Expression of endogenous retrovirus-like sequences and cellular oncogenes during phenobarbital treatment and regeneration in rat liver.

The expression of two cellular oncogenes (c-myc and c-Ha-ras), the epidermal growth factor receptor gene, and two endogenous retrovirus-like sequences (rat leukemia virus and 30S) was examined in control (nonregenerating) rat livers and at various times after partial hepatectomy. One group of rats had been fed phenobarbital (0.05%) for 16 days prior to the partial hepatectomy. The feeding of phenobarbital (0.05%) itself led to a 65% decrease in the level of epidermal growth factor receptor RNA, but no major change in the level of c-myc, H-ras, rat leukemia virus, or 30S RNAs, in the control rat livers. There was a considerable increase (4- to 5-fold) in the level of c-myc transcripts, at 12 and 48 h after partial hepatectomy in the phenobarbital-treated rats, and at 12 and 24 h in the rats on the control diet. By 72 h, the level of c-myc transcripts returned to normal in both groups of rats. A slight increase (about 1.5-fold) in the level of c-H-ras transcripts was seen at 24 h, which returned to normal levels by 168 h, in the regenerating livers of both the phenobarbital-treated and control diet rats. The regenerating livers displayed a marked decrease (3- to 4-fold) in the level of epidermal growth factor receptor RNA in both the phenobarbital and control diet rats. A marked increase (5- to 6-fold) in the level of transcripts homologous to the endogenous rat leukemia virus-like sequence was seen at 24 h in all of the regenerating livers, but there was no significant change in the level of RNAs homologous to 30S. Thus, the proliferation of normal rat liver cells mimics some but not all of the changes in mRNA levels that we have previously described in rat liver tumors.