ENHANCEMENT OF HYPERTHERMIC TOXICITY BY LONIDAMINE IN THE DUNNING R3327G RAT PROSTATIC ADENOCARCINOMA

Hyperthermia alone or with radiation is used therapeutically for local ized solid tumors. Clinical experience shows that sustained tumor temp erature exceeding 45 degrees C damages normal tissue. Any agent that e nhances the effects of hyperthermia at or below this temperature may h ave clinical relevance. Lonidamine and hyperthermia were tested on the Dunning R3327G rat prostatic adenocarcinoma. Using colony-formation a ssays, cytotoxic effects of each agent alone and in combination were q uantified. Lonidamine to 100 mu g/ml was not significantly toxic, but in combination, it enhanced cytotoxicity. Survival patterns after frac tionated hyperthermia revealed a rapid development and decay of thermo tolerance. Measurement of cell-cycle progression following a single do se of hyperthermia revealed a reduction of S-phase cells, and subseque nt accumulation in G(1) over 24 hours. Combination treatment of tumor- bearing rats significantly reduced tumor growth rate when compared wit h individual agents. These results suggest a potential use of lonidami ne in hyperthermic therapy of prostate tumors. (C) 1994 Wiley-Liss, In c.