Effects on intercellular communication in human keratinocytes and liver-derived cells of polychlorinated biphenyl congeners with differing in vivo promotion activities

Carcinogenesis
S H SwierengaD J Fitzgerald

Abstract

Several purified polychlorinated biphenyl (PCB) congeners with differing toxicity/tumor promotional activities in rat liver in vivo were tested for their effects on gap-junctional intercellular communication (GJIC) in cell strains and lines derived from human liver and skin. This in vitro assay is being developed to detect various classes of tumor promoters. The 3-methylcholanthrene (MCA)-type cytochrome P450 inducer and hepatotoxic promoter 3,3',4,4'-tetrachlorobiphenyl was inactive in this assay for all of the cells tested, suggesting this promoter acts by other mechanisms. The phenobarbital-like enzyme inducer and less toxic promoter 2,2',4,4',5,5'-hexachlorobiphenyl inhibited GJIC in both liver and skin cells, whereas the 2,2',5,5'-tetrachlorobiphenyl congener, which does not act as a promoter in rat liver, inhibited GJIC only in the skin cell types and in one of the liver cell strains thought to be of bile duct origin. 2,3,4,4',5-Pentachlorobiphenyl, a mixed (phenobarbital plus MCA) inducer of cytochrome P450, inhibited GJIC in both liver and skin cells, suggesting that it may be a promoter in vivo. The results suggest that GJIC inhibition is a property of PCB congeners with phenobarbital-like enzyme induction capabilities...Continue Reading

Citations

Feb 4, 2005·Archives of Toxicology·Edgar Rivedal, Gisela Witz
Jan 1, 1991·Toxicology in Vitro : an International Journal Published in Association with BIBRA·S H SwierengaM Goldberg
Apr 15, 2003·Toxicology and Applied Pharmacology·Jürgen BorlakElmar Richter
Oct 4, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Pavlína SimeckováMiroslav Machala
Dec 1, 1991·Pharmacology & Toxicology·H HemmingU G Ahlborg
Nov 26, 2009·Chemico-biological Interactions·Edgar RivedalEdward Leithe
Jan 24, 2006·Toxicology Letters·Susanne KunzHans-Joachim Schmitz
Nov 5, 2003·Critical Reviews in Toxicology·Robert GoldenJack Mandel
Aug 28, 2021·International Journal of Molecular Sciences·Iva SovadinováPavel Babica

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