Dehydroepiandrosterone inhibits DNA synthesis of rat hepatocytes induced by partial hepatectomy or mitogen (ciprofibrate).
In a previous study we have shown that dehydroepiandrosterone (DHEA) inhibits hepatocyte DNA synthesis after short-term administration and induces hepatocellular carcinomas after long-term administration in the rat. It is not known whether DHEA is also capable of inhibiting replicative and mitogen-induced DNA synthesis. In the present study, we have evaluated the effect of DHEA on DNA synthesis in the rat liver after partial hepatectomy and mitogen administration. After partial hepatectomy, DHEA significantly inhibited DNA synthesis at 20, 26, 32 and 38 h. Similarly, combined administration of ciprofibrate, a peroxisome proliferator and mitogen, and DHEA also resulted in significant hepatocyte DNA synthesis. However, DHEA did not affect liver enlargement caused by ciprofibrate. This experimental system will serve as useful tool to evaluate the role of cell proliferation in carcinogenesis.
Rao
M S
MS
Department of Pathology, Veterans Affairs Lakeside Medical Center, Chicago, IL, USA.
Subbarao
V
V
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D058607:Fibric Acids; D006131:Growth Inhibitors / Q000494:pharmacology*; D006498:Hepatectomy; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008099:Liver / Q000166:cytology*; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008830:Microbodies / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344
D058607:Fibric Acids; D006131:Growth Inhibitors; D000960:Hypolipidemic Agents; D003687:Dehydroepiandrosterone; D002995:Clofibric Acid; D004247:DNA; C019304:ciprofibrate