HPLC determination of binding of cisplatin to DNA in the presence of biological thiols: implications of dominant platinum-thiol binding to its anticancer action.

Purpose: The purpose of this work is to evaluate the extent of the binding of cisplatin (cis-diamminedichloroplatinum(II)) to DNA in the presence and absence of biological thiols, glutathione, and cysteine, and to test the hypothesis whether the platinum-thiol complexes can serve as a drug reservoir for subsequent binding to DNA.

Methods: Reactions of cisplatin (50 microM to 1.0 mM) with calf thymus DNA (870 microM to 6.