Objective
The incidence of all types of skin cancer has risen within Europe over the last three decades. This is seen as a consequence of increased exposure to sunlight, a situation which will become exacerbated on increased exposure to UVB as a result of depletion of the ozone layer. Six well found laboratories will combine their unique expertise in an effort to provide information to assist in reversing or halting this trend.
The proposal is intended as a continuation of an existing highly successful collaboration (EVSV CT9 1- 0034 ) whose aim is to obtain a proper understanding of the fundamental mechanisms underlying the biological effects of human exposure to UVB and sunlight. We will provide information on the activity of UVB in the initiation step ( via lethality, clastogenicity and mutability ) and the promotional step (via immunomodulation and altered gene expression) of carcinogenesis. We will concentrate our studies on the in vitro response of cells derived from human skin to calibrated UVB sources and natural sunlight. Subsequent studies will attempt to corroborate laboratory results with investigations on intact skin samples and ultimately on human volunteers. Our experimental approach is based upon procedures which have proved successful in our present collaboration: (1) We will characterise the response of different cell types from human skin. (2) We will exploit our extensive resource of cells obtained from DNA repair defective donors. (3) We will utilise new and existing monoclonal antibodies to DNA damage to resolve the significance of specific lesions in studies of the lethality, mutagenicity and clastogenicity of UVB. (4) We will resolve the contribution of UVB to immunomodulation by a study of adhesion molecules and extend our study to altered gene expression. (5) We will provide methods to assess individual exposure.
The programme of research is thus designed to provide a balance sheet of UVB damage, its repair, and its effects on gene expression in human skin. From this balance sheet it may be possible to resolve the contribution of UVB to skin cancer and immunosuppression. The information will help to provide a scientific justification for well-focussed protective or prophylatic measures and help to identify individuals at risk.
KEYWORDS UVB; Human cells; DNA repair deficiency; photoimmunology; clastogenicity; mutagenicity; DNA damage; oxidative damage; monoclonal antibodies; dosimeters
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine oncology skin cancer
- natural sciences biological sciences genetics DNA
- natural sciences earth and related environmental sciences environmental sciences ozone depletion
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Coordinator
BN1 9RR Brighton
United Kingdom
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