Document Type
Article
Date
7-2006
Keywords
Cisplatin, Monofunctional, Carbonate, Supercoiled DNA, Binding
Disciplines
Chemistry
Description/Abstract
Carbonate in its various forms is an important component in blood and the cytosol. Since, under conditions that simulate therapy, carbonate reacts with cisplatin to form carbonato complexes, one of which is taken up and/or modified by the cell [C.R. Centerwall, J. Goodisman, D.J. Kerwood, J. Am. Chem. Soc., 127 (2005) 12768–12769], cisplatin-carbonato complexes may be important in the mechanism of action of cisplatin. In this report we study the binding of cisplatin to pBR322 DNA in two different buffers, using gel electrophoresis. In 23.8 mM HEPES, N-(2-hydroxyethyl)-piperazine-N′-2-ethanesulfonic acid, 5 mM NaCl, pH 7.4 buffer, cisplatin produces aquated species, which react with DNA to unwind supercoiled Form I DNA, increasing its mobility, and reducing the binding of ethidium to DNA. This behavior is consistent with the formation of the well-known intrastrand crosslink on DNA. In 23.8 mM carbonate buffer, 5 mM NaCl, pH 7.4, cisplatin forms carbonato species that produce DNA-adducts which do not significantly change supercoiling but enhance binding of ethidium to DNA. This behavior is consistent with the formation of a monofunctional cisplatin adduct on DNA. These results show that aquated cisplatin and carbonato complexes of cisplatin produce different types of lesions on DNA and they underscore the importance of carrying out binding studies with cisplatin and DNA using conditions that approximate those found in the cell.
Recommended Citation
Binter, Alexandra; Goodisman, Jerry; and Dabrowiak, James C., "Formation of monofunctional cisplatin-DNA adducts in carbonate buffer" (2006). Chemistry - All Scholarship. 89.
https://surface.syr.edu/che/89
Source
local input
Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.
Additional Information
Copyright 2006 Journal of Inorganic Biochemistry. This article may be downloaded for personal use only. Any other use requires prior permission of the author and Journal of Inorganic Biochemistry.
The article may be found at http://www.sciencedirect.com/science/article/pii/S0162013406000560