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Stoichiometric Preference in Copper-Promoted Oxidative DNA Damage by Ochratoxin A

Published

Author(s)

R A. Manderville, W M. Calcutt, J Dai, G Park, I G. Gillman, R E. Noftle, A K. Mohammed, M. Dizdaroglu, H Rodriguez, S A. Akman

Abstract

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 (nmol/mg of DNA) of modified bases upon exposure of calf-thymus DNA (CT-DNA) to OTA/H2O2/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.
Citation
Journal of Inorganic Biochemistry
Volume
97
Issue
No. 2

Keywords

8-hydroxyguanine, carcinogenesis, food additives, formamidopyrimidines, oxidative DNA damage, oxidative stress

Citation

Manderville, R. , Calcutt, W. , Dai, J. , Park, G. , Gillman, I. , Noftle, R. , Mohammed, A. , Dizdaroglu, M. , Rodriguez, H. and Akman, S. (2003), Stoichiometric Preference in Copper-Promoted Oxidative DNA Damage by Ochratoxin A, Journal of Inorganic Biochemistry (Accessed April 14, 2024)
Created September 30, 2003, Updated October 12, 2021