| Objective1.To explore the dose-response relationship between occupational polycyclic aromatic hydrocarbons(PAHs)internal exposure and peripheral blood leukocyte mitochondrial damage in coke oven plants workers,and to estimate the benchmark dose of PAHs-exposure induced mitochondrial damage.2.To explore the effect of miRNAs genes polymorphism on mitochondrial DNA copy number(mtDNAcn)in PAHs-exposure population.Subjects and Methods1.Subjects:Exposure group was from 544 workers exposed to coke oven emissions for more than one year in coke plant of Henan.238 controls were healthy population without the exposure of occupational PAHs and other poison in the same period.After informed consent,the subjects were investigated by questionnaire and collected by peripheral blood and end-of-class urine biological samples.2.Methods:The ultrahigh performance liquid chromatography was used to detect concentration of PAHs urinary metabolites 1-hydroxypyrene,1-hydroxynaphthalene,2-hydroxynaphthalene and 3-hydroxyphenanthrene.The real-time fluorescence quantitative polymerase chain reaction was used to determine mtDNAcn of peripheral blood leukocytes.The matrix-assisted laser desorption ionization time-of-flight mass spectrometry was used to detect the miRNAs gene polymorphisms.3.Statistical analysis:Data statistical analyses used SPSS 21.0 software(SPSS Inc.,Chicago,IL,USA).The independent sample t tests were used to analyze differences in continuous demographic data.The differences and trends between qualitative data groups were analyzed by chi-square test.The Mann-Whitney U test was used to analyze the difference of quantitative data between exposure group,control group and sub-groups.The covariance was used to analyze the effects of sex,age,smoking,alcohol consumption,body mass index(BMI),working duration and miRNAs polymorphism on mtDNAcn.The multivariate linear regression model was used to analyze the influencing factors of mtDNAcn.Benchmark Dose Software 2.7.0.4 Version(U.S.EPA)was used for calculating benchmark dose of PAHs urinary metabolites.Results1.The mtDNAcn of peripheral blood leukocyte in exposed group(0.60±0.29)was significantly lower than that in control group(1.03±0.31),(t=18.931,P<0.001).The concentrations of 1-hydroxypyrene,1-hydroxynaphthalene,2-hydroxynaphthalene and 3-hydroxyphenanthrene in the exposed group were significantly higher than those in the control group(P<0.001).2.The significant dose-response relationship between 1-hydroxypyrene and 3-hydroxyphenanthrene with mitochondrial DNA damage.The benchmark dose lower confidence limit(BMDL)of 1-hydroxypyrene were 0.045,0.004,and 0.058pg/?g creatinine in the total,male,and female population,respectively.The BMDL of 3-hydroxyphenanthrene were 5.142,6.099,and 2.807pg/?g creatinine in the total,male,and female population,respectively.3.Covariance analysis showed that the mtDNAcn in AA+AG for miR-210 rs 11246190 locus was significantly lower than that of GG genotype in the exposure group(P<0.001).The individuals of CC genotypes in miR-210 rs7395206 locus had lower mtDNAcn than those of the CT+TT genotype in the control group(P=0.028).The individuals carrying GG genotypes had lower mtDNAcn than those of AG+AA genotypes for miR-126 rs2297538 locus in the exposure group(P=0.036).The multiple linear regression models found that mtDNAcn decreased influencing factors included:PAHs-exposure,male,and miR-210 rs 11246190 locus carrying AA or AG genotypes.Conclusions1.There is a dose-response relationship between PAHs urinary metabolites 1-hydroxypyrene,3-hydroxyphenanthrene and mitochondrial DNA damage in peripheral blood leukocytes.The BMDL of 1-hydroxypyrene and 3-hydroxyphenanthrene initially explored in this study can provide a reference for the country to establish occupational exposure biological limits.2.PAHs-exposure,sex,and miR-210 rs 11246190 locus polymorphisms are associated with mtDNAcn of peripheral blood leukocytes in PAHs-exposure population. |
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