Potentiation of the activity of cisplatin and cyclophosphamide by trimidox, a novel ribonucleotide reductase inhibitor, in leukemia-bearing mice.
We describe the use of the new ribonucleotide reductase inhibitor, trimidox (TDX), in combination chemotherapy under in vitro and in vivo conditions with cisplatin and cyclophosphamide. In vitro, the combination of TDX and cisplatin was tested in L1210 cells. The combination caused concentration dependent antagonistic or additive effects. However, the combination of TDX-cisplatin-cyclophosphamide in vivo is highly synergistic in both, the L1210 and P388D1 leukemia mouse models. Both combinations, TDX with cisplatin or TDX with cyclophosphamide were also synergistic in the L1210 and P388D1 leukemia animal models.
Novotny
Ladislav
L
Faculty of Pharmacy, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait, and Clinical Institute of Medical and Chemical Laboratory Diagnostics, General Hospital of Vienna, Austraia. novotny@hsc.edu.kw
Rauko
Peter
P
Liska
Jan
J
Elford
Howard L
HL
Szekeres
Thomas
T
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001550:Benzamidines / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D007939:Leukemia L1210 / Q000188:drug therapy*; D007941:Leukemia P388 / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*
C074761:3,4,5-trihydroxybenzamidoxime; D001550:Benzamidines; D004791:Enzyme Inhibitors; D003520:Cyclophosphamide; D012264:Ribonucleotide Reductases; D002945:Cisplatin