Experimental podophyllotoxin (bajiaolian) poisoning: III. Biochemical bases for toxic effects

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.