Inhibitory effect of pentachlorophenol on gap junctional intercellular communication in rat liver epithelial cells in vitro.
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.
Sai
K
K
Division of Cellular and Molecular Toxicology, National Institute of Health Sciences, Tokyo, Japan. sai@nihs.go.jp
Upham
B L
BL
Kang
K S
KS
Hasegawa
R
R
Inoue
T
T
Trosko
J E
JE
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
D018031:Connexin 43; D006873:Hydroquinones; C044578:2,3,5,6-tetrachlorohydroquinone; D010416:Pentachlorophenol