多污染物统计模型在金属混合暴露与DNA氧化损伤关联分析中的应用

Application of mixture analysis methods in association between metals mixture exposure and DNA oxidative damage

目的:应用多污染物统计模型研究金属混合暴露与DNA氧化损伤的关联,探讨引起DNA氧化损伤效应的关键组分。方法:以山东某钢铁公司钢铁冶炼企业工人作为研究对象。采用电感耦合等离子体质谱法检测尿液中金属元素浓度。采用超高效液相色谱-串联质谱法检测尿中8-羟基脱氧鸟苷(8-OHdG)浓度。应用贝叶斯核机器回归(BKMR)、弹性网络回归和分位数g计算回归分析尿金属与尿8-OHdG的关联。结果:共纳入研究对象共768名,年龄(36.15±7.40)岁。BKMR、弹性网络回归、分位数g计算回归结果均显示,金属混合暴露与尿8-OHdG水平升高的关联有统计学意义。分位数g计算回归结果显示,金属混合物水平每增加25%,尿8-OHdG水平增加77.60%。弹性网络分析显示,暴露风险得分每增加25%,尿8-OHdG水平增加26%。BKMR的单变量暴露效应分析显示,尿硒、锌、镍与尿8-OHdG水平存在正相关。结论:金属混合暴露引起DNA氧化损伤水平升高,其中硒、锌和镍的作用更加明显。

Objectives To study the association between metals mixture exposure and DNA oxidative damage using mixture analysis methods,and to explore the most significant exposure factors that cause DNA oxidative damage.Methods Workers from steel enterprises were recruited in Shandong Province.Urinary metals were measured by using the inductively coupled plasma mass spectrometry method.The level of urinary 8-hydroxy-2′-deoxyguanosine(8-OHdG)was determined by using the ultra-high performance liquid chromatography-mass spectrometry method.Bayesian kernel machine regression(BKMR),elastic net regression and quantile g-computation regression were used to analyze the association between urinary metals and urinary 8-OHdG.Results A total of 768 subjects aged(36.15±7.40)years old were included in the study.BKMR,elastic net regression and quantile g-computation all revealed an overall positive association between the mixture concentration and increased urinary 8-OHdG.The quantile g-computation results showed that with a 25%increase in metal mixtures,the urinary 8-OHdG level increased by 77.60%.The elastic net regression showed that with a 25%increase in exposure risk score,the urinary 8-OHdG level increased by 26%.The BKMR summarized the contribution of individual exposures to the response,and selenium,zinc,and nickel were significant contributors to the urinary 8-OHdG elevation.Conclusion Exposure to mixed metals causes elevated levels of DNA oxidative damage,and selenium,zinc,and nickel are significant exposure factors.