Prevention of the down-regulation of gap junctional intercellular communication by green tea in the liver of mice fed pentachlorophenol.
Much evidence has been documented supporting the hypothesis that the down-regulation of gap junctional intercellular communication (GJIC) is a cellular event underlying the tumor promotion process and that treatment to prevent the down-regulation or to up-regulate GJIC is important in preventing tumor promotion. We explored the potential preventive effects of green tea against the promoting action of pentachlorophenol (PCP) in mouse hepatocarcinogenesis, examining whether drinking green tea prevents the down-regulation of GJIC inhibition in the liver caused by tumorigenic doses of PCP. We used a modified in vivo GJIC assay, the incision loading/dye transfer method. Male B6C3F1 mice were given a green tea infusion for 1 week and then PCP was fed at a dose of 300 or 600 p.p.m. in the diet for the following 2 weeks, along with green tea treatment. A dose-related inhibition of GJIC in the hepatocytes was evident in the mice treated with PCP alone that was associated with a reduction in connexin32 (Cx32) plaques in the plasma membrane and an increase in the cell proliferation index. Drinking green tea significantly protected mice against GJIC inhibition, the reduction in Cx32 and the elevation of the labeling index. These findings suggest that green tea might act as an anti-promoter against PCP-induced mouse hepatocarcinogenesis via its ability to prevent down-regulation of GJIC.
Sai
K
K
Division of Cellular and Molecular Toxicology and Division of Risk Assessment, National Institute of Health Sciences, 1-18-1 Kamiyohga, Setagayaku, Tokyo 158-8501, Japan.
Kanno
J
J
Hasegawa
R
R
Trosko
J E
JE
Inoue
T
T
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002273:Carcinogens / Q000633:toxicity*; D002450:Cell Communication / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D017630:Connexins / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005456:Fluorescent Dyes; D017629:Gap Junctions / Q000187:drug effects*; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010416:Pentachlorophenol / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008517:Phytotherapy; D013662:Tea / Q000627:therapeutic use*; D000097002:Gap Junction beta-1 Protein
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D017630:Connexins; D005456:Fluorescent Dyes; D010416:Pentachlorophenol; D013662:Tea; D000097002:Gap Junction beta-1 Protein