PMID: 3768295Aug 12, 1986Paper

Chemical reactivity of monofunctional platinum-DNA adducts

Biochemistry
J L Butour, N P Johnson

Abstract

Complexes formed in vitro between cis- or trans-PtCl2(NH3)2 (DDP) and DNA were found to contain monofunctional adducts that reacted with exogenous guanosine. [14C]Guo bound irreversibly to cis- and trans-DDP-DNA complexes to form bis-Gua adducts. The reaction was first order with respect to the concentration of both [14C]Guo and platinum-DNA complex, but the rate of the reaction varied nonlinearly as a function of the level of platinum binding on DNA. The reaction between [14C]Guo and these platinum-DNA complexes was used to probe the concentration and stability of the monofunctional adducts and to investigate their chemistry in situ. The concentration of monofunctional adducts was highest immediately after reaction of DDP with DNA for 2 h at 37 degrees C, at which time they represented greater than 15% of the cis-DDP-DNA lesions and on the order of 80% of the trans-DDP-DNA lesions. The cis-DDP-DNA complex reacted with [14C]Guo by two kinetically distinct processes, indicating two types of reactive adducts. The most reactive adduct represented 5% of the platinum lesions. These monofunctional adducts disappeared during the incubation of the platinum-DNA complexes in the absence of drug, probably as a result of chelation to DNA. ...Continue Reading

Citations

Apr 1, 1988·Cancer Metastasis Reviews·P C Hydes, M J Russell
Oct 5, 2011·Cancer Chemotherapy and Pharmacology·C L KingM Barbier
Jul 23, 1991·Biochimica Et Biophysica Acta·J Hayes, W M Scovell
Sep 21, 2000·Journal of Chromatography. B, Biomedical Sciences and Applications·A ZenkerW Lindner
Dec 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·W I SundquistB D Stollar
Aug 15, 1993·European Journal of Biochemistry·V Brabec, Z Balcarova
Nov 30, 1992·Biochemical and Biophysical Research Communications·K BouayadiB Salles
May 29, 2000·Chemico-biological Interactions·L R FergusonD R Phillips

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