PROTECTION OF 5-ALPHA-DIHYDROTESTOSTERONE AGAINST TGF-BETA-INDUCED APOPTOSIS IN FAO CELLS AND INDUCTION OF MITOSIS IN HEPG(2) CELLS

Administration of TGF-beta 1 to both FaO and HepG(2) cells significant ly induced apoptosis, particularly in FaO cells. Degradation of genomi c DNA in FaO cells was rapidly induced by treatment with TGF-beta 1 (5 ng/ml) for only 4 hr. 5 alpha-dihydrotestosterone (DHT, 25 nM) alone did not affect any significant changes in cell viability and in nuclei of FaO cells; however, pre-treatment with DHT protected genomic DNA d egradation induced by TGF-beta 1 for 14 hr. Simultaneous treatment wit h DHT plus TGF-beta 1 (D + T) inhibited TGF-beta-induced apoptosis by approximately 50% in FaO cells, On the other hand, D + T treatment inc reased mitosis in actively growing HepG(2) cells. Thus, it is reasonab le to conclude that DHT gives growth advantage to hepatocellular-carci noma cells by inhibiting TGF-beta-induced DNA fragmentation in FaO cel ls and by inducting mitosis in HepG(2) cell. (C) 1997 Wiley-Liss, Inc.