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Stoichiometric preference in copper-promoted oxidative DNA damage by ochratoxin A.

Publication ,  Journal Article
Manderville, RA; Wade Calcutt, M; Dai, J; Park, G; Gillman, IG; Noftle, RE; Mohammed, AK; Birincioglu, M; Dizdaroglu, M; Rodriguez, H; Akman, SA
Published in: J Inorg Biochem
June 1, 2003

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.

Published In

J Inorg Biochem

DOI

ISSN

0162-0134

Publication Date

June 1, 2003

Volume

95

Issue

2-3

Start / End Page

87 / 96

Location

United States

Related Subject Headings

  • Spectrophotometry, Ultraviolet
  • Spectrometry, Mass, Electrospray Ionization
  • Plasmids
  • Oxidation-Reduction
  • Ochratoxins
  • Inorganic & Nuclear Chemistry
  • Hydrogen Peroxide
  • Gas Chromatography-Mass Spectrometry
  • Electrophoresis, Agar Gel
  • Electrochemistry
 

Citation

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Manderville, R. A., Wade Calcutt, M., Dai, J., Park, G., Gillman, I. G., Noftle, R. E., … Akman, S. A. (2003). Stoichiometric preference in copper-promoted oxidative DNA damage by ochratoxin A. J Inorg Biochem, 95(2–3), 87–96. https://doi.org/10.1016/s0162-0134(03)00104-1
Manderville, Richard A., M. Wade Calcutt, Jian Dai, Gyungse Park, Ivan G. Gillman, Ronald E. Noftle, Abdul K. Mohammed, et al. “Stoichiometric preference in copper-promoted oxidative DNA damage by ochratoxin A.J Inorg Biochem 95, no. 2–3 (June 1, 2003): 87–96. https://doi.org/10.1016/s0162-0134(03)00104-1.
Manderville RA, Wade Calcutt M, Dai J, Park G, Gillman IG, Noftle RE, et al. Stoichiometric preference in copper-promoted oxidative DNA damage by ochratoxin A. J Inorg Biochem. 2003 Jun 1;95(2–3):87–96.
Manderville, Richard A., et al. “Stoichiometric preference in copper-promoted oxidative DNA damage by ochratoxin A.J Inorg Biochem, vol. 95, no. 2–3, June 2003, pp. 87–96. Pubmed, doi:10.1016/s0162-0134(03)00104-1.
Manderville RA, Wade Calcutt M, Dai J, Park G, Gillman IG, Noftle RE, Mohammed AK, Birincioglu M, Dizdaroglu M, Rodriguez H, Akman SA. Stoichiometric preference in copper-promoted oxidative DNA damage by ochratoxin A. J Inorg Biochem. 2003 Jun 1;95(2–3):87–96.
Journal cover image

Published In

J Inorg Biochem

DOI

ISSN

0162-0134

Publication Date

June 1, 2003

Volume

95

Issue

2-3

Start / End Page

87 / 96

Location

United States

Related Subject Headings

  • Spectrophotometry, Ultraviolet
  • Spectrometry, Mass, Electrospray Ionization
  • Plasmids
  • Oxidation-Reduction
  • Ochratoxins
  • Inorganic & Nuclear Chemistry
  • Hydrogen Peroxide
  • Gas Chromatography-Mass Spectrometry
  • Electrophoresis, Agar Gel
  • Electrochemistry