Factors influencing the toxicity of diethylaminoethylreserpine to tumor cells: studies with four transplantable tumors.
The toxicity of 1-[2-(diethylamino)ethyl]reserpine (DL-152) has been measured for 4 transplantable mouse tumors. DL-152 was found to be toxic to cells of all the tumor models tested (KHT fibrosarcoma, RIF-1 fibrosarcoma, EMT-6 adenocarcinoma and Lewis lung carcinoma) when the drug was given by intraperitoneal injection to the tumor-bearing mouse and cell survival was measured by excision assay. For the KHT tumor, hypoxic cells were found to be more sensitive to the drug in vivo than were aerated cells, and a similar response to hypoxia was observed in vitro, suggesting that sensitization occurred at the cellular level. Neither EMT-6 nor RIF-1 tumors showed increased sensitivity to the drug when cells were exposed under hypoxic conditions in vivo or in vitro. However, when the response of aerated cells of the 3 tumors was compared, the relative sensitivities for tumors exposed in vivo did not show the same ranking as the results of in vitro toxicity assays. This difference in in vitro and in vivo response in the different tumor models did not appear to be related to pharmacokinetic factors since the maximum tissue concentration and the rate of clearance of the drug were similar for all the tumors studied.
Lehnert
S
S
Department of Radiation Oncology, McGill University, Montreal, Canada.
D000230:Adenocarcinoma / Q000188:drug therapy*; D000332:Aerobiosis; D000818:Animals; D002277:Carcinoma / Q000188:drug therapy*; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D012110:Reserpine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay
C004538:bietaserpine; D012110:Reserpine