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Enhancement of 5-Fluorouracil Action on Normothermic Tumors by Generalized Hypothermia¹

Department of Physiology, Emory University, Atlanta, Georgia

In experiments reported earlier it has been shown that subsequent to cooling of the whole body of golden hamsters their normothermically kept tumors disappear (11–13). However, in order to induce tumor disappearance the differential hypothermia (tumor-body) has to last at least 10 hr. Since extreme hypothermia lasting several hours is not well tolerated by nonhibernators, experiments were now undertaken in which the differential hypothermia was combined with 5-fluorouracil (FU), an anticancer drug. It was reasoned that the anticancer durg might become preferentially effective in the tumor tissue because of higher volume blood flow as well as of higher metabolic rate of normothermic tumors when compared with the rest of the hypothermically kept body. For this purpose the bodies of 75 hamsters were cooled to a temperature of 4°C while their tumors (Toolan H. Ad. No. 1U) remained uncooled at 37°C. The FU (50 mg/kg) was administered i.v. in a single injection. One hr later the animals were rewarmed. Twenty days later all tumors regressed and disappeared completely without resuming their growth afterward. When the same amount of FU was administered into normothermic tumor-bearing animals or into hypothermic animals with hypothermic tumors, neither tumor size nor body weight of the animals was affected.

¹ This investigation has been supported by Research Grants GM-09652 from the National Institute of General Medical Sciences and CA-06311 from the National Cancer Institute. It is listed as Publication No. 701, Division of Basic Health Sciences, Emory University.

Received 4/18/66. Accepted 6/ 8/66.