The marsupial Monodelphis domestica represents a novel animal model with which to study the role of a specific ultraviolet radiation (UVR)-induced, DNA lesion in the photobiology of mammalian skin. As in humans, cells in the epidermis of M. domestica have a high capacity for the photoreactivation (PR) of UVR-induced pyrimidine dimers. This light-dependent, repair pathway has the unique property of acting only on pyrimidine dimers and if PR decreases the ability of UVR to induce a photobiological response it is definitive evidence that pyrimidine dimers are involved in the induction of that response. The ability to correlate UVR-induced molecular lesions with photobiological responses of the skin will contribute valuable information to the field of dermatology, especially those areas involved with pathological conditions of the skin. The long-term objective of this project is to use the PR capacity present in cells of marsupial skin to study the role, and possible site of action, of UVR-induced pyrimidine dimers in photobiological responses of mammalian skin.
The specific aims are: 1) determine action spectra for the induction of pyrimidine dimers in dermal and in epidermal DNA. A concordance between one of these action spectra with an action spectrum for induction of phototoxic reactions will be indicative of the site (dermal vs. epidermal) of induction of phototoxicity; 2) determine optimal conditions for the photoreversal of pyrimidine dimers in the epidermal DNA of M. domestica; 3) use PR to determine the role of pyrimidine dimers in UVR-induced pertubations of cell cycle kinetics and histopathological changes in mammalian skin; 4) carry out split treatment studies in which the UVR exposure is separated from the PR treatment by increasing periods of time. The kinetics of the decay in the ability to photoreactivate the induction of a phototoxic reaction may be indicative of the kinds of early reactions that occur in the expression of phototoxic events.
