镍冶炼工人尿镍水平与<i>p15</i>、<i>p16</i>启动子甲基化的关系

杨瑾; 王志武; 郭庆峰; 孙建娅

镍冶炼工人尿镍水平与p15、p16启动子甲基化的关系

Correlation between Urinary Nickel and Methylation of p15 and p16 in Blood DNA of Workers Exposed to Nickel

摘要

摘要:
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、4.52 μg/L,与水处理工人的尿镍浓度中位数(1.78 μg/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(P0.023);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(P0.082)。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。

Abstract:
Objective To study the correlation between urinary nickel and methylation of anti-oncogene p15 and p16 in blood DNA of workers exposed to nickel.

Methods Totally 165 nickel exposed workers and 65 water treatment workers without occupational nickel exposure were recruited in this study. The levels of urinary nickel were determined by dimethylglyoxime spectrophotometry. Methylation specific polymerase chain reaction (MSP) was used to detect the methylation of p15 and p16 in blood DNA.

Results The median concentrations of urinary nickel in steel refining workers (5.34 μg/L), slaggers (4.59 μg/L) and mill men (4.52 μg/L) were significantly higher than that in the controls (1.78 μg/L) (P<0.01). The methylation rate of p15 in the exposed group (24.55%) was significantly higher than that in the control group (11.94%) (P0.023). However, no significant difference in the methylation rate of p16 between the exposed group (21.82%) and the control group (11.94%) was found (P0.082). The multivariate logistic analysis showed that workers bearing higher urinary nickel levels were at higher risks of developing p15 methylation (OR=1.47, P0.024).

Conclusion The level of urinary nickel is significantly correlated with the methylation of p15 in blood DNA.

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