Enhancement of heat sensitivity and modification of repair of potentially lethal heat damage in plateau-phase cultures of mammalian cells by diethyldithiocarbamate.

Diethyldithiocarbamate (DDC) is active both in vivo and in vitro in reducing the levels of enzymes such as superoxide dismutase (SOD) and glutathione peroxidase whose role in respiring cells is to remove toxic superoxide radicals and organic hydroperoxides. Although DDC, a copper-chelating agent, has been used to treat benign diseases, its potential as a heat sensitizer has not been fully explored. We have recently shown that the presence of 10(-3) M DDC for 2 hr causes a threefold reduction in the level of SOD in plateau-phase cultures of mammalian cells. At this concentration, the drug causes minimal toxicity but markedly affects both the shoulder and the slope of the heat survival curves. To explore another pathway of DDC sensitization, other than through reduced levels of SOD, we examined the repair of potentially lethal damage with and without DDC following exposure for 1 hr and 40 min at 43 degrees C. The repair, which progressed with a T 1/2 of about 10 hr, in either full medium or Hank's balanced salt solution (HBSS), in the absence of DDC, was completely blocked when DDC was added to the monolayers on completion of the heat exposure. DDC, in view of its ability to potentiate the effects of heat, is a potentially useful drug that could be used in an adjunctive setting with clinical hyperthermia.