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Influence of Carbonate on the Binding of Carboplatin to DNA
Author(s) -
Sorokanich Robert S.,
Di Pasqua Anthony J.,
Geier Martina,
Dabrowiak James C.
Publication year - 2008
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200890142
Subject(s) - carboplatin , chemistry , dna , cisplatin , agarose gel electrophoresis , hepes , carbonate , microbiology and biotechnology , biochemistry , stereochemistry , organic chemistry , genetics , biology , chemotherapy
The reaction of aged carboplatin (reaction of carboplatin in 24 m M NaHCO 3 for 45 h, 37°, pH 8.6) with pBR322 DNA at 0< r <2.8, where r =[drug]/[DNA‐bp], in 24 m M HEPES buffer, pH 7.4, for 24 h, followed by agarose gel electrophoresis showed DNA mobility changes consistent with unwinding closed circular DNA. However, identical experiments conducted in a two‐buffer system, 24 m M HEPES plus 24 m M carbonate, showed no DNA mobility changes, indicating that carbonate blocks formation of the 1,2 intrastrand cross‐link on DNA. Studies with aged carboplatin and with cisplatin carried out with ca. 4.0< r <10.0 in the two‐buffer system show that some DNA binding and unwinding occurs for both drugs. Since carbonate inhibits the binding of aged carboplatin and cisplatin to DNA, carbonate present in the body likely modulates the reactivity of these drugs with a variety of biological targets including DNA.