Amphotericin B potentiation of the cytotoxicity of anticancer agents against both normal hematopoietic and leukemia cells in mice.
Dose-response curves in AKR or CD2F1 mice were obtained for AKR leukemia, L1210 leukemia, and hematopoietic stem cells following in vivo administration of one of the following anticancer agents alone or in combination with amphotericin B (AmB): doxorubicin, lomustine, or melphalan. AmB potentiated drug cytotoxicity of all agents against both leukemias. Potentiation of all three agents was greatest with the AKR leukemia demonstrating dose-modifying factor (DMF) values of 1.8, 3.0, and 2.7, respectively, for lomustine, melphalan, and doxorubicin. L1210 leukemia was somewhat less sensitive to drug potentiation by AmB with respective DMF values of 1.8, 1.8, and 1.3. AmB did not potentiate the action of any agent against hematopoietic stem cells. The increased life-span assays generally confirmed the clonogenic assays supporting the validity of the latter results. The specificity of AmB potentiation of anticancer agent cytotoxicity for tumor cells indicates that AmB may be a useful addition to antitumor drug combinations.
D000666:Amphotericin B / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000627:therapeutic use; D004357:Drug Synergism; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D007939:Leukemia L1210 / Q000188:drug therapy; D007942:Leukemia, Experimental / Q000188:drug therapy*; D008130:Lomustine / Q000627:therapeutic use; D008558:Melphalan / Q000627:therapeutic use; D051379:Mice; D008806:Mice, Inbred AKR; D008815:Mice, Inbred Strains
D000970:Antineoplastic Agents; D008130:Lomustine; D000666:Amphotericin B; D004317:Doxorubicin; D008558:Melphalan