A simple method for the inactivation of monofunctionally DNA-bound cis-diamminedichloroplatinum (II).
The effects of inorganic salts on the binding of cis-diamminedichloroplatinum(II) (= cis-Pt) to salmon sperm DNA have been investigated for various concentrations of NaCl, NaHCO3, and NH4HCO3. In concentrations of 0.01 M or higher, all three salts strongly inhibit the binding to DNA. However, only NH4HCO3, which may generate NH3, is able to block irreversibly the reactive coordination sites of cis-Pt. This was shown when monofunctionally bound cis-Pt-dGMP was treated with the salts, followed by incubation with an excess of dGMP, after dilution to reduce the salt concentration. The results indicated that monofunctionally bound cis-Pt-dGMP was preserved during the incubation with the excess of dGMP, when NH4HCO3 was used during the pretreatment. Similar treatments with NaCl or NaHCO3, on the other hand, could not prevent the subsequent formation of the bifunctionally bound adduct cis-Pt(NH3)2(dGMP)2. Evidence is given for the formation of Pt(NH3)3dGMP upon treatment of monofunctionally bound cis-Pt-dGMP with NH4HCO3.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D002945:Cisplatin; D004247:DNA; D003848:Deoxyguanine Nucleotides; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D012474:Salmon; D013094:Spermatozoa
D003848:Deoxyguanine Nucleotides; C007257:2'-deoxyguanosine 5'-phosphate; D004247:DNA; D002945:Cisplatin