Amino acid analogs while inducing heat shock proteins sensitize CHO cells to thermal damage

Amino acid analogs have been shown to induce heat shock proteins (HSPs). We have examined the effect of these analogs on the thermal sensitivity of Chinese hamster fibroblasts (HA-1) and their stable heat-resistant variants. We found that exposure of HA-1 cells and their heat-resistant variants to canavanine or L-azetidine-2-carboxylic acid cause enhanced synthesis of the three major mammalian HSPs (molecular weight 70,000, 87,000, and 110,000 kd). Although the synthesis of HSPs was increased, the analogs did not induce thermotolerance, a transient ability to protect cells from thermal damage. On the contrary, the analog treatment increased the thermal sensitivity of HA-1 cells, but not of the heat-resistant strains, when these cells were exposed subsequently to elevated temperatures. Our tentative explanation for these findings is that the incorporation of amino acid analogs into HSPs or other cellular proteins sensitizes HA-1 cells to heat. The heat-resistant strains contain higher levels of constitutive HSPs. The additional functional HSPs in the heat-resistant variants may protect these cells from thermal stress. The presence of some newly synthesized analog-substituted, perhaps nonfunctional, HSPs need not affect this thermal protection.