Objetivo
The objective of this proposal is to develop new bio-markers based on changes in gene expression and mitochondrial damage which may be used to monitor exposure and susceptibility to oxidative stress from the environment and to validate this methodology using the model of acute and chronic skin exposure to the environmental oxidising carcinogen, ultraviolet A radiation. The major dietary antioxidant phenolic compounds and their metabolites will then be examined for a potential protective role in the skin against environmental stress.
Scientific approach
Bio-markers of acute and chronic stress to humans will be developed which will be exploited to monitor changes due to the environmental stress of solar ultraviolet A radiation on the skin. The bio-markers will be designed to have wider applicability and initially will be tested in skin cells (fibroblasts and keratinocytes) and freshly isolated lymphocytes. An existing bio-marker of oxidative damage to cells and tissues (8 hydroxydG in DNA) will be exploited and new ones developed based on the extremely sensitive alterations in acute and chronic (adaptive) gene expression and mitochondrial DNA damage that occur in cells/tissues after oxidative stress.
In parallel with these studies, information will be obtained as to how the most important dietary phenolic compounds are metabolised in the intestine, the antioxidant properties of such metabolites and the nature of phenolics and their metabolites which eventually appear in the skin. Examination of how such compounds are modified by UV in vitro and when present in the skin will be undertaken. In vitro testing will be carried out using the newly developed bio-markers with a panel of cell types to determine which dietary antioxidants and their metabolites are most suitable for protection against UVA.
Another essential step is to test existing and newly developed bio-markers in human skin biopsies (to be distributed to all partners) taken from sun-protected areas and chronically sun-exposed areas. Based on all the preceding studies and by the end of the second year, clear decisions can be made on the most suitable panel of bio-markers to use in human intervention studies and the nature of phenolic antioxidant compounds to be employed. A suitable dietary supplementation regime will then be designed and carried out using selected volunteers who will be subjected to acute and repeated doses of UVA radiation from well characterised broad spectrum UVA sources.
Simultaneously, with the dietary supplementation study, a second study will be carried out using topical antioxidants. Skin biopsies will be taken at all stages of both human studies and distributed to the participating laboratories for bio-marker and antioxidant analysis. Bio-markers of acute and chronic stress to humans will be developed which will be exploited to monitor changes due to the environmental stress of solar ultraviolet A radiation on the skin. The bio-markers will be designed to have wider applicability and initially will be tested in skin cells (fibroblasts and keratinocytes) and freshly isolated lymphocytes. An existing bio-marker of oxidative damage to cells and tissues (8 hydroxydG in DNA) will be exploited and new ones developed based on the extremely sensitive alterations in acute and chronic (adaptive) gene expression and mitochondrial DNA damage that occur in cells/tissues after oxidative stress. In parallel with these studies, information will be obtained as to how the most important dietary phenolic compounds are metabolised in the intestine, the antioxidant properties of such metabolites and the nature of phenolics and their metabolites which eventually appear in the skin. Examination of how such compounds are modified by UV in vitro and when present in the skin will be undertaken.
In vitro testing will be carried out using the newly developed bio-markers with a panel of cell types to determine which dietary antioxidants and their metabolites are most suitable for protection against UVA. Another essential step is to test existing and newly developed bio-markers in human skin biopsies (to be distributed to all partners) taken from sun-protected areas and chronically sun-exposed areas. Based on all the preceding studies and by the end of the second year, clear decisions can be made on the most suitable panel of bio-markers to use in human intervention studies and the nature of phenolic antioxidant compounds to be employed. A suitable dietary supplementation regime will then be designed and carried out using selected volunteers who will be subjected to acute and repeated doses of UVA radiation from well characterised broad spectrum UVA sources.
Additionally, with the dietary supplementation study, a second study will be carried out using topical antioxidants. Skin biopsies will be taken at all stages of both human studies and distributed to the participating laboratories for bio-marker and antioxidant analysis.
Ámbito científico (EuroSciVoc)
CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural. Véas: El vocabulario científico europeo..
CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural. Véas: El vocabulario científico europeo..
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Las convocatorias de propuestas se dividen en temas. Un tema define una materia o área específica para la que los solicitantes pueden presentar propuestas. La descripción de un tema comprende su alcance específico y la repercusión prevista del proyecto financiado.
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Procedimiento para invitar a los solicitantes a presentar propuestas de proyectos con el objetivo de obtener financiación de la UE.
Régimen de financiación
Régimen de financiación (o «Tipo de acción») dentro de un programa con características comunes. Especifica: el alcance de lo que se financia; el porcentaje de reembolso; los criterios específicos de evaluación para optar a la financiación; y el uso de formas simplificadas de costes como los importes a tanto alzado.
Régimen de financiación (o «Tipo de acción») dentro de un programa con características comunes. Especifica: el alcance de lo que se financia; el porcentaje de reembolso; los criterios específicos de evaluación para optar a la financiación; y el uso de formas simplificadas de costes como los importes a tanto alzado.
Coordinador
BA2 7AY BATH
Reino Unido
Los costes totales en que ha incurrido esta organización para participar en el proyecto, incluidos los costes directos e indirectos. Este importe es un subconjunto del presupuesto total del proyecto.