Abstract

Connexin genes have been shown to restore normal cell growth when transfected into certain tumorigenic cells and thus are considered to form a family of tumor suppressor genes. In this study, we have analyzed mutations of the connexin 37 (Cx37) gene in rat hepatic angiosarcomas induced by vinyl chloride. A total of 25 rat liver tumors (22 hepatic angiosarcomas and 3 hepatocellular carcinomas) were analyzed by PCR-single-strand conformation polymorphism analysis and DNA sequencing. Four mutations were detected in three tumors: ( a ) one GGG Gly to GAG Glu mutation at codon 168; and ( b ) three silent mutations, CGA Arg to CGC Arg , at codon 166. In addition, we found that codon 88 is polymorphic (GAG Glu to GAA Glu ). Cx37 proteins are detectable in endothelial cells of normal liver by immunohistochemical analysis, but none of the angiosarcomas showed Cx37 -positive spots. These results suggest that Cx37 -mediated gap junctional intercellular communication may be disturbed in most of these angiosarcomas, but mutation of the Cx37 gene is rare. 1 To whom requests for reprints should be addressed.