Development of thermotolerance in CHO cells: Modification by procaine

Abstract

We have tested the reported ability of procaine to inhibit the induction and the development of thermotolerance in Chinese hamster ovary cells. Thermotolerance was induced either by hyperthermia alone (10 min, 45 degrees C) or by combining hyperthermia and procaine (5 min, 45 degrees C + 10 mM procaine) with heating times adjusted to yield similar cell survival after the conditioning treatments. Both the kinetics of thermotolerance development in fresh medium without procaine and the magnitude of thermotolerance 6 h after heat conditioning were similar for the two treatment groups. Development of thermotolerance in the presence of procaine was tested by adding the drug at 5 or 10 mM to culture medium between, but not during two fractionated heat treatments. Thermotolerance development was observed even in the presence of 10 mM procaine, but only if cell survival was corrected for the 37 degrees C-procaine toxicity. Complete survival curves of cells incubated for 6 h at 37 degrees C in 7.5 mM procaine between heat conditioning and test heating showed a D0 that was only 35 per cent lower than that of thermotolerant controls. The data are consistent with the reported sensitization to heat killing by procaine, but show that thermotolerance induction and development were only minimally perturbed by procaine.

Heat-induced modulation of lamin B content in two different cell lines

“…However, heat-sensitization by procaine has been reported to proceed by other mechanisms as well, such as by alteration of the association of nuclear protein with chromatin after heat shock [Roti Roti and Wilson, 1984]. Several researchers reported that procaine could inhibit the triggering as well as the induction of thermotolerance [Konings, 1985;Rastogi et al, 1987]. Similarly, through inhibition of heat-induced lamin B synthesis, procaine may increase susceptibility to heatinduced cell killing.…”