ATP, histidine or magnesium ions can protect DNA against sisomicin-induced damage, following stray Cu(II) binding.
The oxidative DNA damage by the cupric complexes of sisomicin was investigated in the presence of varying amounts of histidine, ATP, Mg(II) ions or phosphates. We found that by very low concentrations, the amino acid is able to inhibit the cleavage totally. This occurs both by its competition with antibiotic for copper(II) binding, what was proved by spectroscopic measurements, as well as by ROS scavenging by the imidazole ring. ATP and magnesium also exert an influence on the yield of the DNA destruction by decreasing the amount of the single strand breaks, however only their significant excess is able to break this process. The influence of ATP on the plasmid damage has in this case a similar chemical mechanism to that one observed for histidine. Mg(II) ions, however, interact with DNA and thus prevent the complex binding. Only phosphate anions, in the range of their physiological concentrations, exert no influence on the cleavage process.
Szczepanik
Wojciech
W
Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland.
Swiatek
Magdalena
M
Skała
Jacek
J
Jezowska-Bojczuk
Małgorzata
M
D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002942:Circular Dichroism; D003300:Copper / Q000378:metabolism*; D004247:DNA / Q000187:drug effects* / Q000378:metabolism*; D006639:Histidine / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D012853:Sisomicin / Q000737:chemistry / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D010710:Phosphates; D006639:Histidine; D003300:Copper; D000255:Adenosine Triphosphate; D004247:DNA; D008274:Magnesium; D012853:Sisomicin