Hyperthermia, cyclosporine A and melphalan cytotoxicity and transport in multidrug resistant cells

The ability of hyperthermia and cyclosporine A to modulate melphalan cytoto xicity and transport processes was investigated in a pleiotropic MDR Chines e hamster ovary cell line (CH(R)C5) and in the drug-sensitive parent line ( AuxB1). Cyclosporine A increased cytotoxicity of melphalan in MDR cells, bu t not in drug-sensitive cells. In MDR cells,hyperthermia caused marked enha ncement of melphalan cytotoxicity when cyclosporine A was present. The incr eased melphalan cytotoxicity in MDR cells was accompanied by changes in mem brane permeability to the drug. Cyclosporine A caused an increase in melpha lan uptake in MDR cells and a decrease in melphalan efflux out of cells, le ading to an overall increase in intracellular drug accumulation. Drug trans port processes were not affected by cyclosporine A in drug-sensitive cells.