Inhibition of cell-cell communication by methylsulfonyl metabolites of polychlorinated biphenyl congeners in rat liver epithelial IAR 20 cells

Abstract

The effects of three polychlorinated biphenyl (PCB) congeners and their six methylsulfonyl (MeSO₂)-metabolites on cell communication have been investigated in the scrape-loading/dye-transfer assay in IAR 20 rat liver epithelial cells. The results demonstrated that at non-cytotoxic concentrations 2,2′,4′,5-tetrachlorobiphenyl, 2,2′,4′,5,5′-pentachlorobiphenyl (2,2′,4′,5,5′-pentaCB), 2,2′,4′,5,5′,6-hexachlorobiphenyl (2,2′,4′,5,5′, 6-hexaCB), and their 3- and 4-MeSO₂ derivatives completely inhibited the cell communication within 1 h. 4-MeSO₂-2,2′,4′,5,5′-pentaCB and 4-MeSO₂-2,2′,4′,5, 5′,6-hexaCB appeared to inhibit the cell communication at slightly lower concentration than their parental PCB congeners and 3-MeSO₂ derivatives. The results show that 3- and 4-MeSO₂ derivatives of the PCB congeners tested inhibit gap junction intercellular communication at about the same potency as their parental compounds. Since inhibition of cell communication is often observed after treatment with many tumor promoters, our findings suggest that the metabolites may also act as tumor promoters.