Cytotoxicity and sister chromatid exchanges induced in vitro by six anticancer drugs developed in the People's Republic of China.
Growth inhibition in the Chinese hamster cell line V79 and in the human lymphoid cell line Raji and induction of sister chromatid exchange(s) (SCE) in V79 cells after treatment with six anticancer drugs [harringtonine (HRT), homoharringtonine (HHRT), camptothecin (CPT), hydroxycamptothecin (HCPT), lycobetaine (LBT), and oxalysine (OXL)] developed in the People's Republic of China were studied. OXL is a new antibiotic; all other drugs are plant extracts. All drugs caused a dose-dependent growth inhibition in both cell types, as evidenced by decreases in plating efficiencies of V79 cells and in viable cell counts of Raji. However, the degree of inhibition differed widely among the drugs. HRT, HHRT, CPT, and HCPT were the most potent growth inhibitors, LBT was next, and OXL was the least effective inhibitor. SCE analyses were made in V79 cells treated with a drug in the presence or absence of the metabolic activation system S9 mixture (S9 mix), except for the HRT assay in which the S9 mix was not used. CPT, HCPT, and LBT induced a dose-dependent increase in SCE frequencies, while HRT, HHRT, and OXL caused no SCE induction at any dose level used. CPT was the most powerful SCE inducer. HCPT induced SCE but at a much reduced rate when compared to that of CPT. LBT was a weak SCE inducer; SCE induction was seen only in cultures treated with 40 micrograms or more LBT/ml. Addition of the S9 mix did not alter SCE frequencies, indicating that the drugs were direct-acting agents. HRT and HHRT were highly toxic, but they induced no increases in SCE frequency, indicating that cytotoxicity of a compound does not necessarily correlate with SCE induction.
D000470:Alkaloids / Q000633:toxicity*; D047151:Amaryllidaceae Alkaloids; D000600:Amino Acids, Dicarboxylic; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D002166:Camptothecin / Q000031:analogs & derivatives*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002681:China; D006224:Cricetinae; D003412:Cricetulus; D003434:Crossing Over, Genetic / Q000187:drug effects*; D006248:Harringtonines / Q000633:toxicity*; D000077863:Homoharringtonine; D006801:Humans; D007212:Indolizines; D008168:Lung; D008221:Lymphoid Tissue; D009152:Mutagenicity Tests; D012694:Serine / Q000031:analogs & derivatives* / Q000633:toxicity; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D000470:Alkaloids; D047151:Amaryllidaceae Alkaloids; D000600:Amino Acids, Dicarboxylic; D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D006248:Harringtonines; D007212:Indolizines; C016175:ungeremine; D012694:Serine; D000077863:Homoharringtonine; C027136:4-oxalysine; D002166:Camptothecin