Evaluation of trans-tetrachloro-1,2-diaminocyclohexane platinum (IV) in murine leukemia L1210 resistant and sensitive to cis-diamminedichloroplatinum (II).
trans-Tetrachloro-1,2-diaminocyclohexane platinum (IV) (tetraplatin) was therapeutically effective in mice bearing leukemia L1210 resistant (L1210/DDPt) or sensitive (L1210/0) to cis-diamminedichloroplatinum (II) (cisplatin). Furthermore, the sensitivity of cultured L1210/DDPt and L1210/0 cell populations to tetraplatin, cisplatin, and dichloro-trans-dihydroxyisopropylamine platinum (IV) (CHIP) was a function of the concentrations used for each compound. The relative degree of sensitivity between cultured L1210/DDPt and L1210/0 cells for each compound on the basis of the LC99 (the concentration of each compound required to reduce the number of viable cells by 99% in each cell line) was 3-fold for cisplatin, 2-fold for tetraplatin, and 3-fold for CHIP; thus the cultured L1210/0 cells exhibited a greater degree of sensitivity than the L1210/DDPt cells to the platinum compounds. The data indicate that if reduction of platinum IV compounds to platinum II compounds or metabolites is required for antitumor activity, then the cultured L1210 cells are capable of this bioreduction independently of any host factors.
Wilkoff
L J
LJ
Kettering-Meyer Laboratory, Southern Research Institute, Birmingham, AL 35255-5305.
Dulmadge
E A
EA
Trader
M W
MW
Harrison
S D
SD
Griswold
D P
DP
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002452:Cell Count; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D009944:Organoplatinum Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D002945:Cisplatin; C049777:ormaplatin