Modification of alkylating agent cytotoxicity by cisplatin.
The effect of cisplatin on the cytotoxicity of alkylating agents in the RIF-1 tumor both in vivo and in vitro was investigated. A single dose of cisplatin (1 mg/kg) enhanced the in vivo tumor killing by melphalan (L-PAM; 8 mg/kg). The effect was maximal when cisplatin was given between 3 hours before and 1 hour after injecting L-PAM; the enhancement was lost as the time interval increased. Similar results were obtained with cyclophosphamide (CYT; 75 mg/kg) and CCNU (50 mg/kg) although the enhancement was much less than that seen with L-PAM. The enhancement by cisplatin was constant at all L-PAM doses as measured by both cloning assay and regrowth delay. Measurements of white blood cell counts four days after drug administration suggests that a therapeutic gain can be achieved. Exponential and plateau phase RIF-1 cells grown in monolayer culture were also exposed to various L-PAM doses. A 1 hour pre-exposure to cisplatin (0.5 micrograms/ml) under aerobic conditions increased the cell killing by L-PAM. The results are discussed with reference to the possible reasons for the therapeutic gain.
D000477:Alkylating Agents / Q000008:administration & dosage*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D008130:Lomustine / Q000008:administration & dosage; D008558:Melphalan / Q000008:administration & dosage; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*
D000477:Alkylating Agents; D008130:Lomustine; D003520:Cyclophosphamide; D002945:Cisplatin; D008558:Melphalan