Potentiation of nitrogen mustard cytotoxicity to leukemia cells by sulfur-containing compounds administered in vivo.
Fifteen sulfur-containing compounds were examined for their ability to both protect normal hematopoietic stem cells (NCFU) from the cytotoxic effect of nitrogen mustard (HN2), and potentiate the cytotoxicity of HN2 to AKR leukemia cells (LCFU). All except four agents demonstrated some protection of NCFU with WR-2721 being most active. Five of the agents were also protective for LCFU with cysteine and glutathione being most active. However, a number of agents potentiated the cytotoxicity of HN2 to LCFU, the most active being disulfiram and AET followed by cysteamine, DMSO, WR-638, and WR-3689. The dose-response relationship for the potentiation was defined for DMSO. A second leukemia model, L1210, was also studied for potentiation of HN2 cytotoxicity by four of the most active agents--WR-2721, AET, DMSO, and disulfiram. The first two agents showed no effect (either protection or potentiation) when given either 15 min or 6 hr before HN2 administration. The last two agents, however, potentiated the cytotoxicity to a level similar to that found with the AKR leukemia.
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D007942:Leukemia, Experimental / Q000188:drug therapy*; D008297:Male; D008466:Mechlorethamine / Q000627:therapeutic use*; D051379:Mice; D008806:Mice, Inbred AKR; D011837:Radiation-Protective Agents / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D013440:Sulfides / Q000494:pharmacology
D000596:Amino Acids; D011837:Radiation-Protective Agents; D013438:Sulfhydryl Compounds; D013440:Sulfides; D008466:Mechlorethamine