Effects of 10-hydroxycamptothecin on chromatin protein synthesis in murine hepatoma cells
Ling, Y.H.; Zhao, C.S.; Xu, B.
Zhongguo Yao Li Xue Bao 7(3): 285-288
1986
ISSN/ISBN: 0253-9756 PMID: 2954382 Document Number: 277080
10-Hydroxycamptothecin (HC) is a new antitumor alkaloid isolated from Camptotheca acuminata indigenous to China. After 60-min incubation of hepatoma cells with 50-200 .mu.M HC in vitro, the syntheses of histone 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 .times. 3 d. It suggested that HC was more active or chromatin protein synthesis than others. The time course of its effects on syntheses 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. Such findings were coincident with the concept of tight coupling of synthesis of DNA and chromatin protein, particularly histone. Bleomycin A 5, a DNA single-strand scissor, inhibited the syntheses of histone and NHP only, while homoharringtonine, actinomycin D, and nitrocaphane produced the depressive influences on syntheses of all kinds of proteins.