ENHANCEMENT OF THERMAL-DAMAGE IN MURINE TUMORS BY HYDRALAZINE-INDUCEDMODIFICATION OF BLOOD-FLOW AND OXYGEN-TENSION

We investigated changes in blood flow in normal muscle and in SCC-VII tumors treated by hyperthermia combined with hydralazine, to evaluate the enhancement of thermal tumor damage by hydralazine. We studied SCC -VII tumor-bearing C3H/He mice. Hydralazine was administered by intrap eritoneal injection, and tumors were heated by a water bath. We measur ed blood flow using the laser Doppler method, and oxygen tension using polarography. The response of tumors to therapy was assessed using a growth delay analysis. In tumors, blood flow and O-2 tension significa ntly decreased with increasing doses of hydralazine. Compared to tumor s treated by hydralazine alone or by hyperthermia alone, tumor blood f low was significantly decreased in the group treated by hyperthermia w ith hydralazine. In tumors treated by hyperthermia with hydralazine, b lood flow was significantly decreased with increasing Hyd doses, heat durations, and temperatures. In normal muscle, no decrease in blood fl ow was induced by hyperthermia, hydralazine, or their combination. In tumors treated by hyperthermia (43 degrees C, 20 min) with hydralazine , a maximum additional growth delay was observed. Our results suggest that a decrease in tumor blood flow caused by hydralazine plays an imp ortant role in enhancement of the hyperthermic antitumor effect.