Date of Graduation


Document Type


Degree Type



School of Medicine


Physiology, Pharmacology & Neuroscience

Committee Chair

Anna A. Shvedova.


Free radicals threaten various tissues and are involved in the development and progression of many pathological states and diseases. More than other tissues, the skin is exposed to a variety of chemical, environmental, and physical agents which are capable of inducing radical formation resulting in the development of oxidative stress. The skin possesses an elaborate antioxidant network to deal with reactive oxygen species (ROS); however, excessive exposure and/or radical production can overwhelm the antioxidant capabilities of the skin causing oxidative damage to proteins, DNA, and lipids. The central hypothesis of these studies is that exposure to oxidizible chemicals and/or environmental agents to skin are able to induce free radical formation with subsequent antioxidant reduction, oxidative DNA, lipid and protein damage, and inflammation. Excessive inflammatory-based oxidative modification of the major skin constituents following long-term exposure could trigger redox-sensitive cell-signaling pathways via activator protein 1 (AP-1) expression thereby causing the development of skin cancer. The specific aims of the project are: (1) To study the mechanisms of phenol (PhOH)-induced oxidative injury in skin of animals with normal and reduced antioxidant milieu; (2) To assess the role of the antioxidant defense system of the skin of young and old mice exposed to cumene hydroperoxide (Cum-OOH); (3) To investigate the role of oxidative stress and the activation of AP-1 protein in the development of skin cancer; (4) To study the mechanisms of simulated solar light (SSL) induced skin injury with respect to antioxidant imbalance, oxidative damage of DNA, protein, and lipids. Results obtained from these studies provide critical knowledge about the mechanisms of dermal toxicity of phenolic compounds, organic peroxides and UV light with regard to reactive oxygen intermediates formed in skin. The efficiency of the antioxidant network is essential to withstand an oxidative skin injury due to aging, occupational and environmental exposures.