Heat-induced alterations in cell membrane permeability and cell inactivation of transformed mouse fibroblasts

Hyperthermia, has recently been extended in many permutations as a modality of anticancer treatment, but the mechanisms underlying heat-induced cell inactivation are poorly understood. In this study, the role of the cell permeability barrier in the process of heat cytotoxicity are examined. Changes in cell membrane permeability were determined by following the efflux of normally impermeant metabolites, e.g. nucleotides, in cultures of Swiss mouse 3T3 cells, and their transformed derivatives, 3T6 cells. The increase in cell membrane permeability as a function of temperature and exposure duration was found to be characterized by a sigmoid curve, with a threshold value, above which the permeability markedly increased. A correlation was found between cell membrane permeabilization and cell inactivation. Both heat-induced permeabilization and heat cytotoxicity were more pronounced in the transformed cells, as compared to their untransformed counterparts. The temperature-dependent permeabilization was more effective in the presence of the ionophore amphotericin B. The data suggest that heat-induced lesion in the cell membrane has a major role in hyperthermia cytotoxicity.