DNA cleavage induced by photoactivated daunomycin and the role of reactive oxygen species

CHED 1301

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
Photoexcitation of daunomycin, a widely used anthracycline antitumor agent, can lead to a transfer of an electron from guanine to the drug, forming an anthracycline radical anion. Under aerobic conditions, the electron is transferred to molecular oxygen forming superoxide radical, which can be ultimately converted to DNA reactive oxygen species (ROS). Here, we examine the molecular mechanisms involved in DNA damage of photoactivated daunomycin and the role of dioxygen in this process. A plasmid relaxation assay is used to compare the level of DNA strand breaks that results from spontaneous DNA cleavage in the presence and absence of various ROS scavengers. Photoactivation leads to the conversion of supercoiled DNA to nicked DNA in a time and dose dependent manner and the extent of strand scission depends on the scavenger. These results suggest that ROS may be involved in the formation of spontaneous strand breaks induced by photoactivated daunomycin.
 

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