Study On Correlationship Between Proto-oncogenes Biomarkers And Exposure Time In Nickel Smelting Workers

Objectives:We dissected relationship between environmental factors and DNA oxidative damage and repair,biomarkers of lung cancer,and to show molecular mechanisms of lung cancer induced by nickel compounds,which would provides some scientific data for early prevention and intervention of pulmonary injury in nickel occupational workers.Methods:We researched the workers of Jinchuan Group Co.Ltd by questionnaire investigation and physical examination from June 2011 to January 2014.140 workers were selected from a smelting plant and divided into 7 groups based on working years,with 20 workers in each group.In order to remove age's confounding effect on occupational exposure,a control group of 140 office workers was created and divided in the same way.Peripheral blood?PB?were respectively collected and centrifuged from two groups.ELISA was respectively used to detect the DNA damage indicator 8-hydroxy-2'-deoxyguanosine?8-OHDG?,the DNA damage repair indicators poly ADP-ribose polymerase?PARP?and 8-hydroxy-guanine DNA glycosidase 1?hOGG1?,pulmonary proto-oncogene sonic hedgehog?SHH?and regulatory gene Phosphatidylinositol 3-Kinase?PI3K?and hedgehog interacting protein?HHIP?.Pearson was used to study the effect relationship between the proto-oncogenes biomarkers of nickel workers and the DNA oxidative damage and repair biomarkers.Multiple linear regression model was used to analyze the impact factors of proto-oncogenes biomarkers.Results:?1?The serum concentration of 8-OHDG was significantly greater in smelting workers than in office workers among different working years.It initially increased with working years of smelting workers,peaked at 10-<15 years,and then declined compared with office workers.There were statistical significance between smelting workers and office workers in 10-<15 years?P<0.05?.?2?The serum activity of hOGGl was significantly lower in smelting workers than in office workers among different working years.It initially reduced with working years of smelting workers,peaked at 20-<25 years,and then rose compared with office workers.?3?The plasma concentration of SHH and PI3K was significantly higher in smelting workers than in office workers among different working years?P<0.05 for both?,but the opposite was true for HHIP levels?P<0.05?.SHH and PI3K levels initially increased with working years of smelting workers,peaked at 10-<15 years,and then declined compared with office workers.There were statistical significance between smelting workers and office workers in 10-<15 years?P<0.05 for both?.HHIP levels initially decreased with working years,peaking at 10-<15 years,and then gradually increased.There were statistical significance between smelting workers and office workers in 10-<15 years?P<0.05?.?4?Using Pearson,positive correlations were found between plasma SHH and DNA oxidative damage?r=0.50,P<0.05?in smelting workers.Positive correlations were found between plasma SHH and PARP?r=0.46,P<0.05?and hOGG1?r=0.47,P<0.05?.?5?Building multiple linear regression model about biomarkers of lung cancer,with model fitting shows that HHIP,nickel exposure,PI3K,PARP,hOGG1 and H3K27me3 would affect plasma SHH concentrations.Every independent variable contributes to plasma SHH concentrations as follows:HHIP>nickel exposure>PI3K>PARP>hOGGl>H3K27me3.The final optimal fitting multiple linear regression equation is:Y^=-10.90+0.75 X₁+55.83 X₄+1.80 X₅+0.11 X₆+0.37 X₇+0.39 X₈Conclusion:DNA oxidative damage and inhabitation of DNA damage repair by nickel compounds provide a condition for development of cancer.10-<15 years was a key period for DNA damage and development of lung cancer.20-<25 years was the most serious stage for inhabitation of DNA damage repair.Positive correlations were found between plasma SHH and DNA oxidative damage in smelting workers.The results show exposure to nickel compounds was associated with evidence of increased lung cancer.Building multiple linear regression model about biomarkers of lung cancer,with model fitting shows that many factors would affect plasma SHH concentrations,such as HHIP,nickel exposure,PI3K,PARP,hOGG1 and H3K27me3.Every independent variable devotes to plasma SHH concentrations as follows:HHIP>nickel exposure>PI3K>PARP>hOGGl>H3K27me3.The final optimal fitting multiple linear regression equation is:Y^=-10.90+0.75 X₁+55.83 X₄+1.80 X₅+0.11 X₆+0.37 X₇+0.39 X₈...