TY - JOUR
T1 - Oxidative DNA damage following photoexcitation of daunomycin
T2 - Direct role of oxygen
AU - Kainthla, Radhika
AU - Zewail-Foote, Maha
N1 - Funding Information:
We express thanks to Dr. Lynn Guziec (Southwestern University) for assistance with the anaerobic process and Dr. Sandra Loudwig (Southwestern University) and Dr. Stony Lo (The University of Texas at Austin) for assistance and helpful comments. We thank the Robert A. Welch Foundation (AF-0005) for financial support and acknowledgement is made to the Donors of the American Chemical Society Petroleum Research Fund for support of this research.
PY - 2008/8/15
Y1 - 2008/8/15
N2 - The chemistry of the photoactivation of daunomycin-DNA complexes is reported and the mechanism is elucidated. We quantitatively assessed the type of DNA damage, such as strand breaks, oxidized bases, and abasic sites, that arise using a plasmid relaxation assay coupled with DNA repair endonucleases. Photoexcitation of daunomycin leads to oxidative DNA damage in a dose- and irradiation time-dependent manner and guanine-specific oxidized purines are substantially produced under these conditions. Oxidative DNA base damage was also inhibited by argon degassing, indicating that guanine-specific damage arises from an oxygen-dependent mechanism. In addition, photoexcitation of daunomycin-DNA complexes leads to superoxide anion radical formation. From these studies of the actual product formed, we conclude that a charge transfer is a main driving force of the mechanism.
AB - The chemistry of the photoactivation of daunomycin-DNA complexes is reported and the mechanism is elucidated. We quantitatively assessed the type of DNA damage, such as strand breaks, oxidized bases, and abasic sites, that arise using a plasmid relaxation assay coupled with DNA repair endonucleases. Photoexcitation of daunomycin leads to oxidative DNA damage in a dose- and irradiation time-dependent manner and guanine-specific oxidized purines are substantially produced under these conditions. Oxidative DNA base damage was also inhibited by argon degassing, indicating that guanine-specific damage arises from an oxygen-dependent mechanism. In addition, photoexcitation of daunomycin-DNA complexes leads to superoxide anion radical formation. From these studies of the actual product formed, we conclude that a charge transfer is a main driving force of the mechanism.
KW - Charge transfer reactions
KW - DNA damage
KW - Daunomycin
KW - Photochemistry
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U2 - 10.1016/j.jphotochem.2008.03.009
DO - 10.1016/j.jphotochem.2008.03.009
M3 - Article
AN - SCOPUS:44649136894
VL - 198
SP - 200
EP - 204
JO - Journal of Photochemistry and Photobiology A: Chemistry
JF - Journal of Photochemistry and Photobiology A: Chemistry
SN - 1010-6030
IS - 2-3
ER -