摘要目的: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。

abstractsObjectives: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.