title: Inhibitory effect of pentachlorophenol on gap junctional intercellular communication in rat liver epithelial cells in vitro.
abstract: To understand the initiating/promoting actions of pentachlorophenol (PCP), a non-mutagenic hepatocarcinogen, and its metabolite, tetrachlorohydroquinone (TCHQ), we investigated the effects of each chemical on gap junctional intercellular communication (GJIC) in rat liver epithelial cells (WB cells) by the scrape-loading and dye transfer method. After treatment with PCP, the GJIC was initially inhibited at 4 h but was restored in 6-8 h, followed by a second phase of inhibition between 16 and 24 h. Both the first and second inhibitions were concentration-dependent and were restored by 2-4 h after removal of PCP. The phosphorylation state of connexin 43 (CX43) and its localization on the plasma membrane were unchanged up to 24 h after treatment; however, this was accompanied by a decrease in the CX43 protein level. No inhibitory effect was apparent on the GJIC of cells treated with TCHQ. These results suggest that PCP may play a critical role of promoting activity via non-mutagenic mechanisms.
authors.affiliation: Division of Cellular and Molecular Toxicology, National Institute of Health Sciences, Tokyo, Japan. sai@nihs.go.jp
authors.forename: K
authors.initials: K
authors.lastname: Sai
authors.forename: B L
authors.initials: BL
authors.lastname: Upham
authors.forename: K S
authors.initials: KS
authors.lastname: Kang
authors.forename: R
authors.initials: R
authors.lastname: Hasegawa
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.forename: J E
authors.initials: JE
authors.lastname: Trosko
mesh_terms: D000818:Animals; D002460:Cell Line; D018031:Connexin 43 / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects*; D006873:Hydroquinones / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010416:Pentachlorophenol / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors
chemical_list: D018031:Connexin 43; D006873:Hydroquinones; C044578:2,3,5,6-tetrachlorohydroquinone; D010416:Pentachlorophenol