Effects of 10-hydroxycamptothecin on chromatin protein synthesis in murine hepatoma cells

10-hydroxycamptothecin (HC) is a new antitumor alkaloid isolated from Camptotheca acuminate indigenous to China. After 60-min incubation of hepatoma cells with 50-200 microM HC in vitro, the syntheses of histome and non-histone protein (NHP) in nuclei were inhibited gradually while the syntheses of cytoplasmic and nuclear sap proteins (0.15 M NaCl soluble part) were much less altered. In mice bearing ascites hepatoma, 4 h after ip HC 0.5-10 mg/kg an obvious dose-dependent inhibitions of histone and NHP synthesis were observed, but the reductions in syntheses of cytoplasmic and nuclear sap proteins did not appear until ip HC 10 mg/kg/d for 3 d. It suggested that HC was more potent on chromatin protein synthesis than others. The time course of its effects on syntheses of DNA, histone and NHP both in vitro and in vivo indicated that the initial peak, and recovery of suppressive effect caused by HC occurred essentially at the same time. Scuh findings were coincident with the concept of tight coupling of synthesis of DNA and chromatin protein, particularly histone. Bleomycin A5, a DNA single-strand scissor, inhibited the synthesis of histone and NHP only, while homoharringtonine, actinomycin D, and nitrocaphane produced the depressive influences on synthesis of all kinds of proteins.