REACTIVE OXYGEN SPECIES AND ULTRAVIOLET LIGHT DAMAGE

CHEMEX PHARMACEUTICALS, INC.'S, NORDIHYDROGUAIARETIC ACID (CHX 100) IS A POTENT ANTIOXIDANT ALSO POSSESSING ANTIPROLIFERATIVE, ANTITUMOR, AND LIPOXYGENASE INHIBITION ACTIVITIES. THESE ACTIONS, ESPECIALLY ITS ANTIOXIDANT AND LIPOXYGENASE INHIBITORY ACTIVITIES, SUGGEST THAT CHX 100 MAY REDUCE THE DELETERIOUS EFFECTS OF ACUTE ULTRAVIOLET LIGHT (UVL) EXPOSURE ON THE SKIN, AS THESE EFFECTS MAY BE ASSOCIATED WITH FORMATION OF REACTIVE OXYGEN SPECIES (ROS). SUCH EFFECTS INCLUDE ERYTHEMA, EDEMA, AND DAMAGE TO THE EPIDERMAL KERATINOCYTE AND MELANOCYTE. IN ADDITION, THE REPORTED ABILITY OF CHX 100 TO ATTENUATE TUMOR DEVELOPMENT IN A MURINE MODEL OF SKIN TUMOR INITIATIONAND PROMOTION SUGGESTS THE DRUG COULD PREVENT SOME OF THE DELETERIOUS EFFECTS OF CHRONIC SUN EXPOSURE, SUCH AS THE DEVELOPMENT OF PRECANCEROUS AND CANCEROUS LESIONS. THE GOAL OF THIS STUDY IS TO EVALUATE THE ROLE OF ROS IN UVL-INDUCED DAMAGE TO SKIN CELLS AND THE ABILITY OF CHX 100 AND ROS SCAVENGERS TO PREVENT THIS DAMAGE. THE SPECIFIC AIMS ARE TO DETERMINE: (1) THE EFFECTS OF UVL ON ARACHIDONIC ACID RELEASE FROM, AND VIABILITY OF, CULTURED HUMAN KERATINOCYTES AND THE ABILITY OF CHX 100 AND ROS SCAVENGERS TO ALTER THIS RESPONSE; AND (2) THE ABILITY OF CHX 100 AND ROS SCAVENGERS TO ATTENUATE UVL-INDUCED MELANOCYTE HYPERPLASIA AND HYPERPIGMENTATION.