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A Comparative Study of the Cytotoxicity and DNA-damaging Effects of cis-(Diammino)(1,1-cyclobutanedicarboxylato)-platinum(II) and cis-Diamminedichloroplatinum(II) on L1210 Cells

Laboratory of Cell Biology and Pharmacology, Section of Hematology-Oncology, Department of Medicine, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois 60153

Utilizing the DNA alkaline elution technique we have compared qualitatively and quantitatively 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). DNA-protein and DNA interstrand cross-links are formed in cells exposed to either CBDCA or DDP. However, 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.

¹ To whom requests for reprints should be addressed, at 2160 South First Avenue, Maywood, IL 60153.

Received 2/18/85. Revised 5/ 6/85. Accepted 6/ 6/85.

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