Characterization of DNA damage formed upon photoactivation of daunomycin

CHED 1325

Priyanka Kainthla, kainthlr@southwestern.edu, Radhika Kainthla, kainthlr@southwestern.edu, and Maha Zewail-Foote, footezm@southwestern.edu. Department of Chemistry and Biochemistry, Southwestern University, 1001 E. University, Georgetown, TX 78626
Daunomycin, a DNA intercalator, is a potent anthracycline antitumor drug used to treat different forms of leukemia. Photoirradiation leads to the formation of guanine cation radical and daunomycin anion radical, which can subsequently reduce molecular oxygen producing superoxide radical. This photogenerated superoxide radical anion is a precursor to various reactive oxygen species (ROS). Characterizing the types of damage under specific reaction conditions can provide insight into the pathway responsible for damage, either from the formation of guanine radical cation or ROS. In order to quantitatively assess the general types of DNA damage that occur upon photoactivation of daunomycin, we used agarose gel electrophoresis to monitor the topology of supercoiled DNA to closed circular. DNA damage profiles were obtained using repair endonucleases specific for oxidative modifications. Our results show that irradiation of daunomycin leads to single strand breaks, oxidized purine residues, and abasic sites while modified pyrimidine bases were not detected.
 

Undergraduate Research Poster Session: Medicinal
2:00 PM-4:00 PM, Monday, March 26, 2007 Hyatt Regency Chicago -- Riverside Center, Poster

Division of Chemical Education

The 233rd ACS National Meeting, Chicago, IL, March 25-29, 2007