EFFECT OF HYPERTHERMIA ON AUTOCRINE FUNCTIONS IN TUMOR AND NORMAL-CELLS

It is known that different stress agents, for example heat shock, inte rrupt many cellular functions including growth. We have found that hyp erthermia (44 degrees C, 30 min) of tumour cells of different origin ( human carcinoma and murine sarcoma) induced an increase of the activit y of substances which appeared in the serum-free culture medium condit ioned by these cells and possessed an ability to enhance the intensity of H-3-thymidine incorporation into cellular DNA. The normal NIH-3T3 mouse fibroblasts of cultured for 1-4 h after the termination of heat shock were shown to produce growth inhibiting factors. The substances secreted by the heat-shocked cells also influenced the intensity of pr otein synthesis in the indicator cells. It was found that heat-shocked A-549 carcinoma cells and normal NIH-3T3 fibroblasts cultured for 1-4 h after the termination of hyperthermia produced substances which inh ibited protein synthesis in this line of fibroblasts as well as in the carcinoma A-549 cells. During the longer periods of restoration (6-18 h) the carcinoma cells (but not the normal fibroblasts) secreted stim ulators of protein synthesis. The temporary acidification (pH 2.0, 1 h , 20 degrees C) did not change the protein synthesis regulating activi ty of the conditioned media obtained from the heat-shocked NIH-3T3 cel ls, while an increase of such activity could be observed in the acidif ied serum-free media conditioned by the heat-shocked carcinoma cells. This and some other biological properties of DNA and protein synthesis regulating substances which were detected in the serum-free culture m edium conditioned by the carcinoma cells suggest the role of transform ing growth factor beta in the cellular response to heat shock. The lev els of activities of serine proteinases in the conditioned media from the studied tumour cells and normal fibroblasts and the character of c hanges of these activities under the hyperthermia considerably differ. The character of these changes corresponds to the possible appearance of an active form of transforming growth factor beta which can be rel eased from its latent form under the effect of serine proteinases.