Induction of thermotolerance in Chinese hamster ovary cells by high (45 degrees) or low (40 degrees) hyperthermia.

Abstract

Abstract Thermotolerance induced in Chinese hamster ovary (CHO) cells by a 45° heat treatment and developed at 37° resulted in an increased D 0 but a reduced extrapolation number, n , of a subsequent 45° heat survival curve. The time course and magnitude of thermotolerance development were dependent upon the conditioning hyperthermia treatment. Within 2 hr after a 10-min exposure to 45°, the n of the subsequent 45° hyperthermia survival curve increased approximately 5-fold with little change in the D 0 . Thereafter, n returned to control values, whereas the D 0 increased by a factor of 5 by 8 hr and then only slowly disappeared at a rate of 0.1 min at 45° per hr of incubation at 37°. A conditioning dose of 5 min at 45° increased the D 0 of the subsequent 45° heat survival curve by a factor of 3.3 within 2 hr, but then the D 0 returned to control values at the same rate as after a conditioning treatment of 10 min at 45°. CHO cells incubated at 40° grew normally without any evidence of cell killing for more than 2 generations, and incubation at 40° for 0 to 7 hr prior to acute heating at 45° did not induce thermotolerance in terms of an increased D 0 . However, the D q of the 45° heat survival curve was increased approximately 3-fold by 40° preincubation for 7 hr. Increasing the incubation temperature from 37 to 39–41° between 45° heat treatments did not alter the thermotolerant D 0 of the subsequent 45° heat survival curve but did reduce n to 1.0. In addition, the survival curves following 45° conditioning and incubation at 39, 40, or 41° were displaced downward by factors of 5.3, 47, and 360, respectively. The enhanced cell killing resulting from post-45° hyperthermia incubation at 39–41° may be due to the conversion of sublethal damage to lethal damage independently of the induction of thermotolerance.