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pubmed:abstractText |
To elucidate the mechanisms of inactivation of cis-diamminedichloroplatinum(II) (DDP) toxicity by its antidote sodium thiosulfate (STS), we studied the effects of STS on plasma concentrations of platinum (Pt) in vivo, binding of Pt to serum protein in vitro, and uptake of Pt by bacterial cells (E. coli, WP 2 uvrA strain) or cultured mouse tumor cells (FM3A) in vitro. STS did not significantly affect either plasma levels of total Pt or non-protein-bound Pt in vivo, but did inhibit binding of Pt to serum protein and cellular uptake of Pt in vitro. These results suggest that when DDP is given in combination with STS in vivo, the binding to macromolecules and entry of DDP into the cells are prevented due to formation of the Pt-thiosulfate complex in the extracellular fluid.
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