Antitumor activity of 9-hydroxyellipticine (NSC 210717) ON L1210 mouse leukemia and the effect of route of injection.
The antitumor activity of a new derivative of ellipticine, 9-hydroxyellipticine (NSC 210717), was studied using L1210 mouse leukemia. Low doses of this drug have a high antileukemic activity, whereas high doses have less activity than expected because of a leveling off in the antitumor activity-dose relationship, as if a few cells were resistant to the treatment. The possible causes of this apparent resistance were investigated. It is suggested that this apparent resistance is related to the sequestration of a small number of cells in compartments inaccessible to the drug. A model was developed which takes into account the distribution of cells in various compartments and their drug sensitivity therein. It was predicted and observed that the activity of drugs acting on cells in the small compartments can be observed only in conjunction with the presence of drugs acting on the cells in the major compartment. The importance of this observation in the screening procedures of new drugs, the clinical trial of new chemotherapeutic agents, and the association of anticancer drugs are discussed within this context. 9-Hydroxyellipticine is of interest because it acts on leukemic cells in the brain.
D000470:Alkaloids / Q000627:therapeutic use*; D000818:Animals; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004611:Ellipticines / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007939:Leukemia L1210 / Q000188:drug therapy*; D008433:Mathematics; D051379:Mice; D008954:Models, Biological; D009368:Neoplasm Transplantation; D013997:Time Factors
D000470:Alkaloids; D004611:Ellipticines