Thermotolerance in human cells of normal and neoplastic origin

Abstract

Thermotolerance was assayed under controlled conditions in normal and neoplastic human cells with the aim of identifying intrinsic differences in the acquisition of heat resistance. Carcinoma cells from colon (WIDR) and lung (A-549) were compared to fibroblasts (AG-1522) and primary explants of umbilical vein endothelial cells (HUVEC) in terms of their response to a 20 min heat shock at 45°C. Single cell survival, heat shock protein (HSP) synthesis, and glutathione were studied as common endpoints. Production of HSPs was immediate in normal derived cells, and was evident in neoplastic cells 2h following heat shock. Maximum translation of 70 and 90 kDa HSPs was observed at 6 h in all cell types and ceased by 24 h. Maximum cell survival peaked 4-24 h after the second heat dose showing a close association with HSP synthesis. Thermotolerance developed rapidly and decayed slowly over the next 5 days in normal and transformed cells. There was no correlation between the development of thermotolerance and endogenous glutathione content in all cells.

There is little to distinguish thermotolerance in normal and neoplastic cells when compared on an equal basis as demonstrated here, indicating that therapeutic gain in vivo may be largely dependent on tumour physiology.

Key Words:

• cell survival
• heat shock proteins
• glutathione
• normal and neoplastic cells