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New bio-markers of oxidative stress to humans : a role in developing new strategies for human protection agains environmental (uva) damage to skin.

Cel

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.

Zaproszenie do składania wniosków

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System finansowania

CSC - Cost-sharing contracts

Koordynator

UNIVERSITY OF BATH
Wkład UE
Brak danych
Adres
Claverton Down
BA2 7AY BATH
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