Yang C M, Deng J F, Chen C F, Chang L W
Department of Pharmacology, Chang Gung Medical College, Tao Yuan, Taiwan, China.
Biomed Environ Sci. 1994 Sep;7(3):259-65.
The biochemical mechanism underlying the toxicity of podophyllotoxin is investigated. Previous studies from our laboratories suggested that hepatocytes were extremely sensitive to the toxicity of podophyllotoxin and a disruption of protein synthesis was suspected. Dose-response and time-course studies on the effects of podophyllotoxin on protein. RNA, and DNA syntheses on hepatocellular cultures were made. Inhibitions of protein, RNA, and DNA syntheses were demonstrated, and a direct correlated dose-response relationship on such effects was also evident. Inhibition of protein synthesis appeared to be a direct toxic effect of podophyllotoxin and occurred independently from that of RNA. The reduction of DNA synthesis was reflected by a reduction of H3-thymidine incorporation, which is believed to be the consequence of inhibition on the mitotic activity by podophyllotoxin.
对鬼臼毒素毒性的生化机制进行了研究。我们实验室之前的研究表明，肝细胞对鬼臼毒素的毒性极其敏感，怀疑蛋白质合成受到了干扰。对鬼臼毒素对肝细胞培养物中蛋白质、RNA和DNA合成的影响进行了剂量反应和时间进程研究。结果表明蛋白质、RNA和DNA合成均受到抑制，且这种影响呈现出直接相关的剂量反应关系。蛋白质合成的抑制似乎是鬼臼毒素的直接毒性作用，且独立于RNA的抑制作用而发生。DNA合成的减少通过H3-胸腺嘧啶核苷掺入量的减少得以体现，这被认为是鬼臼毒素抑制有丝分裂活性的结果。
