Discrepancy between cytotoxicity and DNA interstrand crosslinking of carboplatin and cisplatin in vivo.
We used the method of alkaline elution to compare quantitatively the DNA lesions produced by cisplatin and carboplatin in the AKR leukemia in vivo. These data were compared with cytotoxicity of each drug in the same animal model and in a solid tumor murine model (colon 26). DNA-protein and DNA-DNA interstrand crosslinks were formed in similar proportions by both drugs when peak values of crosslinking were compared. No clear difference in the rate of formation of both types of crosslinks could be observed between these drugs. On a molar basis a 3- to 4-fold more carboplatin had to be given to obtain equivalent frequencies of both types of crosslinks. In contrast, to obtain equitoxicity in the same animal tumor model, 13 fold higher doses of carboplatin had to be given. This difference in cytotoxicity between both drugs is comparable to the difference measured in colon 26 in vivo (16 fold). Both values are in the range of literature data (10-25 fold) dealing with the relative potency of cisplatin and carboplatin in murine tumor models.
DeNeve
W
W
Wayne State University School of Medicine, Department of Internal Medicine, Detroit, MI 48201.
Valeriote
F
F
Tapazoglou
E
E
Everett
C
C
Khatana
A
A
Corbett
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000032:analysis / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D007942:Leukemia, Experimental / Q000188:drug therapy; D051379:Mice; D008806:Mice, Inbred AKR; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D013154:Spleen / Q000032:analysis
D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D004273:DNA, Neoplasm; D009944:Organoplatinum Compounds; D016190:Carboplatin; D002945:Cisplatin