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Association Between MGMT And BRCA1 Gene Methylation And DNA Damage In Peripheral Blood Lymphocytes Among Nickel Workers

Posted on:2012-05-08Degree:MasterType:Thesis
Country:ChinaCandidate:Q F GuoFull Text:PDF
GTID:2154330332996256Subject:Occupational and Environmental Health
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Objective: To investigate the association between MGMT and BRCA1 Gene Methylation and DNA damage in peripheral blood Lymphocytes among nickel workers;to approach mechanism of DNA damage in peripheral blood lymphocytes;MGMT methylation and BRCA1 methylation regard as biomarkers of nickel workers.Methods: 165 nickel workers in certain steel factory were selected and divided into three groups: 60 steelmakers , 40 rollers and 65 slaggers.In addition,67 workers at water treatment,without exposure to nickel were matched with those exposed workers by age ,workage, self-reported cigarette smoking and smoking. Flame atomic absorption was used to examine the concentration of nickel in workplaces and dimethylglyoxime spectrophotometry was used to examine urine concentration of nickel. Comet assay was conducted in DNA damage of peripheral lymphocyte isolated from all participating subjects.MSP was conducted to the rate of methylation in MGMT and BRCA1.Results:Compare to the control,OTM of three exposed groups were obviously higher in periphera blood(P<0.01),but there were no significant differences in three exposed groups.Ratio of MGMT methylation of steelmakers is 76.7%, ratio of MGMT methylation of slaggers is 75.4%, ratio of MGMT methylation of steelmakers is 75%, and the control is 55.2%.Tendency analysis increased significantly in the three exposed groups and the control group(χ2=8.684, P=0.003). Ratio of MGMT methylation of three exposed groups were higher than the control group(P<0.05).OTM of cases of MGMT methylation was higher than it of cases of no MGMT methylation in each group(P<0.05). Tendency analysis increased significantly in groups of different urine concentration in MGMT methylation(χ2=14.129,P<0.01).Compare to the lowest urine concentration group,the other two higher urine concentration groups were higher,OR values were 1.882(95%CI 1.280-2.766)and 3.195(95%CI 1.464-6.973).Methylation rate of BRCA1 gene in steelmakers(81.7%) was higher than it of control group(62.7%), OR values was 2.035(95%CI 1.097-3.775). Methylation rate of BRCA1 gene in slaggers(81.5%) was higher than it of control group, OR values was 2.021(95%CI 1.112-3.675). Tendency analysis increased significantly in the three exposed groups and the control group(χ2=9.013, P=0.029). OTM of cases of BRCA1 methylation was higher than it of cases of no BRCA1 methylation in each exposed group(P<0.05). There was significant difference in three groups divided according to workage(P<0.05),tendency analysis increased significantly in the three different workage groups . Compare to the lowest urine concentration group,methylation rate of the highest urine concentration group was higher(P<0.05).Conclusion: Nickel contacting could result in DNA Damage in peripheral blood Lymphocytes, MGMT gene methylation and BRCA1 methylation may be associated with DNA damage in peripheral blood Lymphocytes among nickel workers.
Keywords/Search Tags:DNA damage, promoter CpG island hypermethyaltion, MGMT gene, BRCA1 gene, occupational exposure to nickel
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