Induction of heat shock gene expression without heat shock by hepatocarcinogens and during hepatic regeneration in rat liver.
We investigated the expression of the rat hepatic heat-shock protein (hsp) genes under the influence of hepatocarcinogens and during hepatic regeneration. This was undertaken because of the inducibility of the heat-shock response in rat liver and because heat-shock genes can be expressed with or without heat shock in various cell states in a developmentally regulated manner. We found that acute administration of hepatocarcinogens to rats induced an increased hsp gene transcription in a time- and dose-dependent manner. Chronic exposure of rats to complete hepatocarcinogens induced increased levels of mainly Mr 83,000 heat-shock protein gene transcription and, to a lesser extent, Mr 70,000 heat-shock protein. However, the tumor promoter phenobarbital did not induce increased hsp gene expression. Increased levels of both Mr 83,000 heat-shock protein and Mr 70,000 heat-shock protein gene transcription were found during hepatic regeneration. Thus, increased hsp gene transcription, which correlated with increased heat-shock protein synthesis, was observed under the acute and chronic influence of hepatocarcinogens and during normal hepatic proliferation. These results are similar to those observed for c-H-ras and c-myc expression in rat liver, and they suggest that a coordinate expression of these three genes may occur in hepatic regeneration and in the early stages of experimental chemical hepatocarcinogenesis.
D015073:2-Acetylaminofluorene; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D004052:Diethylnitrosamine; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism; D008115:Liver Regeneration; D008297:Male; D011519:Proto-Oncogenes; D051381:Rats; D011916:Rats, Inbred F344; D014158:Transcription, Genetic / Q000187:drug effects*
D002273:Carcinogens; D006360:Heat-Shock Proteins; D004052:Diethylnitrosamine; D015073:2-Acetylaminofluorene