Excretion kinetics of the DNA adducts of cis-diamminedichloroplatinum(II) formed in vitro in rat urine

Carcinogenesis. 1988 Oct;9(10):1745-8. doi: 10.1093/carcin/9.10.1745.

Abstract

The main adduct of cis-diamminedichloroplatinum(II) (cis-Pt) with DNA, cis-[Pt(NH3)2(dGpdG)], was administered i.p. to rats. Urine was collected daily for 4 days. The adduct was purified by a weak cation exchanger and quantitated by HPLC with UV detection. The recovery of the adduct was 30.0 +/- 7.0% (mean +/- SEM). The main reason for the low recovery was the chemical instability of cis-[Pt(NH3)2 (dGpdG)] in urine as shown in an in vitro incubation. Adjusted for this instability the recovery in urine was greater than 70% of the dose. When cis-Pt-DNA (the molar ratio of cis-Pt to nucleotide = 1:50) was administered i.p. to rats only 1.25 +/- 0.23% of platinum was excreted in urine in the form of cis-[Pt(NH3)2(dGpdG)] and cis-[Pt(NH3)2(dApdG)] during the first 4 days. If the removal of the cis-Pt-DNA adducts from human tissues is to be followed, their possible slow excretion and chemical instability in urine needs to be considered.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • Cisplatin / pharmacokinetics
  • Cisplatin / urine*
  • DNA / urine*
  • Deoxyguanine Nucleotides / isolation & purification
  • Deoxyguanine Nucleotides / urine*
  • Drug Stability
  • Kinetics
  • Male
  • Organoplatinum Compounds / isolation & purification
  • Organoplatinum Compounds / urine*
  • Rats
  • Rats, Inbred Strains

Substances

  • Deoxyguanine Nucleotides
  • Organoplatinum Compounds
  • diammine(2'-deoxyguanylyl-(5'-3')-2'-deoxy-5'-guanylyl)platinate
  • DNA
  • Cisplatin