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目的探讨苯接触工人外周血中淋巴细胞p53基因mRNA的表达,分析p53基因表达与苯接触量以及p53-Mdm2-p14ARF通路基因多态的关系。方法选取职业苯接触工龄≥1a的77名工人为接触组,37名无职业性苯及其他毒物接触史的本地志愿者为对照组,采用实时定量PCR嵌合荧光法检测其外周血中淋巴细胞p53基因mRNA表达量。同时采用限制性长度多态检测法对接触组工人p53-Mdm2-p14ARF通路中8个基因多态进行检测。结果接触组和对照组p53基因mRNA相对表达量(2-△Ct×103)的中位数及上、下四分位数分别为1.85(0.57,4.04)和15.41(9.29,25.56),经稳健线性回归分析排除年龄、性别等因素的影响,两组表达量差异有统计学意义(P<0.01)。根据苯累计接触剂量将接触组分为低、中、高苯累计接触组,各组p53基因表达水平均明显低于对照组(P<0.01),其相对表达量随累计接触剂量的增加而降低(P<0.01)。携带p14ARF基因rs3731245多态突变型个体p53基因mRNA表达水平则明显低于野生纯合型(P<0.05)。结论苯接触可引起机体外周血中p53基因mRNA表达量降低。
OBJECTIVE: To investigate the expression of p53 gene mRNA in peripheral lymphocytes of benzene exposed workers, and to analyze the relationship between p53 gene expression and benzene exposure and p53-Mdm2-p14ARF pathway gene polymorphism. Methods Totally 77 local workers who were exposed to occupational benzene for more than one year were selected as the control group by local volunteers who were exposed to occupational benzene and other toxicants for the exposure group. Real-time quantitative PCR was used to detect the peripheral blood lymphocytes p53 gene mRNA expression. At the same time, 8 polymorphisms of p53-Mdm2-p14ARF pathway in contact workers were detected by restriction-length polymorphism (PCR-RFLP). Results The median and upper and lower quartile of p53 gene mRNA expression (2 △ △ Ct × 103) were 1.85 (0.57, 4.04) and 15.41 (9.29, 25.56) respectively in contact group and control group, Linear regression analysis excluded age, gender and other factors, the difference between the two groups was statistically significant (P <0.01). According to the cumulative exposure dose of benzene, the contact components were divided into low, medium and high benzene cumulative exposure groups, the expression levels of p53 gene in each group were significantly lower than those in the control group (P <0.01), and their relative expression levels were decreased with the increase of cumulative exposure dose (P <0.01). The p53 gene mRNA of rs3731245 polymorphic mutant carrying p14ARF gene was significantly lower than wild homozygote (P <0.05). Conclusion Benzene exposure can cause the expression of p53 gene mRNA in the peripheral blood of the rats decreased.