DNA and RNA damage by Cu(II)-amikacin complex.
The oxidation-promoting reactivity of copper(II) complex of aminoglycosidic antibiotic amikacin [Cu(II)-Ami] in the presence of hydrogen peroxide, was studied at pH 7.4, using 2'-deoxyguanosine (dG), pBR322 plasmid DNA and yeast tRNAPhe as target molecules. The mixtures of complex with H2O2 were found to be efficient oxidants, converting dG to its 8-oxo derivative, generating strand breaks in plasmid DNA and multiple cleavages in tRNAPhe. The complex underwent autooxidation as well, with amikacin hydroperoxides as likely major products. This reactivity pattern was found to be due to a combination of metal-bound and free hydroxyl radicals.
Jezowska-Bojczuk
Małgorzata
M
Faculty of Chemistry, University of Wrocław, Wrocław, Poland; Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland. MJB@wchuwr.chem.uni.wroc.pl
Szczepanik
Wojciech
W
Leśniak
Wojciech
W
Ciesiołka
Jerzy
J
Wrzesiński
Jan
J
Bal
Wojciech
W
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000583:Amikacin / Q000494:pharmacology*; D001483:Base Sequence; D003300:Copper / Q000494:pharmacology*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004587:Electrophoresis, Agar Gel; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D013058:Mass Spectrometry; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010100:Oxygen / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D012313:RNA / Q000737:chemistry*; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D013997:Time Factors
D012346:RNA, Transfer, Amino Acyl; D012313:RNA; D003300:Copper; D000583:Amikacin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006861:Hydrogen Peroxide; D003849:Deoxyguanosine; D010100:Oxygen