Complexion coloration is essential to ones health, self-image, and thus overall wellness, both physically and psychologically. Cutaneous pigmentation protects a person from various environmental assaults, like ultraviolet light, as well as potential cellular injury, that can cause cancer and aging of the skin. Loss of skin pigmentation can result in cancer, aging, and compromised immunity of the skin as well as psychological and social problems of self- esteem and personal interactions. Occupational/contact vitiligo is a disease that results in the loss of cutaneous pigmentation. This form of vitiligo occurs relatively frequently in individuals exposed to phenolic/catecholic derivatives primarily in the work place. This disease can be financially and socially devastating for the individual, in addition to it compromising the productivity in the workplace. The general goal of this proposal is to assess the pathological effects of phenolic and catecholic derivatives on melanocytes. These prevalent chemical toxins are responsible for the development of occupational/contact vitiligo in the skin of some individuals exposed to these environmental agents in the workplace. Specifically, we propose to assess the relative cytotoxicity, the interaction with tyrosinase, and the generation of toxic free radical products within melanocytes exposed to various phenolic and catecholic derivatives. In this assessment, we will determine whether melanocytes from all patients with vitiligo, patients with the occupational/contact form of vitiligo, family members of patients with vitiligo, and/or a subset of the population in general, are more sensitive to cytotoxicity by these phenolic/catecholic derivatives. In addition, we will assess [1] genes that are differentially expressed and [2] regulators of apoptosis in cells treated with phenolic/catecholic derivatives. In addition, we will determine whether the response of these molecules is altered in vitiligo melanocytes demonstrated to be more susceptible to cytotoxicity. Finally, we will assess the effectiveness of various antioxidants, especially catalase, in dampening the cytotoxic effect of phenolic/catecholic derivatives using cultured melanocytes, organotypic cultures of human skin, and a guinea pig model.
