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The Photodamage
of DNA and Protein by Ochratoxin A
Il'ichev, Yuri1,
Perry, Jennifer1 and Simon, John1
DukeUniversity, Durham, NC1
Abstract-
Ochratoxin A (OTA) is a mycotoxin that originates from several species
of Aspergillus and Penicillium fungi and is a common contaminant
of foodstuffs. OTA is nephrotoxic, genotoxic, mutagenic and carcinogenic
in animals. Carcinogenic properties of OTA are also believed to be responsible
for urinary tract cancers in humans affected by the Balkan endemic nephropathy.
The electronic excitation of OTA can result in (1) the cleavage of DNA
and (2) the formation of OTA-protein adducts. This latter observation
provides a photochemical approach for probing the biological activity
of the toxin. The association of OTA with plasma proteins is implicated
as an important component of the mechanism of OTA toxicity. We have
determined binding constants for OTA to components of human plasma.
The experimental conditions have been determined for photochemical producing
the OTA-HSA adduct where the toxin is bound to the protein at its binding
site. Mass spectrometric peptide mapping and sequencing of the OTA labeled
protein provides molecular details of the binding site. This information
provides insights into the molecular mechanism of OTA toxicity as well
as the development of antagonists.
Keywords: mycotoxin,
photo-adduct, ochratoxin A
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