Detection of activated c-H-ras oncogene in hepatocellular carcinomas developing in transgenic mice harboring albumin promoter-regulated simian virus 40 gene.

Hepatocellular carcinomas (HCCs) developing in transgenic mice harboring an albumin promoter-regulated simian virus 40 (SV40) tumor antigen gene were analyzed for activating point mutations of the c-H-ras oncogene. Oligonucleotide hybridization studies utilizing enzymatically amplified DNA sequences of paraffin-embedded tumor tissues revealed that 10 out of 25 HCCs contained either an A-to-T or an A-to-G conversion at the second position of codon 61. Northern blot studies confirmed expression of SV40 gene mRNAs in the tumor tissues of both mutation-positive and mutation-negative HCCs. These findings in association with earlier results thus strongly suggest that mutational activation of cellular oncogene may play an important role in SV40-initiated multistage hepatocarcinogenesis in vivo.