中文摘要：

以体外培养人Bel-7402肝癌细胞为模型,研究铅的3种常见化合物氯化铅（Pb Cl2）、乙酸铅（Pb（CH3COO）2）、硝酸铅（Pb（NO3）2）的细胞毒性和去甲基化表观遗传毒性。应用MTS方法检测细胞的存活率,以前期研究建立的评价方法评价铅化合物的去甲基化表观遗传毒性。结果显示,Pb Cl2、Pb（CH3COO）2、Pb（NO3）2均会抑制Bel-7402细胞的增值,计算求得Pb Cl2、Pb（CH3COO）2、Pb（NO3）2相应的50%细胞存活浓度（IC50）值分别为2 524μmol·L^（-1）、1 977μmol·L^（-1）、1 899μmol·L^（-1）;80%细胞存活浓度（IC80）值分别为264μmol·L^（-1）、221μmol·L^（-1）、281μmol·L^（-1）,通过对3种染毒物不同染毒浓度的细胞存活率进行随机区组设计的方差分析显示3种化合物间的差异无统计学意义（F=0.11;P=0.897）。去甲基化表观遗传毒性检测结果显示,Pb Cl2、Pb（CH3COO）2、Pb（NO3）2均可观察到明显的去甲基化表观遗传毒性,其相对于5-氮杂-2-脱氧胞苷（5-Aza-Cd R）的去甲基化表观遗传毒性当量分别为2.82E-03、1.50E-03、5.09E-04,三者间也无显著性差异。结果表明,铅化合物会使Bel-7402细胞的细胞存活率和转染进细胞的质粒上增强型绿色荧光蛋白基因启动子的DNA甲基化水平下降。

英文摘要：

Human liver cancer Bel-7402 cells were used to estimate the cell toxicity and demethylation toxicity of 3lead compounds including lead chloride（Pb Cl2）, lead acetate（Pb（CH3COO）2） and lead nitrate（Pb（NO3）2）. Cell viability was estimated firstly by MTS assay, and the demethylation toxicity of lead compounds was quantified by the method established and reported in earlier study. The results showed Pb Cl2, Pb（CH3COO）2and Pb（NO3）2all significantly inhibited the Bel-7402 cell proliferation and the IC50 values were 2 524 μmol·L^（-1）, 1 977 μmol·L^（-1）, 2 524 μmol·L^（-1）; the IC8 0values were 264 μmol·L^（-1）, 221 μmol·L^（-1）, 281 μmol·L^（-1）. There was no significant difference of cell viability among 3 cell groups treated with different lead compounds（F = 0.11; P = 0.897）. However significant epigenetic demethylation toxicity was observed for 3 compounds and their demethylation toxicity equivalency was 2.82E-03, 1.50E-03 and 5.09E-04 folds of 5-AZA-Cd R, respectively. No significant difference was observed among their demethylation toxicity equivalency. The study revealed that lead compounds can inhibit Bel-7402 cell proliferation and induce obvious demethylation effect on DNA methylation levels at promoter region of EGFP gene.