The effect of hyperthermia on cell survival in a mouse tumour without bloodflow

In a series of experiments to study the effect of hyperthermia on mouse tumours, Crile (1962; 1963) observed that application of a tourniquet to the tumour-bearing leg greatly enhanced the heat damage to the tumour. Suit (1977) also observed that heating a C3H mammary carcinoma under clamp-induced hypoxic conditions retarded growth of the tumour significantly more than did heating under normal conditions. More recently, a similar observation was reported by Hill and Denekamp (1978) using a squamous cell carcinoma of WHT mice. These workers observed that occlusion of blood supply to the tumour by application of a metal clamp during hyperthermia significantly increased the frequency of tumour eradication by hyperthermia. Morris et al., (1977) reported that clamping sensitized the tail of rats to heat by a factor of about three, suggesting that normal tissues also became sensitive to heat when their blood flow is occluded. No information has been available, however, on the effect of occluded blood supply during hyperthermia at the cell survival level. In the present work we investigated the heat-induced change in the number of clonogenic cells in tumours in which blood flow had ceased completely prior to hyperthermia. We used the SCK tumour, which grows in A/J mice, with a volume doubling time of approximately two days, and forms clones when cultered in vitro. About 5 × 104 single cells were inoculated subcutaneously into the leg of A/J mice, and when they grew to 7–9 mm diameter hyperthermia was applied by immersing the tumour-bearing leg into water heated to 43.5 or 44.5°C.