DISTRIBUTION OF FLUOROURACIL-2-C14 IN HYPOTHERMIC ANIMALS WITH NORMOTHERMIC TUMORS

It has been shown previously that normothermic tumors of deeply cooled hamsters regress and eventually disappear6, 8 In order to induce complete disappearance of the tumors the duration of differential hypothermia must be at least 10 hrs. A more shallow differential hypothermia causes the same changes but the exposure time has to be increased from 10 to 24 hrs.7 However, when 5-fluorouracil, an anticancer drug, is simultaneously applied with generalized body cooling and tumor warming, only 1 hr is needed to lead to the same results. The purpose of the study- reported here wasto elucidate the mechanism of tumor disappearance resulting from the combination of fluorouracil with brief differential hypothermia. As a first step in this direction the distribution of C14-labeled fluorouracil was studied in the organs of 10S hamsters cooled to a body temperature of 4°C while their tumors were kept normothermic. After intravenous administration of FU-2-C14, the radioactivity of blood of these animals remained at a high level whereas it fell quickly to very low levels in normothermic animals. It is therefore concluded that the differential hypothermia acts as a long-term systemic perfusion affecting preferentially the warm tumor tissue because of its larger blood circulation and its higher metabolism. © 1969.