Induction of thermotolerance and sensitization in CHO cells by combined hyperthermic treatments at 40 and 43°C

Abstract

Chinese hamster ovary cells exposed to combined hyperthermic treatments at 40 and 43°C showed an increase or decrease in cellular sensitivity depending on the temporal order of the application of the two temperatures. Treatments at 40°C prior to hyperthermia at 43°C induced pronounced thermoresistance; the D o of the subsequent 43°C survival curves increased by factors of 1.1, 1.9 or 3.5 and the D q by factors of 2.2, 2.4 or 2.5 for a 1, 3 or 5-hr pre-treatment, respectively. The magnitude of thermotolerance is fully developed by the end of pre-treatment and is not further enhanced by an incubation at 37°C following the 40°C pre-treatment. When the two thermal doses are separated by incubation at 37°C, the magnitude of thermotolerance remained constant for about 2 hr followed by a slow decline. After 24 hr at 37°C, survival is still considerably higher than expected without induced thermotolerance. If the order of the two hyperthermic treatments is reversed, CHO cells are rendered sensitive to 40°C, which is virtually non-lethal when it is not preceded by high hyperthermia. After hyperthermic treatments at 43°C for 30 or 60 min, inactivation at 40°C occurs exponentially, the D o amounting to 1.88 ± 0.03 hr and 1.49 ± 0.08 hr, respectively. This sensitization completely disappears in the course of 7 hr when the cells are incubated at 37°C after conditioning with 43°C hyperthermia.