Expression Pattern of the Genes for Different Members of the Heat‐Shock Protein 70 Family, Ornithine Decarboxylase, and c‐Ha‐ras During the Early Stages of Hepatocarcinogenesis

Northern blot analysis with specific probes indicates that, in the liver of normothermic rats under the carcinogenic regimen of Solt and Farber (Nature 263:701, 1976), diethylnitrosamine (DEN), 2-acetylaminofluorene (AAF), and partial hepatectomy (PH), either alone or in combination, do not induce the expression of the heat-shock protein 70 (hsp70) gene family. On the contrary, the inducibility of hsp70 mRNAs in the liver of heat-shocked animals is maintained throughout the treatment, as it is in nodules that are found in the liver 2 weeks posttreatment. The steady-state level of the constitutive hsp70-related cognate protein (hsc73) mRNA, which is known to be particularly high in fast-growing cells, increases above the normal level only during liver regeneration, stays at a high level up to 8 days after hepatectomy, independently of any associated exposure to carcinogenic chemicals, and is practically unchanged in the nodules. Ornithine decarboxylase mRNA increases only in livers of normothermic rats at 16 h of regeneration. The expression of the c-Ha-ras oncogene increases slightly, but steadily, during the carcinogenic treatment and persists at a high level when other changes have subsided.