Reactive oxygen species (ROS) is known to be involved in the elaboration of multiple pathologies such as radiation injury, carcinogenesis, aging and atherosclerosis. ROS damages the cell by interacting with critical macromolecules such as DNA, proteins and lipids leading to cell death, mutation and other toxicities. The cellular redox status during normal homeostasis is maintained by a tight balance between the rates of ROS production and their degradation/scavenging..

A state of oxidative stress can be induced by a number of factors, including chemical agents and radiation which results in interruption of redox balance. The stimulation of differences in level of ROS (low to high) in the cells results in varied cellular responses. DNA damage by ROS is well characterized and well studied. Specifically, high doses of ROS are toxic to DNA while low and subtoxic concentration of ROS, damages the DNA and alters various cellular functions which may results in tumor development with mutated DNA, aging or senescence. DNA damage and repair response to high doses are clearly established while response effects of low doses of ROS remains unclear.

In order to define DNA damage dose response and the signal transduction pathways involved in mild oxidative stress and identify the molecular mechanisms of the low oxidative stress, we are in the process of constructing a mathematical model to study the dynamics of Iron dependent DNA damage and repair. This work is being done in collaboration with A/P Marie-Veronique Clement's group from Department of Biochemistry, National University of Singapore.