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Impacts Of PAHs Exposure On The Metabolic Enzyme Gene Methylation And Expression Level Of Peripheral Blood In Coke Oven Worker

Posted on:2017-02-03Degree:MasterType:Thesis
Country:ChinaCandidate:M WuFull Text:PDF
GTID:2284330503463244Subject:Occupational and Environmental Health
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Objective:To analysis the relationship between the peripheral blood cells in the aromatic hydrocarbon hydroxylase(CYP1A1) and glutathione s transferase(GSTP) gene DNA promoter Cp G island methylation level the m RNA level change after exposed to polycyclic aromatic hydrocarbons(PAHs) of coke oven workers, in order to search for early biomarkers effect of popμlation health hazard exposure to PAHs, provide the basis for protection of public health. Methods:Selected 118 occupational in the coking plant workers(exposed group) and 63 water supply factory workers(control group) as the research object, the exposed group can be divided into furnace top, side and bottom three exposure levels, to face to face survey the age, gender, age, type of work, smoking, drinking, education situation, living habits and personal history family history and medication history, etc. as questionnaire,, and then collating data entry Epidata database. Workers And then detected the hydroxy pyrene(1-OH-Py) of urine by high performance liquid chromatography(HPLC) method 1-hydroxy pyrene(1-OH-Py) content; Fasting venous blood was collected in the morning(EDTA anticoagμlant), using fluorescence quantitative polymerase chain reaction(QT- PCR) to detect in the peripheral blood cells CYP1A1, GSTP gene promoter Cp G island methylation level and m RNA expression level, statistical analysis the ralationship between PAHs exposure level and expression and methylation level of CYP1A1 and GSTP gene. Resμlts:The first part: Urinary 1-OH-Py level increased with the level of exposure, and compared with control group, the level of contact group 1-OH-Py level increased significantly, the difference was statistically significant(P<0.05);Furnace side group 1-OH-Py level is a significant rise in furnace bottom group, the difference was statistically significant(P<0.05);Top group 1-OH-Py level than the control group with a significant rise in furnace bottom group, but with the furnace side there was no statistically significant difference.Work with 1-OH-Py levels in urine were positively correlated(r=0.364, P<0.001).The second part: The CYP1A1 gene DNA start promoter region Cp G island methylation level of bottom, side of the furnace and the furnace top workers was lower than the control group and CYP1A1 methylation levels in furnace bottom and furnace side workers was significantly lower than that of control group(P < 0.05)..CYP1A1 m RNA level of exposure group is lower than the control group, each exposure group and control group differences were statistically significant(P<0.05).As the urine increased, the level of 1-OH-Py, CYP1A1 methylation level tends to rise, and when reducing, and the m RNA level down.CYP1A1 m RNA level and a negative correlation between 1-OH-Py(r=0.269, P<0.001).The third part: The exposured group GSTP gene DNA promoter region Cp G island methylation level is lower than the control group, the difference was statistically significant(P<0.05),and also the level of gene expression. CYP1A1 methylation and GSTP methylation level was positively correlated(r = 0.831, P < 0.001); and GSTP m RNA showed a negative correlation(r =-0.244, P = 0.002); Between the GSTP methylation and m RNA level showed a negative correlation(r=--0.18, P = 0.027); Between CYP1A1 and GSTP m RNA was positively correlated(r=0.241, P = 0.001). Conclusions:(1) Coke oven workers exposure to B(a)P have a positive impact on the level of 1-OH-Py in urine, the level of 1-OH-Py can be very good as an internal exposure biomarker evaluation of coke oven workers B(a)P exposure level.(2) With the increase of 1-OH-Py in urine, the expression level of CYP1A1 in the peripheral blood of coke oven workers was significantly lower, and the methylation level was lower, but not obvious. CYP1A1 expression level may be used as a biomarker for occupational exposure to harmful substances in order to provide a basis for the protection of high-risk groups.(3) With the increase of 1-OH-Py in urine, the expression level of Metabolic detoxification enzymes of B(a) P in peripheral blood of coke oven workers was down regulated and reduced the level of methylation, gene expression level and the DNA start promoter Cp G island methylation level was negatively correlated, GSTP methylation level may be used as a biomarker for occupational exposure to harmful substances in order to provide a basis for the protection of high-risk groups.
Keywords/Search Tags:Polycyclic aromatic hydrocarbons, CYP1A1, GSTP, The expression level, Gene methylation
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