title: Clofibrate-induced neoplastic development in the rat liver is associated with decreased connexin 32 expression but not with a co-ordinated shift in expression of marker enzymes.
abstract: Altered enzyme phenotype and expression of connexin 32 (Cx32), a gap junction protein were studied during the development of rat liver tumors induced by the non-genotoxic carcinogen, clofibrate. (1) In contrast to previous findings for nitrosamine-induced lesions, preneoplastic enzyme-altered foci (EAF) and neoplastic nodules (NN) lacked any clear association with degree of altered enzyme expression because of an almost complete negativity for GST-P and GGT. (2) Immunohistochemically demonstrated Cx32 spots on the hepatocyte membranes showed a clear decrease in clofibrate-induced lesions. (3) Naturally occurring EAF demonstrating GST-P and/or GGT positivity did not show a significant decrease of Cx32 counts suggesting a reversible nature. Therefore, the Cx32 decrease appears closely linked to progression of hepatocarcinogenesis irrespective of the enzyme phenotype of neoplastic focal lesions and the carcinogens used for their induction.
authors.affiliation: Chemotherapy Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tsuda
authors.forename: M
authors.initials: M
authors.lastname: Asamoto
authors.forename: H
authors.initials: H
authors.lastname: Baba-Toriyama
authors.forename: Y
authors.initials: Y
authors.lastname: Iwahori
authors.forename: T
authors.initials: T
authors.lastname: Hori
authors.forename: D J
authors.initials: DJ
authors.lastname: Kim
authors.forename: T
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: M
authors.initials: M
authors.lastname: Mutai
authors.forename: H
authors.initials: H
authors.lastname: Yamasaki
mesh_terms: D000818:Animals; D002994:Clofibrate / Q000633:toxicity*; D017630:Connexins / Q000032:analysis*; D017629:Gap Junctions / Q000502:physiology; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D000097002:Gap Junction beta-1 Protein
chemical_list: D002994:Clofibrate; D017630:Connexins; D000097002:Gap Junction beta-1 Protein