Tolerance Induction and Stress Proteins

Gerner and Schneider (1975) were the first to demonstrate that heat shock induces a transient state of heat resistance in mammalian cells. Subsequent research has demonstrated that cells or embryos given a sublethal heat shock sufficient to induce hsp synthesis exhibit tolerance to an otherwise lethal heat shock (Li and Laszlo 1985 Mirkes 1987 Johnston and Kucey 1988 Riabowol et al. 1988). This phenomenon has been termed acquired thermotolerance, and is defined for the purposes of this review as selftolerance. Data from numerous studies demonstrate that the acquisition of thermotolerance is attributable to the induction and expression of stress proteins (Landry et al. 1982 Welch and Mizzen 1988). Many investigations, including those of Landry et al. (1982), Li and Werb (1982), and Lavoie et al. (1993), have demonstrated that the kinetics of thermotolerance induction and decay are correlated with stress protein synthesis and degradation, respectively. 

A considerable number of stress protein inducers, such as cadmium, ethanol, and sodium arsenite, are as effective as heat in conditioning the cell to become thermotolerant. This type of tolerance, where the inducing and stress stimulus are different, is termed cross-tolerance. Induction of cross- 

In contrast to the cross-tolerance studies described above employing arsenic, similar experiments reported that cadmium induces self-tolerance (Cervera 1985), but pretreatment with zinc or cadmium generally does not confer thermotolerance in cultured cells (Cervera 1985) and sea urchin embryos (Roccheri et al. 1988). Heat pretreatment does not confer crosstolerance to cadmium in cultured cells (Cervera 1985 Ciavarra and Simeone 1990a,b), although a few exceptions have been reported. Kapoor and SvEENiVASAN (1988) demonstrated that cadmium chloride treatment led to the induction of high levels of peroxidase activity and induced thermotolerance in the mold Neurospora crassa, although no correlation between levels of superoxide dismutase and the development of thermotolerance could be established. 

The genetic differences in heat-induced cross-tolerance to cadmium were investigated in two inbred strains of mice (Kapron-Bras and Hales 1992). Although pre-exposure to heat provided no cross-tolerance to cadmium in BALB/c mouse embryos, heat treatment of SWV mouse 

Because of the diversity of the stress response in various organisms in response to different stressors, it is difficult to make generalities regarding the involvement of any specific stress protein in the establishment of tolerance to metals and other xenobiotics. Additional research is needed to determine which of these stress proteins, if any, are essential for the induction of self- and cross-tolerance to metals and other stressors, and to elucidate other physiologic mechanisms which may be involved in this phenomenon. 

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