Heat shock response by cells treated with azetidine-2-carboxylic acid

The purpose of this study is to reinvestigate the heat shock response in cells treated with the antimetabolite azetidine-2-carboxylic acid (azetidine), an analogue of proline. Previous studies could not clearly discriminate between the progressive thermosensitization caused by amino acid analogues and a parallel induction of thermotolerance by heat shock. Incubation of H35 cells with 2.5 mm azetidine causes an increasing thermosensitization which achieves a maximum after approximately 18-22 h. At this point, azetidine does not prevent the development of acute thermotolerance following a heat shock at 42.5 C, or the simultaneous induction of chronic thermotolerance during mild hyperthermia at 38-41 C. However, for both the acute and chronic heating conditions thermotolerance levels are reduced in proportion with azetidine-thermosensitization. Incorporation of azetidine causes an apparent downward temperature shift of approximately 1 C relative to the time-temperature relationships for normal, or following ...