Study On The Biomarkers Of Embryo Lung Development And Its Regulation In Nickel Smelting Workers

OBJECTIVESThe aim of this research was to see what’s the effect of nickel smelting environment exposure on the expression of embryo lung development biomarker Nkx2.1 and regulation factors which have impact on the transcription of Nkx2.1 and epigenetics biomarkers in nickel smelting workers,and provide a possible mechanism of lung cancers induced by nickel compounds with a view of embryo development.METHODSNickel smelting workers group was chosen from male workers of the smeltery unit of the nickel company using diagonal sampling method,while office workers group was chosen from the unexposed administrative office of the company matched with age and sex.Nkx2.1,pSmad2 and H3K27me3 levels were compared in different groups and working years using ELISA method.The difference of these biomarkers was analysed among 7 working-years groups and two kinds of groups,including nickel workers and office workers.And also,the factors affecting these biomarkers were analysed through the multiple regression model,with the combination of the laboratory findings of our previous experiment and the epidemiological information,including social-economics,drinking alcohol,drinking tea and smoking conditions.RESULTS1.With regard to the levels of pSmad2,a statistical difference existed among working-years groups in nickel workers,pSmad2 was positively correlated with working years.And there was no difference in office workers group.Nickel smelting workers were higher than office workers in 3rd,4th,5th,6th and 7th working-years groups(P<0.05).2.H3K27me3 had a statistical difference in nickel and office workers group,and the level of H3K27me3 in nickel workers was lower than office workers(P<0.05).Its level had the inverse association with working years in both nickel workers and office workers.3.For Nkx2.1,there was a statistical difference in working-years groups of nickel smelting workers,and its level was positively correlated with working years.While office workers didn’t show that.For the workers whose working years were larger than 10 and more,Nkx2.1 levels were higher than office workers in the same working-years group(P<0.05).4.In smelting workers,working years was correlated with SOD(negatively correlated,marked as "-"),the repair biomarker of oxidation damage biomarker HP1(-),lipid peroxidation biomarker MDA(positively correlated,marked as "+"),epigenetics biomarker H3K4me3 related to gene activation(+),epigenetics biomarker H3K27me3 related to gene suppression(-),embryo lung development markers Nkx2.1(+),Nkx2.1’s regulation marker pSmad2(+).5.In smelting workers,pSmad2 and H3K4me3 were found to have a correlation with Nkx2.1 positively,while H3K27me3 had an inverse association with Nkx2.1.6.Using the multiple regression model,we also found that working years(+),monthly income per capita(-),drinking alcohol(-),drinking tea(-)were correlated with pSmad2,and working years had the maximum effect on pSmad2 among them.Education level(+),HP1(+),monthly income per capita(+),drinking alcohol(-),drinking tea(-),H3K4me3(-),MDA(-),Nkx2.1(-),pSmad2(-),smoking condition(-)and working years(-)were correlated with H3K27me3,and working years had the maximum effect on H3K27me3 among them.While H3K4me3(+),MDA(+),pSmad2(+),working years(+),drinking alcohol(-),drinking tea(-),education level(-),H3K27me3(-),HP1(-),monthly income per capita(-),smoking(-)and SOD(-)were associated with Nkx2.1,pSmad2,HP1 and working years had larger effect on Nkx2.1 relatively.CONCLUSIONS1.Exposure of nickel smelting environment would phosphorylate Smad2,and activate TGF-β/Smad signaling pathway,alter the modification of histones,which could recur and up-regulate the expression of embryo lung development biomarker Nkx2.1,increase the lung cancer risk finally.2.Exposure of nickel smelting environment could change the posttranscriptional modifications of histone,make the level of H3K4me3 increased and H3K27me3 decreased,and regulate the expression of NKx2.1.3.Education levels,monthly income per capita and behavior habits would have indirect effects on H3K27me3,pSmad2 and Nkx2.1,which lead to a different risk of lung cancer,but the influence is much lower than the exposure of nickel smelting environment.