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Connexin 37 Mutations in Rat Hepatic Angiosarcomas Induced by Vinyl Chloride

Units of Multistage Carcinogenesis [T. S., Y. O., H. Y.] and Environmental Carcinogenesis [A. B.], International Agency for Research on Cancer, 150, cours Albert-Thomas, F-69372, Lyon 08, France

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.

Received 9/10/96. Accepted 12/18/96.

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