ENHANCEMENT OF THE STRESS-RESPONSE BY MINUTE AMOUNTS OF CADMIUM IN SENSITIZED REUBER H35 HEPATOMA-CELLS

The aim of this study was to determine whether the cadmium-induced cel lular stress response can be modulated by the subsequent application o f low concentrations of the same ion. It is shown that exposure of Reu ber H35 rat hepatoma cells to cadmium concentrations of 10 or 30 mu M for 1 h leads to a biphasic change in their sensitivity towards a seco nd exposure to cadmium, an initial sensitization is followed by develo pment of tolerance towards the secondary treatment with cadmium. Furth ermore, incubations for 1 h in the presence of 10 mu M of cadmium indu ce the synthesis of the major heat shock proteins except for hsp60. A step-down cadmium regime, i.e. a pretreatment of 1 h with 10 or 30 mu M immediately followed by incubations with lower concentrations of cad mium (ranging from 0.03 to I mu M), leads to additional increases in h sp synthesis. Since no effect of these low concentrations was observed on hsp synthesis in non-pretreated cells, the effect of a step-down t reatment thus results in a higher effect on hsp synthesis than could b e expected based on their summation. The sensitized cells also develop a higher level of tolerance in the presence of the above mentioned lo w concentrations of cadmium. It can be concluded that during the trans ient period of enhanced sensitivity, low concentrations of the origina l stressor enhance the synthesis of hsps and thus induce higher levels of tolerance in comparison with cells which only received the primary cadmium treatment. Copyright (C) 1997 Elsevier Science Ireland Ltd.