The role of apoptosis in the response of cells and tumours to mild hyperthermia.

There is now abundant evidence that apoptosis, the cell death mechanism responsible for physiological deletion of cells, can be triggered by mild hyperthermia. However, the overall importance of this mode of death in heated tumours has not yet been established. In this light and electron microscopic study, apoptosis induced by 43 degrees C or 44 degrees C water bath heating for 30 min in a range of murine and human tumours growing in vitro and in four murine tumours growing as solid nodules in vivo, was identified on the basis of its characteristic morphology, and the amount present quantified. Apoptosis was found to play a variable role in the response of tumours to heating, with the lowest levels produced in human melanoma lines (less than 1%) and the highest levels in some Burkitt's lymphoma lines (up to 97%). In these latter tumours the induction of apoptosis is clearly a major component of the hyperthermic response.

[1]  D. Ucker.  Cytotoxic T lymphocytes and glucocorticoids activate an endogenous suicide process in target cells , 1987, Nature.

[2]  D. Allan,et al.  X-ray-induced cell death by apoptosis in the immature rat cerebellum. , 1988, Scanning microscopy.

[3]  J. Kerr,et al.  Cell death induced in a murine mastocytoma by 42-47 degrees C heating in vitro: evidence that the form of death changes from apoptosis to necrosis above a critical heat load. , 1990, International journal of radiation biology.

[4]  P. Parsons,et al.  The effect of hyperthermia and melphalan on survival of human fibroblast strains and melanoma cell lines. , 1977, Cancer research.

[5]  D. Allan,et al.  The morphologic categorization of cell death induced by mild hyperthermia and comparison with death induced by ionizing radiation and cytotoxic drugs. , 1986, Scanning electron microscopy.

[6]  Hyperthermia and radiotherapy. , 1984 .

[7]  P. Quirke,et al.  Kinetic and Physical Studies of Cell Death Induced By Chemotherapeutic Agents Or Hyperthermia , 1986, Cell and tissue kinetics.

[8]  M. Edwards,et al.  The effect of hyperthermia on the neuroepithelium of the 21‐day guinea‐pig foetus: Histologic and ultrastructural study , 1976, The Journal of pathology.

[9]  G. Hahn,et al.  Effect of hyperthermia (45 degrees C) on calcium flux in Chinese hamster ovary HA-1 fibroblasts and its potential role in cytotoxicity and heat resistance. , 1987, Cancer research.

[10]  M. McMahon,et al.  Hyperthermia and the heat-shock proteins of HeLa cells. , 1982, British Journal of Cancer.

[11]  B. Harmon.  An ultrastructural study of spontaneous cell death in a mouse mastocytoma with particular reference to dark cells , 1987, The Journal of pathology.

[12]  J. Kerr,et al.  Patterns of cell death. , 1988, Methods and achievements in experimental pathology.

[13]  J. Cohen,et al.  Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death. , 1984, Journal of immunology.

[14]  A. Wyllie.  The biology of cell death in tumours. , 1985, Anticancer research.

[15]  R. Schrek,et al.  Two types of interphase death of lymphocytes exposed to temperatures of 37--45 degrees C. , 1980, Radiation research.

[16]  W. Dewey,et al.  Protection of Chinese hamster ovary cells from hyperthermic killing by cycloheximide or puromycin. , 1986, Radiation research.

[17]  A. Wyllie.  Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation , 1980, Nature.

[18]  A. Wyllie,et al.  Cell death: the significance of apoptosis. , 1980, International review of cytology.