Hyperthermic potentiation.Biological aspects and applications to radiation therapy

Abstract

Experimental studies have provided evidence that hyperthermia may be an effective agent, either alone or in combination with ionizing radiation, in the treatment of cancer. Results have shown that temperatures in the range of 42 degrees to 45 degrees C: 1) are cytotoxic, with cell lethality showing little or no dependence on levels of oxygenation; 2) inhibit the recovery of cells from sub-lethal and potentially lethal radiation damage while enhancing the levels of lethal damage; and 3) may be combined with x-irradiation in a manner to improve therapeutic ratios. The observed interaction between hyperthermia and x-rays may in part be due to differences in the Age Response Functions and reassortment of cycling cells to these two agents. Hyperthermia may also greatly change repopulation and re-oxygenation parameters in irradiated tumor and normal tissue volumes. An overall consideration of these and other factors is essential in the design of optimal schedules of combined hyperthermia and x-irradiation treatments in the management of malignant disease.

Cellular effects of hyperthermia: relevance to the minimum dose for thermal damage

“…Measurements by Watanabe and Okada 9 using L5178Y cells also show a maximum growth temperature near 408C. The onset of measurable killing over a few hours at 41.5-428C in a number of mammalian cell lines indicates that a sharp transition from growth to killing at a few degrees above body temperature is a general characteristic of mammalian cells 6 . In addition, the theory proposed by Johnson et al 10 to explain the decrease in enzyme activity at elevated temperatures predicts a maximum in enzyme activity near the onset of the denaturation of that enzyme.…”

“…Arrhenius plots of k for killing in the hyperthermic region (figure 2) have a sharp bend at 42-438C 6 , due to the induction of chronic thermotolerance during the survival assay, but there is evidence they are linear for temperatures above this critical temperature to at least 578C 7 . The linear relationship between ln k and 1=T implies that the temperature dependence of the rate constant for killing can be approximated by…”

In vitrothermal therapy of AT-1 Dunning prostate tumours

“…Some of the comparable E values in the literature using 63% injury criteria (i.e. survival drop) are 93 kcal/mole for gliosarcoma cells 45 , 141 kcal/mole for CHO cells 12 , 111 kcal/mole for BAE cells 13 and 127 and 139 kcal/mole for human fibroblasts and V79 cells, respectively 46 . Studies on skin burns pioneered by Henriques 39 and later by other investigators [47][48][49] identified activation energies ranging between 70-150 kcal/mole.…”

Quantitative Differentiation of Both Free 3′-OH and 5′-OH DNA Ends Between Heat-induced Apoptosis and Necrosis

“…With widespread use of the concept of "apoptosis" proposed by Kerr et al (1972), it has been well noted that tumor cells undergo apoptosis or necrosis after various heat loads (Lambert 1912;Dewey et al 1977;Leith et al 1977), although the pathogenesis of heat-induced cell death remains uncertain. Apoptosis was enhanced by mild hyperthermia (a heat load on the order of 42 and 43C for 30 min) both in some normal tissues (Wanner et al 1976;Schrek et al 1980;Allan et al 1987) and in tumor cells (Harmon et al 1989).…”