Comparative effect of cisplatin, spiroplatin, carboplatin, iproplatin and JM40 in a human myeloid clonogenic assay.
The relative toxicities of cisplatin and its analogs, spiroplatin, carboplatin, iproplatin and JM40, were tested against normal human progenitor myeloid cells (CFU-GM) in a clonogenic assay. Cells obtained from five bone marrows were incubated for 60 min with various drug concentrations and plated. The mean inhibitory concentrations for 50% of the bone marrow colonies (IC50) were 15.6 micrograms/ml for cisplatin, 0.4 micrograms/ml for spiroplatin, 56.3 micrograms/ml for carboplatin, 36.3 micrograms/ml for iproplatin and 179.5 micrograms/ml for JM40. Ratios of the IC50s of the analogs with cisplatin as reference drug closely followed the corresponding ratios of the clinical maximum tolerated doses. This correlation between the CFU-GM assay results and the clinical myelotoxicity suggests that the assay is adequate for predicting myelotoxicity in vitro and selecting in vitro drug concentrations for the human tumor clonogenic assay.
D000970:Antineoplastic Agents / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects*; D016190:Carboplatin; D002945:Cisplatin / Q000633:toxicity; D003114:Colony-Forming Units Assay; D005069:Evaluation Studies as Topic; D006801:Humans; D009944:Organoplatinum Compounds / Q000633:toxicity
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C038327:ethylenediamine platinum(II) malonate; C023359:iproplatin; D016190:Carboplatin; C040757:spiroplatin; D002945:Cisplatin