Influence of carbonate on the binding of carboplatin to DNA.
The reaction of aged carboplatin (reaction of carboplatin in 24 mM NaHCO(3) for 45 h, 37 degrees, pH 8.6) with pBR322 DNA at 0 < r < 2.8, where r = [drug]/[DNA-bp], in 24 mM 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 mM HEPES plus 24 mM 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.
Sorokanich
Robert S
RS
Department of Chemistry, Syracuse University, 111 College Place, Rm 1-014 CST, Syracuse, NY 13244-4100, USA (phone: +1-315-443-4601; fax: +1-315-443-4070).
Di Pasqua
Anthony J
AJ
Department of Chemistry, Syracuse University, 111 College Place, Rm 1-014 CST, Syracuse, NY 13244-4100, USA (phone: +1-315-443-4601; fax: +1-315-443-4070).
Geier
Martina
M
Department of Chemistry, Syracuse University, 111 College Place, Rm 1-014 CST, Syracuse, NY 13244-4100, USA (phone: +1-315-443-4601; fax: +1-315-443-4070).
Dabrowiak
James C
JC
Department of Chemistry, Syracuse University, 111 College Place, Rm 1-014 CST, Syracuse, NY 13244-4100, USA (phone: +1-315-443-4601; fax: +1-315-443-4070).
D001665:Binding Sites; D016190:Carboplatin / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D004587:Electrophoresis, Agar Gel; D017693:Sodium Bicarbonate / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D017693:Sodium Bicarbonate; D004247:DNA; D016190:Carboplatin