PCB cause global DNA hypomethylation of human peripheral blood monocytes in vitro.

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.