Document Type

Article

Date

7-2006

Embargo Period

4-29-2013

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.

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

Source

local input

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.

Included in

Chemistry Commons

Share

COinS