INHIBITION OF CELL-CELL COMMUNICATION BY METHYLSULFONYL METABOLITES OF POLYCHLORINATED BIPHENYL CONGENERS IN RAT-LIVER EPITHELIAL IAR-20 CELLS

The effects of three polychlorinated biphenyl (PCB) congeners and thei r six methylsulfonyl (MeSO2)-metabolites on cell communication have be en investigated in the scrape-loading/dye-transfer assay in IAR 20 rat liver epithelial cells. The results demonstrated that at non-cytotoxi c concentrations 2,2',4',5-tetrachlorobiphenyl, 2,2',4',5,5'-pentachlo robiphenyl (2,2',4',5,5'-pentaCB), 2,2',4',5,5',6-hexachlorobiphenyl ( 2,2',4',5,5', 6-hexa-CB), and their 3- and 4-MeSO2 derivatives complet ely inhibited the cell communication within 1 h. 4-MeSO2-2,2',4'5,5'-p entaCB 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-MeS O2 derivatives of the PCB congeners tested inhibit gap junction interc ellular communication at about the same potency as their parental comp ounds. Since inhibition of cell communication is often observed after treatment with many tumor promoters, our findings suggest that the met abolites may also act as tumor promoters.