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

Abstract
The main adduct of cis -diamminedichloroplatinum(ll) ( cis -Pt) with DNA, cis -[Pt(NH 3 ) 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 the chemical instability of cis -[Pt(NH 32 (dGpdG)] in urine as shown in an in vitro incubation. Adjusted for this instability the recovery in urine was > 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(NH 3 ) 2 (dGpdG)] and cis -[Pt(NH 3 ) 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.

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