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Kinetics of Formation and Disappearance of a DNA Cross-linking Effect in Mouse Leukemia L1210 Cells Treated with cis- and trans-Diamminedichloroplatinum(II)

Laboratory of Molecular Pharmacology [K. W. K., W. E. R., R. A. G. E.], and the Medicine Branch [L. A. Z., T. A.], Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20014

cis- and trans-diamminedichloroplatinum(II) (PDD) produced a DNA cross-linking effect in mouse leukemia L1210 cells, which was demonstrable after subtoxic treatments with the DNA alkaline elution technique. Crosslinking effects developed following treatments with concentrations as low as 1 µM for cis-PDD and 5 µM for trans-PDD, which permitted over 80% survival of colony-forming ability. The maximum cross-linking effect by cis-PDD required about 12 hr of posttreatment incubation before it was fully developed, whereas the cross-linking effect of trans-PDD was fully developed at the end of the 1-hr drug exposure. The cross-linking effects of both agents were reversed upon further incubation of the cells.

Received 7/18/77. Accepted 3/16/78.

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