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DNA-Protein and DNA Interstrand Cross-linking by cis- and trans- Platinum(II) Diamminedichloride in L1210 Mouse Leukemia Cells and Relation to Cytotoxicity¹

Division of Cancer Treatment, National Cancer Institute, NIH, Bethesda, Maryland 20014

The effects of cis- and trans-platinum(II) diamminedichloride on L1210 cells were investigated using the technique of DNA alkaline elution. Both agents produced reductions in alkaline elution rates which were partially or, in some cases, almost completely reversed by incubation of the cell lysates with proteinase K. The proteinase-sensitive component of this effect is taken to reflect DNA-protein cross-linking, while the proteinase-resistant component of this effect may include interstrand cross-links. The cytotoxicity of the two agents did not correlate with the extent of DNA-protein cross-linking but did appear to correlate with the extent of proteinase-resistant cross-linking; therefore, there may be a relationship between cytotoxicity and interstrand cross-linking.

¹ A portion of this work has appeared in abstract form (41).

² To whom requests for reprints should be addressed, at Medicine Branch, Building 10, Room 12N226, NIH, Bethesda, Md. 20014.

Received 6/16/78. Accepted 10/23/78.