Stimulation of survival capacity in heat shocked cells by subsequent exposure to minute amounts of chemical stressors; role of similarity in hsp-inducing effects
Fac. Wiegant et al., Stimulation of survival capacity in heat shocked cells by subsequent exposure to minute amounts of chemical stressors; role of similarity in hsp-inducing effects, HUM EXP TOX, 18(7), 1999, pp. 460-470
1 A brief and moderate heat shock to Reuber H35 hepatoma cells causes a rap
id increase in the synthesis of heat shock proteins (hsp) and initiates the
development of thermotolerance, which results in an increased ability to s
urvive exposure to otherwise lethal temperatures.
2 We now demonstrate that low doses of various chemical stressors (arsenite
, cadmium, mercury, lead, copper, menadione and diethyldithiocarbamate (ddt
c)), at concentrations that do not exert any effect in control cultures, ar
e able to enhance the synthesis of hsps and to stimulate the development of
thermotolerance when applied to cultures which were pretreated with a mild
heat shock.
3 The degree of stimulation appears to be stressor-specific, which is not o
nly observed in the ensuing development of thermotolerance but also in the
enhancement of the heat shock-induced synthesis of stress proteins.
4 The different hsps that show an enhanced induction when heat shocked cult
ures are exposed to the various secondary applied low doses of chemical str
essors, were found to resemble the hsp pattern that is characteristic for t
he secondary stressor and not for the initial heat shock. In other words, t
he nature of the post-treatment determines the observed pattern of enhanced
synthesis of hsps.
5 In order to analyze the origin of the stimulation of survival capacity by
low doses of the mentioned stressors, we studied whether the degree of sti
mulation is determined by the degree of similarity between the overall stre
ss response to heat shock and to the second stress condition when applied s
ingly,
6 The degree in which low doses of chemical stressors stimulate tolerance d
evelopment and enhance the synthesis of hsps in cells that were previously
heat shocked, appears to be related to the degree of similarity in the hsp
pattern induced by both stressors.
7 Our results support the notion that low doses of toxic compounds may, und
er certain conditions, have beneficial effects related to a stimulation of
endogenous cytoprotective mechanisms.