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The synergistic lethal interaction of Cis-diamminedichloroplatinum and natural nucleosides is related to increased DNA cross-links

1985; Elsevier BV; Volume: 55; Linguagem: Inglês

10.1016/s0009-2797(85)80116-2

1872-7786

Benjamin Drewinko, M.A. Dipasquale, Liying Yang, Barthel Barlogie, José M. Trujillo,

Advanced biosensing and bioanalysis techniques

Human tumor cells were treated in vitro with combinations of cis- or trans-dichlodiammineplatinum (DDP) and natural nucleosides (thymidine, uridine, cytidine and adenosine). Effects were measured by inhibition of colony-formation (cell survival) and DNA alkaline elution (DNA cross-links). No increments in cell lethality or DNA cross-links were elicited by any combination of trans-DDP and nucleosides. In contrast, every combination of cis-DDP and nucleoside was eminently synergistic with 5- and 10-fold increases in cell lethality over the predicted sum of each agent alone. These increments in cell kill correlated linearly with increases in DNA crosslinks suggesting that the nucleosides interact with cis-DDP to enhance its cytotoxic crosslinking mode of action.