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Two Mechanisms of Synergism When Amphotericin B Is Used in Combination with Actinomycin D or 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea against the Human Promyelocytic Leukemia Cell Line HL-60¹

Department of Medicine, Division of Infections Disease [A.V-C., J. B., G. M.], and the Department of Microbiology and Immunology [G. M.], Washington University School of Medicine, St. Louis, Missouri 63110

The toxic effects of the combinations of amphotericin B (AmB) and actinomycin D or AmB and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea were measured against the human promyelocytic leukemia cells HL-60. The toxicities of both drug combinations were greater than the additive toxicity of each of the drugs used singly, but the exact conditions under which synergism was achieved differed for each combination. The synergism achieved by the AmB-actinomycin combination was accompanied by an AmB-induced increase in uptake of actinomycin D by the HL-60 cells, whereas the synergism of the AmB-1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea combination could be linked to potentiation by 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea of AmB-induced oxidative injury. These results indicate that the synergism of these two drug combinations was caused by different mechanisms.

¹ Supported by USPHS Grants AI16228, CA15665, AI07172, and AI07015. Some aspects of this work have already been presented (1).

² Present address: Laboratoire de Physique et Chimie Biomoleculaire (UA CNRS 198), Universite Pierre et Marie Curie, 75252, Paris Cedex 05, France.

³ To whom requests for reprints should be addressed.

Received 3/10/86. Revised 6/18/86. Accepted 8/ 1/86.