A COMPARATIVE-STUDY OF THE CYTO-TOXICITY AND DNA-DAMAGING EFFECTS OF CIS-(DIAMMINO)(1,1-CYCLOBUTANEDICARBOXYLATO)-PLATINUM(II) AND CIS-DIAMMINEDICHLOROPLATINUM(II) ON L1210 CELLS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (9) , 4043-4047
Abstract
Utilizing the DNA alkaline elution technique the DNA lesions produced in L1210 cells after a 2 h exposure to the antitumor agents, cis-(diammino) (1,1-cyclobutanedicarboxylato)-platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (DDP) were compared qualitatively and quantitatively. DNA-protein and DNA interstrand crosslinks are formed in cells exposed to either CBDCA or DDP. In comparison to DDP peak levels of these lesions occur 6 to 12 h later in CBDCA treated cells. Cytotoxicity studies reveal that CBDCA is 45 times less potent than DDP to L1210 cells when compared on a molar basis. The decreased cytotoxicity of CBDCA and the 12 h delay in peak cross-linking when compared to DDP is interpreted as a decreased reactivity of the intact CBDCA towards the DNA. This decreased reactivity may be due in part to the presence of a stable bidentate dicarboxylate chelate ring structure of CBDCA resulting in a much slower rate of hydrolysis to the active form of the drug.