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 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.
Kato
Y
Y
School of Pharmaceutical Sciences, University of Shizuoka, Yada, Japan.
Kenne
K
K
Haraguchi
K
K
Masuda
Y
Y
Kimura
R
R
Wärngård
L
L
D000476:Alkanesulfonates / Q000633:toxicity*; D000818:Animals; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D017629:Gap Junctions / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000502:physiology; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats
D000476:Alkanesulfonates; D011078:Polychlorinated Biphenyls