Wen Weihua, Li Ying, Cheng Huirong, Wang Pan, Tang Yanhong
Yunnan Provincial Center for Disease Control and Prevention, Kunming 650022, China.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2015 Dec;33(12):891-3. doi: 10.3760/cma.j.issn.1001-9391.2015.12.003.
To investigate the changes in mRNA expression of p53 and related downstream genes in peripheral blood lymphocytes in workers occupationally exposed to arsenic as well as its influencing factors, and to analyze the mechanism of genetic toxicity of arsenic.
With cluster random sampling, 79 workers from an arsenic smelting plant were selected as exposure group, and another 24 people without occupational exposure to arsenic were selected as control group. The relative mRNA expression of p53 and related downstream genes in the peripheral blood lymphocytes of the two groups was determined by quantitative realtime PCR. The levels of inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) in urine were determined by hydride generation-atomic absorption spectrometry.
The exposure group had significantly higher levels of iAs, MMA, and DMA than the control group (P<0.01); the exposure group had significantly higher relative mRNA expression (2(-ΔΔCt)) of p53 and four related downstream genes in peripheral blood lymphocytes than the control group (P<0.05); the relative mRNA expression of p53 and related downstream genes was positively correlated with each other (P<0.01), with a correlation coefficient greater than 0.4; the levels of arsenic compounds in urine were positively correlated with the relative mRNA expression of p53 and some of its downstream genes (P<0.05).
The changes in mRNA expression of p53 and related downstream genes are closely related to the metabolic transformation of inorganic arsenic in workers occupationally exposed to arsenic, and it also plays an important role in genetic toxicity and carcinogenic effect in people exposed to arsenic.
探讨职业接触砷工人外周血淋巴细胞中p53及其相关下游基因mRNA表达变化及其影响因素,分析砷的遗传毒性机制。
采用整群随机抽样法,选取某砷冶炼厂79名工人作为暴露组,另选取24名无职业砷接触史的人员作为对照组。采用定量实时荧光定量PCR法检测两组外周血淋巴细胞中p53及其相关下游基因的相对mRNA表达。采用氢化物发生-原子吸收光谱法测定尿中无机砷(iAs)、一甲基砷酸(MMA)和二甲基砷酸(DMA)水平。
暴露组尿中iAs、MMA和DMA水平均显著高于对照组(P<0.01);暴露组外周血淋巴细胞中p53及其4个相关下游基因的相对mRNA表达(2(-ΔΔCt))均显著高于对照组(P<0.05);p53及其相关下游基因的相对mRNA表达之间呈正相关(P<0.01),相关系数大于0.4;尿中砷化合物水平与p53及其部分下游基因的相对mRNA表达呈正相关(P<0.05)。
职业接触砷工人p53及其相关下游基因mRNA表达变化与无机砷的代谢转化密切相关,在砷暴露人群的遗传毒性和致癌作用中也起重要作用。