Heat shock proteins: role in thermotolerance, drug resistance, and relationship to DNA topoisomerases.

The events following a mild heat exposure to cells that appear to be closely linked are: enhanced synthesis of hsp's and thermotolerance. In some cases, thermotolerance is also associated with drug resistance. We have recently examined the role that DNA topoisomerase II may play in the induction of these phenomena. VM-26 was found to both initiate hsp synthesis and to cause thermotolerance. Furthermore, the permanent heat resistant or transient thermotolerant cells were more resistant to VM-26 than controls. These results suggest that topoisomerase II, or more likely topoisomerase II-DNA complexes, are affected by heat or by VM-26 in a phenomenologically overlapping manner. Elevated levels of hsp's apparently protect cells against the cytotoxic action of both heat and VM-26.