Synergistic cytotoxicity of combinations of dimethyl sulfoxide and antineoplastic agents against P388 leukemia in CD-F1 mice.
We have reported that dimethyl sulfoxide (DMSO) and antineoplastic agents exhibit synergistic cytotoxicity against human tumors in vitro. This study was undertaken to investigate this effect in vivo. Groups of mice were given intraperitoneal (i.p.) injections of P388 leukemia cells. Groups were treated with i.p. injections of either saline, DMSO alone, mitoxantrone hydrochloride (DHAD) alone, methotrexate alone, DHAD in DMSO or methotrexate in DMSO. Combinations of DMSO and DHAD produced 46-61% increases above expected survival, demonstrating synergistic cytotoxicity in vivo. Following confirmatory animal studies, trials utilizing i.p. delivery of antineoplastics in DMSO as treatment for peritoneal tumors should be undertaken.
Pommier
R F
RF
Department of Surgery, Oregon Health Sciences University, Portland 97201-3098.
Woltering
E A
EA
Milo
G
G
Fletcher
W S
WS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004357:Drug Synergism; D007941:Leukemia P388 / Q000188:drug therapy* / Q000473:pathology; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D008942:Mitoxantrone / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D008942:Mitoxantrone; D008727:Methotrexate; D004121:Dimethyl Sulfoxide