Cellular analysis of c-Ha- ras gene expression in rat liver after CCl4 administration

Abstract

Expression of the c-Ha-ras proto-oncogene is specifically enhanced during liver regeneration, in parallel with increased DNA replication, which suggests that c-Ha-ras may play a role in the control of regeneration. In this study, an in situ hybridization technique was applied for analysis of expression of the c-Ha-ras gene at the cellular level during liver regeneration induced by CCl₄ administration. The in situ hybridization was compared with the observation for the p21^c-Ha-ras protein, the corresponding protein of the c-Ha-ras gene, by immunohistochemistry. In normal rat liver, a few hepatocytes expressed the mRNAs and the corresponding proteins without any preferential localization. Zonal heterogeneity of c-Ha-ras gene expression first became evident at 12 hr after CCl₄ administration, a higher number of gene products being detected in the pericentral zone than in the periportal zone. This heterogeneity became maximal at 24 hr after CCl₄ administration. Zonal heterogeneity in the level of the p21^c-Ha-ras protein paralleled that in the level of gene expression. Furthermore, both hepatocytes and nonparenchymal cells participated in expression of the c-Ha-ras gene during liver regeneration.