 in peripheral blood was measured by RT-PCR.Results:1.The median values of the sum of eight carcinogenic PAHs and BaP in exposed sites were significant higher than control sites(P <0.01).The study found that the urinary PAHs metabolites were significantly elevated in coke oven workers(P <0.01).2.In higher exposure group,the concentration of 8-OHdG higher in urine of 1-hydroxypyrene,2-hydroxynaphthalene and ?OH-PAHs was higher than that in middle exposure group and low exposure group(P <0.05).Multivariate logistic regression analysis revealed that the risk of high levels of urinary 8-OHdG will increase with increasing age,cigarette consumption and levels of urinary 1-hydroxypyrene,and P for trend were all <0.05.Smoking can significantly modify the effects of urinary 1-hydroxypyrene on high concentrations urinary 8-OHdG,during co-exposure to both light or heavy smoking and high 1-hydroxypyrene levels(OR=4.28,95%CI:1.32-13.86 and OR=5.05,95% CI :1.63-15.67,respectively).3.The level of methylation of OGG1 site 1,site 2,site 3,site 4 and average of all sites in exposed group was lower than that control group(P <0.05).The average methylation level of OGG1 were significant differences between higher exposure group of 2-hydroxyfluorene and middle exposure group or low exposure group(P <0.05).The linear regression analysis showed that smoking had a linear relationship with the average of all sites and site 3 of OGG1,and the level of OGG1 methylation was decreased with the increase of smoking(P <0.05).Conclusions:1.Our findings quantitatively demonstrate that workers exposed to polycyclic aromatic hydrocarbons and smoking will cause more serious DNA oxidative damage.2.The methylation level of OGG1 decreased in peripheral blood with High exposure to smoking,it is of great significant to take tobacco control measures to prevent the DNA oxidative damage in the coke oven workers.National Natural Science Foundation of China “The Role of Histone Ubiquitination Key Factor Ring2 in Benzo(a)pyrene Induced Cell Cycle Arrest(No:81273041)”.