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Hyperthermic Enhancement of Rhodamine 123 Cytotoxicity in B16 Mouse Melanoma Cells in Vitro

Department of Surgery, Division of Surgical Oncology, University of California, Davis, Sacramento, California 95817

The effect of elevated temperature on cytotoxicity of rhodamine 123 (R123) was tested in vitro on B16 mouse melanoma cells. Simultaneous 1-h exposure to R123 and hyperthermia (43°C for 1 h) resulted in marked enhancement of R123 cytotoxicity. Thermal enhancement of R123 cytotoxicity occurred at temperatures as low as 38°C. Heat treatment (43°C for 1 h) given immediately before or after R123 exposure (37°C for 1 h) yielded no significant increase in cytotoxicity over that expected for strict additivity. The effects of heat on two mechanisms reported to be associated with R123 cytotoxicity were evaluated: (a) target inactivation by R123; and (b) R123 intracellular accumulation. Hyperthermia caused an increased rate of target inactivation by R123 and also caused an increased net intracellular accumulation of R123. This indicates that at least two mechanisms are responsible for the synergistic cytotoxicity of R123 and hyperthermia.

¹ Recipient of an American Cancer Society Clinical Oncology Career Development Award (CDA 87-97). Supported in part by the Miloslavich Cancer Research Fund. Research conducted at the Comparative Cancer Center, University of California, Davis School of Veterinary Medicine. To whom requests for reprints should be addressed.

Received 1/17/89. Revised 5/18/89.