CLOFIBRATE-INDUCED NEOPLASTIC DEVELOPMENT IN THE RAT-LIVER IS ASSOCIATED WITH DECREASED CONNEXIN-32 EXPRESSION BUT NOT WITH A COORDINATED SHIFT IN EXPRESSION OF MARKER ENZYMES

Altered enzyme phenotype and expression of connexin 32 (Cx32), a gap j unction protein were studied during the development of rat liver tumor s induced by the non-genotoxic carcinogen, clofibrate. (1) In contrast to previous findings for nitrosamine-induced lesions. preneoplastic e nzyme-altered foci (EAF) and neoplastic nodules (NN) lacked any clear association with degree of altered enzyme expression because of an alm ost complete negativity for GST-P and GGT. (2) Immunohistochemically d emonstrated Cx32 spots on the hepatocyte membranes showed a clear decr ease in clofibrate-induced lesions. (3) Naturally occurring EAF demons trating GST-P and/or GGT positivity did not show a significant decreas e of Cx32 counts suggesting a reversible nature. Therefore, the Cx32 d ecrease appears closely linked to progression of hepatocarcinogenesis irrespective of the enzyme phenotype of neoplastic focal lesions and t he carcinogens used for their induction.