DIETHYLDITHIOCARBAMATE ENHANCEMENT OF RADIATION AND HYPERTHERMIC EFFECTS ON CHINESE-HAMSTER CELLS INVITRO

To test the possibility of enhancing O2- toxicity during radiation therapy and/or hyperthermia, Chinese hamster cells (Don) were treated with the drug diethyldithiocarbamate (DDC) in vitro. This drug has been shown to inhibit, both in vitro and in vivo, the enzyme superoxide dismutase (SOD) which is responsible for eliminating the O2- radical in cells. We observed that the cytocidal effect of DDC on Don cells is dependent on both DDC concentration and exposure time. After 8 to 10 days of incubation with 10-9 M DDC, no change in cell survival was noted; however, incubation with 10-4 M DDC produced a marked loss in colony formation. When DDC-treated cells were γ-irradiated, they did not survive as well as the cells that were treated with either radiation or DDC alone. The combined effects of hyperthermia and DDC were dramatic. Cells treated 5 min at 43°C with 10-4 M DDC or 10 min at 43°C with 10-5 M DDC showed significant decrease in survival. These results suggest that DDC may be a potentially powerful sensitizing agent in tumor therapy, since there is increasing evidence that tumor cells have a lower level of superoxide dismutase.