title: Hepatic gap junctions in the hepatocarcinogen-resistant DRH rat.
abstract: Although the gap junction or connexin (Cx) is considered to be a tumor-suppressor, it is also required for tumor promotion. Therefore, we examined hepatic gap junctions in hepatocarcinogen-resistant (DRH) rats. Specifically, we investigated gap junction structure and Cx32 expression during normal conditions and in response to a hepatocarcinogen, 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). On a basal diet without 3'-MeDAB, hepatic gap junctions and Cx32 protein expression were greater in DRH rats than in control Donryu rats, as evidenced by morphometry, immunohistochemistry and immunoblotting. On a diet containing 3'-MeDAB, gap junctions and expressed Cx32 were increased significantly in Donryu rats, but not in DRH rats. In this condition, Donryu rats lost weight but DRH rats increased relative liver weight. After 3'-MeDAB treatment, cathepsin D expression in hepatocytes was significantly increased only in Donryu rats, indicating that DRH rats were less susceptible to 3'-MeDAB. The abundance of mitogen-activated protein kinase, some constituent of which might be associated with the degree of Cx protein phosphorylation, was reduced to a greater extent in Donryu than in DRH rats after 3'-MeDAB treatment. The resistance of DRH rats to carcinogenesis may be due partially to their stabilized gap junctions, which could coordinate metabolic coupling to evade 3'-MeDAB toxicity.
authors.affiliation: Laboratory of Cell Biology, College of Nutrition, Koshien University, 10-1 Momijigaoka, Takarazuka Hyogo 665-0006, Japan. gotow@koshien.ac.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Gotow
authors.forename: Motoko
authors.initials: M
authors.lastname: Shiozaki
authors.forename: Taneaki
authors.initials: T
authors.lastname: Higashi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shibata
authors.forename: Eiki
authors.initials: E
authors.lastname: Kominami
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Uchiyama
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002402:Cathepsin D / Q000378:metabolism; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D004351:Drug Resistance; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008099:Liver / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051381:Rats; D000097002:Gap Junction beta-1 Protein
chemical_list: D002273:Carcinogens; D002402:Cathepsin D; D017630:Connexins; D020928:Mitogen-Activated Protein Kinases; D000097002:Gap Junction beta-1 Protein