LINE-1 And AHRR Promoter Methylation Levels Are Related To The PAHs Exposure In Coke Oven Plant Workers

Objective:1.Using urinary polycyclic aromatic hydrocarbon(PAHs) metabolites2-hydroxynathalene(2-NAP), 2-hydroxyfluorene(2-FLU), 9-hydroxyphenanthrene(9-PHE)and 1-hydroxypyrene(1-OHP) as biomarkers, we evaluate the exposure levels of polycyclic aromatic hydrocarbons metabolites and explore the influenced factors of which about coke oven workers and non-coke oven workers in the coking plant;2.To assess the relationship between the OH-PAHs exposure level in urine and the methylation of LINE-1 and AHRR in peripheral blood and explore the early biomarkers of epigenetic changes in PAHs occupational exposures.Methods:Coke oven workers(n=437) and non-coke oven workers(n=163) admitted to a coking plant were recruited and inquired about some basis subjects. The urine samples were collected and four urinary metabolites were measured by high performance lipid chromatography-fluorescence detection; Using pyrosequencing, we analyzed DNA methylation of 3 Cp G sites within the AHRR gene promoter from the peripheral blood,While 4 Cp G sites within the LINE-1 gene,and the AHRR expression has been tested by RT-PCR.Results:1. The concentrationsmedian of urinary 2-NAP、2-FLU、9-PHE and 1-OHP in coke oven workers(0.725μg/mmol Cr、0.300μg/mmol Cr、0.092μg/mmol Cr、0.059μg/mmol Cr,respectively) were significantly higher than those in control group(0.615μg/mmol Cr、0.197μg/mmol Cr、0.065μg/mmol Cr、0.040μg/mmol Cr,respectively)(P<0.01);2. The concentrationsmedian of urinary 2-NAP、2-FLU、9-PHE and 1-OHP was bounded, it can be divided into high content group and low content group, group as the dependent variable and type of work, smoking, drinking for the independent variables has been done the logistic regression analyze,which showed that with increasing a grade in smoking, resulting that 2-NAP concentrations is high content possibility increase 3.39 times. The concentrationsof urinary 2-NAP、2-FLU、9-PHE、and 1-OHP in coke oven workers is high content possibility,which is respectively 1.67、3.40、2.19 and 2.91 times in non coke oven workers;3.The concentrations of urinary 2-NAP、2-FLU、9-PHE、and 1-OHP was divided into high exposure group(the content of urinary metabolites high than P75), median exposure group(the content of urinary metabolites low than P75 and high than P25) and low exposure group(the content of urinary metabolites low than P25), with increasing the content of 1-OHP and smoking, the methylation of LINE-1 decreased(P<0.05);4. The concentrations of urinary 2-NAP、2-FLU、9-PHE、and 1-OHP was divided into high exposure group(the content of urinary metabolites high than P75),median exposure group(the content of urinary metabolites low than P75 and high than P25) and low exposure group(the content of urinary metabolites low than P25),According to the content ofurinary 2-NAP 、2-FLU 、 9-PHE and 1-OHP, the methylation level of AHRR has no statistical difference; with increasing of smoking index, the methylation of AHRR decreased(P<0.05);5. The concentrationsof urinary 2-NAP、2-FLU、9-PHE、and 1-OHP was divided into high exposure group(the content of urinary metabolites high than P75),median exposure group(the content of urinary metabolites low than P75 and high than P25)and low exposure group(the content of urinary metabolites low than P25),with increasing the content of 2-NAP,AHRR expression decreased.Conclusions:1.The major influenced factors of PAHs concentrations is occupation and smoking.Among polycyclic aromatic hydrocarbons metabolites incoke oven workers’ occupation exposure, increasing of 1-OHP and 2-FLU concentrations are more obvious, while increasing of2-NAP concentrations are more obvious in life-style exposure.2.The methylationlevels of LINE-1 decreased with 1-OHPhighexposure;The methylationlevels of AHRR decreased withincreasing of smoking index.