The Biophysics Research
Program at ETSU
Hypoxia-Selective
Modification of Radiation Damage to DNA
DNA has long been recognized as a principal target for ionizing radiation in cells at low doses. Many of the chemical alterations produced by radiation in DNA, if not repaired, result in cell death. The lethal effect of radiation on tumor cells is widely used in radiation cancer treatment. This emphasizes the importance of selective targeting of DNA in these cells since it reduces the overall dose needed to kill the cell.
One of the basic problems associated with radiation cancer treatment is the selective targeting of tumors. The microenvironment of solid tumors has several specific features that distinguish them from that of surrounding normal tissues. One of the most pronounced of them is the tumor hypoxia (reduced oxygenation level) originating from relatively poor vascularization.. Hypoxia decreases radiosensitivity of tumor cells up to 3-fold as compared to well-oxygenated cells, which is an unfavorable situation from the viewpoint of radiation cancer treatment. There is no question nowadays that the treatment outcome, i.e. tumor survival is directly related to its oxygenation level. On the other hand, hypoxia is not only a problem, but also a feature that makes tumor tissues distinguishable from normal ones. This underscores the importance of understanding the mechanisms of radiation-induced DNA damage and of development of the chemical modifiers capable of enhancing radiation damage to cellular DNA selectively in hypoxic areas.
My research is aimed at the development of hypoxia-selective agents for directional modification of DNA upon activation with ionizing radiation. The term “directional” includes both the predictable structure of the generated lesion, and its localization in the target DNA. Specifically, the project focuses on the mechanisms and sequence-specificity of DNA damage by several prospective DNA cleaving agents and their conjugates with established DNA-recognizing entities.
Pictures of Yuri’s Lab
Cary 100 Bio Spectrophotometer
Waters Associates HPLC