beta-catenin (Ctnnb1) gene mutations in diethylnitrosamine (DEN)-induced liver tumors in male F344 rats

Alterations in multiple phosphorylation sites on exon 3 of the beta-catenin gene have recently been implicated in hepatocarcinogenesis in humans as we ll as mice. To identify genetic alterations which could be involved in the chemical-induced hepatocarcinogenesis of rats, we analyzed the status of th e sites in the beta-catenin gene (Ctnnb1) of liver neoplasms induced by die thylnitrosamine (DEN) in male F344 rats, using the polymerase chain reactio n-single strand conformation polymorphism method. In the present investigat ion, we examined 35 hepatocellular neoplasms (28 adenomas and 7 carcinomas) for the expression of mutations in the region of the beta-catenin gene, Po int mutation at codon 32, 35, 37 or 41, which has been reported in human an d mouse liver cell carcinomas and/or other cancers, was recognized in eleve n (31%) out of 35 lesions (8 adenomas and 3 carcinomas). Our results indica te that Ctnnb1 mutations may contribute to hepatocarcinogenesis in rats. Ou r finding that Ctnnb1 mutation was present in adenomas as well as carcinoma s also suggests that the mutation is a relatively early event in DEN-induce d hepatocarcinogenesis in rats.