Excretion kinetics of the DNA adducts of cis-diamminedichloroplatinum(II) formed in vitro in rat urine.
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.
Försti
A
A
Institute of Occupational Health, Helsinki, Finland.
Takala
M
M
Laatikainen
R
R
Hemminki
K
K
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002945:Cisplatin / Q000493:pharmacokinetics / Q000652:urine*; D004247:DNA / Q000652:urine*; D003848:Deoxyguanine Nucleotides / Q000302:isolation & purification / Q000652:urine*; D004355:Drug Stability; D007700:Kinetics; D008297:Male; D009944:Organoplatinum Compounds / Q000302:isolation & purification / Q000652:urine*; D051381:Rats; D011919:Rats, Inbred Strains
D003848:Deoxyguanine Nucleotides; D009944:Organoplatinum Compounds; C045231:diammine(2'-deoxyguanylyl-(5'-3')-2'-deoxy-5'-guanylyl)platinate; D004247:DNA; D002945:Cisplatin