Objective Research objectives and content 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 medical and health sciencesclinical medicineoncologyskin cancernatural sciencesbiological sciencesgeneticsDNAnatural sciencesearth and related environmental sciencesenvironmental sciencesozone depletionnatural sciencesearth and related environmental sciencesgeologypetrology Programme(s) FP4-TMR - Specific research and technological development programme in the field of the training and mobility of researchers, 1994-1998 Topic(s) 0301 - Post-graduate research training grants Call for proposal Data not available Funding Scheme Data not available Coordinator UNIVERSITY OF MANCHESTER EU contribution No data Address Oxford Road M13 9PL MANCHESTER United Kingdom See on map Total cost No data
