Continuing depletion of the protective ozone layer of the atmosphere may lead to dramatic increases in human exposure to damaging ultraviolet (UV) radiation. Documented adverse effects of UV exposure in man include immunosuppression and the development of skin tumors. These effects are also seen in the mouse, the most commonly employed animal model for studies of UV effects. In addition, chronic exposure to UV radiation shortens the lifespan of mice in a dose-dependent fashion. This finding suggests that increased environmental UV exposure may also decrease human longevity. In the proposed studies The South American opossum (Monodelphis domestica) will be used to investigate the life-shortening effects of UV radiation. This animal model offers certain advantages over the laboratory mouse. While both man and the opossum share the ability to repair UV-induced pyrimidine dimers by efficient excision repair and photoreactivation (a specific light-dependent enzymatic pathway), mice completely lack photoreactivation capabilities and have relatively inefficient excision repair. In addition, the ability to induce the photoreactivation pathway of the opossum by appropriate exposure to visible light allows correlations to be made between pyrimidine dimer formation in UV-exposed skin and adverse health effect of UV exposure. Those adverse effects which are prevented by post-UV photoreactivation must be initiated by UV-induced dimers, since removal of dimers prevents their development. Preliminary studies in the opossum demonstrate that photoreactivation lessens the severity of the acute skin response to UV exposure, decreases the incidence of skin tumors in animals chronically exposed to UV, and diminishes some immunosuppressive effects of UV. We have preliminary evidence that photoreactivating treatment also partially abrogates the life-shortening effect of chronic UV exposure in opossums. We wish to explore in detail the life-shortening effect of chronic UV exposure. Opossums will be exposed to a life-shortening UV irradiation regime; half of the animals will subsequently be exposed to photoreactivating light. For these animals and for control animals exposed only to photoreactivating light, lifespan, cause of death, and immune status will be determined. Comparison of results for these three groups of animals will indicate the mechanism of the life-shortening effect of UV irradiation and will determine the role of pyrimidine dimer formation in reducing lifespan.
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