Tumour growth delay, cell inactivation and vascular damage following hyperthermic treatment of a human melanoma xenograft.

The effect of hyperthermia at 42.5 degrees C on a human melanoma xenograft in athymic mice was studied. The tumours were heated in vivo in a water-bath. Tumour growth delay and single-cell survival in vitro were used as endpoints. Qualitative information regarding heat-induced vascular damage was obtained from microangiographic analysis. Tumour growth delay after a given treatment was considerably longer than that expected from the cell survival measured in vitro immediately after treatment. Experiments in which removal of the tumours was delayed revealed that tumour cells were continuously dying for at least 24 hr after heat treatment. The volume of the tumour vasculature was considerably reduced after treatment, suggesting that the delayed cell death was attributed to vascular occlusion which resulted in an insufficient supply of oxygen and nutrients and an increased tumour acidity. The present work indicates that at least two mechanisms may be involved in heat-induced cell inactivation in our xenograft: firstly, direct cytotoxic effect of heat; secondly, indirect effect following heat-induced vascular damage.