Stoichiometric preference in copper-promoted oxidative DNA damage by ochratoxin A.
Journal Article (Journal Article)
The ability of the fungal carcinogen, ochratoxin A (OTA, 1), to facilitate copper-promoted oxidative DNA damage has been assessed using supercoiled plasmid DNA (Form I)-agarose gel electrophoresis and gas chromatography-mass spectrometry with selected-ion monitoring (GC-MS-SIM). OTA is shown to promote oxidative cleavage of Form I DNA with optimal cleavage efficiency occurring under excess Cu(II) conditions. As the concentration of OTA was increased and present in excess of Cu(II) the cleavage was less effective. Parallel findings were found for the ability of the OTA-Cu mixture to facilitate oxidative base damage. Yields (lesions per 10(6) DNA bases) of modified bases upon exposure of calf-thymus DNA (CT-DNA) to OTA-H(2)O(2)-Cu(II) were diminished when the OTA:Cu ratio was increased to 5:1. Electrochemical studies carried out in methanol implicate a ligand-centered 2e oxidation of OTA in the presence of excess Cu(II), while product analyses utilizing electrospray mass spectrometry support the intermediacy of the quinone, OTQ (3), in Cu-promoted oxidation of OTA. The implications of these findings with regard to the mutagenicity of OTA are discussed.
- Manderville, RA; Wade Calcutt, M; Dai, J; Park, G; Gillman, IG; Noftle, RE; Mohammed, AK; Birincioglu, M; Dizdaroglu, M; Rodriguez, H; Akman, SA
- June 1, 2003
Volume / Issue
- 95 / 2-3
Start / End Page
- 87 - 96
International Standard Serial Number (ISSN)
Digital Object Identifier (DOI)
- United States