Influence of tumour volume and cell kinetics on the response of the solid Yoshida sarcoma to hyperthermia (42 degrees C)

The cytokinetic response of the solid Yoshida sarcoma to hyperthermia was examined at two tumour volumes, 1.0-1.5 ml and 3.0-3.5 ml. The tumour, growing on the feet of rats, was heated at 42 degrees C for 1 h by water-bath immersion. The larger tumour grew more slowly than the smaller one (doubling time 144 h vs 36 h) due to a halving in growth fraction from 67.8 to 39.6% and an increase in cell-loss factor from 59 to 75.9%. Cell cycle and phase times were similar at both volumes. The effect of heat on the population kinetics at both volumes was similar but complex, and involved delayed cell death after up to 10 mitoses. Initial cell killing and blockade of cell-cycle progression (0-24 h) was followed by recovery of proliferation due to recruitment of cells from the non-proliferative compartment, cell cycle and phase times remaining unaltered. From 48 h, the proliferation rate declined progressively, and tumours were completely necrotic 7-8 days after heat. The damaging effects of heat were at least as severe in the large tumours with a low labelling index and small growth fraction as in the smaller tumours with a much larger compartment of proliferating cells and shorter doubling time. The results imply that there may be no simple relationship between proliferative status and thermosensitivity of a tumour, and illustrate the difficulty in predicting tumour response to heat on the basis of cytokinetic studies.