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Development and Decay of Systemic Thermotolerance in Rats¹

Departments of Therapeutic Radiology [D. S. K., Z. W.] and Diagnostic Imaging [P. F. L.], and Section of Comparative Medicine [P. F. L., T. H.], Yale University School of Medicine, New Haven, Connecticut 06510

The development and decay of thermotolerance to the lethal effect of systemic hyperthermia were investigated in Sprague-Dawley rats. Systemic hyperthermia was induced by partial submersion of gas-anesthetized rats in a controlled-temperature water bath. Survival was determined for rats challenged for periods of 10 to 90 min at 42.5° at intervals of 24 to 144 hr after a sublethal conditioning exposure of 41.8° for 1 hr. Survival curves and times of exposure at 42.5° lethal to 50% of the animals (LD₅₀) were determined for the conditioned animals and compared with those obtained for simultaneously treated control (unconditioned) rats. The thermotolerance ratios (LD₅₀ for conditioned animals at various times after sublethal conditioning exposure divided by the LD₅₀ for the control animals) were calculated and compared with the ratios reported in the literature for cells heated in vitro or for tissues heated locally in vivo.

Pretreatment of rats at 41.8° for 1 hr resulted in an increase in the LD₅₀ for rats challenged 24 to 96 hr later, with a maximum increase noted at 48 hr (56.5 min compared with 25 min for control; thermotolerance ratio, 2.3). The animals remained relatively resistant to the second heat treatment at 96 hr and returned to control levels of heat sensitivity by 120 hr. The development and kinetics of thermotolerance to lethality induced by whole-body hyperthermia need to be considered in the design of multiple-fraction treatment plans.

¹ This work was supported by USPHS Grant P06RR00393 from the Animal Resources Branch, NIH; USPHS Grant CA 16359-06; and Grant IN-31-U-7 from the American Cancer Society.

² To whom requests for reprints should be addressed, at Department of Radiology, Division of Radiation Therapy, Stanford University School of Medicine, Stanford, California 94305.

Received 3/28/83. Accepted 12/16/83.

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