We have recently reported significant associations between exposure to polychlorinated biphenyls (PCB) and alterations on genome-wide methylation of leukocyte DNA of healthy volunteers and provided evidence in support of an etiological link between the observed CpG methylation variations and chronic lymphocytic leukemia. The present study aimed to elucidate the effects of PCB in human lymphocytes’ methylome in vitro. Therefore, U937 cells and human peripheral blood monocytes (PBMC) were exposed in vitro to the dioxin-like PCB-118, the non-dioxin-like PCB-153, and hexachlorobenzene (HCB) and thorough cytotoxicity, genotoxicity and global CpG methylation analyses were performed. All compounds currently tested did not show any consistent significant genotoxicity at all exposure periods and concentrations used. On the contrary, extensive dose-dependent hypomethylation was observed, even at low concentrations, in stimulated PBMC treated with PCB-118 and PCB-153 as well as a small but statistically significant hypomethylation in HCB-treated stimulated cells.

我们最近报道多氯联苯（PCB）和变更曝光之间显著关联于健康志愿者的白细胞DNA的全基因组甲基化和支持所观察到的甲基化变型和慢性淋巴细胞性白血病之间的病因链路提供了证据。旨在本研究阐明人淋巴细胞甲基化PCB的影响在体外。因此，U937细胞和人外周血单核细胞（PBMC）暴露在体外到二恶英类PCB-118，非类二恶英PCB-153，和六氯苯（HCB）和彻底的细胞毒性，遗传毒性和全球CpG甲基化分析进行。目前测试的所有化合物并没有表现出在使用的所有的暴露时间和浓度任何一致显著遗传毒性。相反，即使在低浓度下，在用 PCB-118 和 PCB-153 处理的刺激 PBMC 中也观察到了广泛的剂量依赖性低甲基化，并且在 HCB 处理的刺激细胞中观察到了少量但具有统计学意义的低甲基化。