Evidence for two states of thermotolerance in mammalian cells

The effect of the inhibition of protein synthesis on the development of thermotolerance in Chinese hamster fibroblasts following a brief heat shock or exposure to sodium arsenite has been examined. Under conditions that inhibit protein synthesis by 95 per cent, significant amounts of thermotolerance develop after a brief exposure to 45 degrees C or continuous exposure to 41 degrees C, without the significant accumulation of heat shock proteins. However, no thermotolerance development in cells treated with sodium arsenite was observed if protein synthesis was inhibited. Heated cells which developed thermotolerance in the absence of protein synthesis are subject to the thermal sensitizing action of subsequent exposure to amino acid analogues, while cells which developed thermotolerance with unimpeded protein synthesis are refractory. These results suggest that heat can simultaneously induce two states of thermotolerance, only one of which is dependent on protein synthesis. These two states can be distinguished operationally with respect to their response to amino acid analogue exposure.