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[目的]探讨镍冶炼工人尿镍水平与抑癌基因p15、p16启动子甲基化的关系。[方法]采用丁二酮肟分光光度法测定不锈钢冶炼厂165名镍作业工人(镍接触组)和67名水处理工人(对照组)尿镍浓度,并采用甲基化特异性聚合酶链反应(methylation specific polymerase chain reaction,MSP)检测抑癌基因p15、p16启动子的甲基化状态。[结果]炼钢工、钢渣处理工、轧钢工的尿镍浓度中位数分别为5.34、4.59、4.52μg/L,与水处理工人的尿镍浓度中位数(1.78μg/L)比较,差异均有统计学意义(P<0.01)。镍接触组的p15基因启动子甲基化检出率为25.45%,与对照组甲基化检出率(11.94%)相比,差异有统计学意义(P=0.023);而镍接触组p16基因启动子甲基化检出率(21.82%)与对照组(11.94%)相比,差异无统计学意义(P=0.082)。多元logistic回归分析显示,尿镍浓度高个体的p15甲基化发生可能性为尿镍浓度低个体的1.47倍。[结论]尿镍浓度与p15启动子甲基化的发生有密切关系。
[Objective] To investigate the relationship between urine nickel level and tumor suppressor gene p15, p16 promoter methylation in nickel smelters. [Method] Urinary nickel concentration was measured by dimethylglyoxime spectrophotometry in 165 nickel workers (nickel contact group) and 67 water treatment workers (control group) in stainless steel smelter. The methylation specific polymerase chain reaction methylation specific polymerase chain reaction (MSP) was used to detect the methylation status of the tumor suppressor genes p15 and p16. [Result] The median of urinary nickel concentrations of steel-making workers, steel-slag workers and steel-rolling workers were 5.34, 4.59 and 4.52 μg / L, respectively. Compared with the median of urine nickel concentration of water treatment workers (1.78 μg / L) The differences were statistically significant (P <0.01). The methylation detection rate of p15 gene in nickel exposure group was 25.45%, which was significantly different from that in control group (11.94%) (P = 0.023), while nickel exposure group p16 The detection rate of gene promoter methylation (21.82%) was not significantly different from that of control group (11.94%) (P = 0.082). Multivariate logistic regression analysis showed that the probability of p15 methylation in individuals with high urinary nickel concentrations was 1.47 times higher than that in individuals with low urinary nickel concentrations. [Conclusion] Urinary nickel concentration is closely related to the occurrence of p15 promoter methylation.