STRESSOR-SPECIFIC ENHANCEMENT OF HSP INDUCTION BY LOW-DOSES OF STRESSORS IN CONDITIONS OF SELF-SENSITIZATION AND CROSS-SENSITIZATION

In this paper, the pattern of induction of heat shock proteins (hsps) was studied in cultured Reuber H35 rat hepatoma cells by sequential ap plication of different stressors. We analyzed whether a specific stres s condition is able to induce an enhanced sensitivity to a subsequent application of a low dose of either the same or another stressor (self -sensitization and cross-sensitization, respectively). As a measure of sensitization, the stimulation of hsp induction was employed. Three d ifferent stressor conditions (heat shock, sodium arsenite and cadmium chloride) were used in doses which exerted a similar impact on overall protein synthesis. A synergistic effect in induction of the synthesis of various hsps was observed when a high stressor dose was followed b y an 8-h incubation in a lower stressor dose in both self- and cross-s ensitization experiments. The low-dose conditions used as second treat ments did not induce any responses in non-pretreated cells. Studies in cultured cells have demonstrated stressor specific hsp induction patt erns. In this study we analyzed whether the pattern of hsps induced by the low-dose condition is characteristic for the first sensitizing st ressor or for the secondary stressor applied in a low dose. The patter n of hsps which was induced above the level of the high-dose effect, d ue to the incubation with the secondary applied low-dose condition, wa s found to be characteristic for the secondary stressor and not for th e sensitizing primary treatment. These results are of importance for a n improved understanding of the regulation of heat shock protein synth esis in conditions of self- and cross-sensitization, as well as for a proper use of hsps as biomarkers of exposure to environmental stress. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.