In vivo radiosensitization by diethyldithiocarbamate.
Diethyldithiocarbamate (DDC) has been suggested to have both radiosensitizing (due to superoxide dismutase (SOD) inhibition) and radioprotective properties. We have studied the activity of SOD up to 24 h after intratumoral administration of 50, 100, 150, and 300 mg/kg DDC in 3-methylcholanthrene-induced tumors in BALB/c mice. Maximal inhibition of SOD (8% of control) was obtained 1 h after administration of 100 mg/kg DDC. Tumor response to DDC and X irradiation was assessed using a tumor growth-delay assay, after 11 Gy 100-kVp X rays given up to 24 h after DDC administration. Radiation-induced tumor growth delay (7.11 +/- 1.76 days) was enhanced only when tumors were irradiated 2-4 h after 50 mg/kg DDC. When higher doses of DDC were used, tumor cure was noted when DDC was injected 1-6 h before irradiation. We suggest our findings are consistent with radiosensitization being due to SOD inhibition, but that if insufficient time is allowed between DDC injection and irradiation, the sensitization is masked by a radioprotective effect. We believe that further investigations as to the therapeutic potential of DDC in human patients with cancer are warranted.
Kent
C R
CR
Department of Radiotherapy, Groote Schuur Hospital/University of Cape Town, South Africa.
Blekkenhorst
G H
GH
D000818:Animals; D003131:Combined Modality Therapy; D004050:Ditiocarb / Q000627:therapeutic use*; D008297:Male; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D012208:Rhabdomyosarcoma / Q000139:chemically induced / Q000188:drug therapy / Q000532:radiotherapy*; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors
D011838:Radiation-Sensitizing Agents; D008748:Methylcholanthrene; D004050:Ditiocarb; D013482:Superoxide Dismutase