title: Experimental podophyllotoxin (bajiaolian) poisoning: III. Biochemical bases for toxic effects.
abstract: 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.
authors.affiliation: Department of Pharmacology, Chang Gung Medical College, Tao Yuan, Taiwan, China.
authors.forename: C M
authors.initials: CM
authors.lastname: Yang
authors.forename: J F
authors.initials: JF
authors.lastname: Deng
authors.forename: C F
authors.initials: CF
authors.lastname: Chen
authors.forename: L W
authors.initials: LW
authors.lastname: Chang
mesh_terms: D002478:Cells, Cultured / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D011034:Podophyllotoxin / Q000633:toxicity*; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis
chemical_list: D012313:RNA; D004247:DNA; D011034:Podophyllotoxin