Interaction of Thermotolerance and Thermosensitization Induced in CHO Cells by Combined Hyperthermic Treatments at 40 and 43°C

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Abstract
Thermotolerance was induced in Chinese hamster ovary cells by heating at 40.degree. C for various times prior to hyperthermia at 43.degree. C. The D0 [mean LD] of the 43.degree. C heat survival curve (D0 = 16.8 .+-. 1.5 min) increased about linearly with the duration of pretreatment at 40.degree. C for up to 12 h at a rate of 10.6 .+-. 0.7 min/h of pretreatment. Thermotolerance (in terms of enhanced D0) decayed exponentially with fractionation interval at 37.degree. C; the half-time was 3.8 .+-. 0.3 h as determined after conditioning at 40.degree. C for 12 h. Thermosensitization was observed after priming treatments at 43.degree. C that increased the sensitivity of the cells to a subsequent heating at 40.degree. C by as much as a factor of 100 depending on the duration of pretreatments; the D0 of the 40.degree. C heat survival curve (43 .+-. 15 h) was reduced to 0.43 .+-. 0.04 h when a priming treatment at 43.degree. C for 90 min was given prior to heating at 40.degree. C. Thermosensitization decayed exponentially with incubation time at 37.degree. C; the half-time was 2.8 .+-. 0.3 h as determined for the 43.degree. C, 60 min .fwdarw. 37.degree. C .fwdarw. 40.degree. C schedule. The interaction of thermotolerance and thermosensitization was demonstrated for the sequence 40.degree. C, t1 .fwdarw. 43.degree. C, 90 min .fwdarw. 40.degree. C. Pretreatments at 40.degree. C for the time t1 caused an increase in survival due to induction of thermotolerance and gradually suppressed the development of thermosensitization depending on the duration of pretreatment. The D0 of the 40.degree. C post-treatment curve increased linearly with pretreatment time t1, from D0 = 0.43 .+-. 0.04 h for t1 = O to D0 = 34 .+-. 12 h for t1 = 16 h, indicating that the induction of thermosensitization is almost completely suppressed by a 40.degree. C treatment for 16 h prior to 43.degree. C hyperthermia. [Hyperthermia is currently used in the treatment of cancer.].