Free radical formation in murine skin treated with tumour promoting organic peroxides.
The generation of free radicals from tumour-promoting organic peroxides applied to intact murine skin samples has been studied by EPR spectroscopy using two techniques: first direct observation of ascorbyl radicals produced from reactions of peroxide-related radicals with ascorbate, an important endogenous antioxidant, and secondly, observation of radical adducts produced by spin-trapping. Free radical generation from tumour-promoting organic peroxides can be seen to occur in intact skin tissue through a one-electron reductive pathway, and takes place at sites including the viable cells of the epidermis and/or dermis. This radical generation is dependent upon the penetration of the skin by the peroxides, with the stratum corneum representing a major diffusional barrier to their penetration of skin. The technique of using ascorbyl radical measurement by EPR spectroscopy as a means of studying and quantifying radical production in intact tissues, developed in this work, may prove of much use in the study of many free radicals and their reactions in a wide range of biological systems, particularly skin. When combined with appropriate spin-trapping techniques, which enable identification of radical species and elucidation of their mechanisms of production, this enables the direct, real-time observation of radical reactions and mechanisms not previously possible in intact tissue samples.
Department of Chemistry, University of York, UK.
G S
GS
Timmins
M J
MJ
Davies
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D003497:Cyclic N-Oxides; D003683:Dehydroascorbic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000378:metabolism / Q000633:toxicity; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010545:Peroxides / Q000378:metabolism* / Q000633:toxicity*; D012867:Skin / Q000187:drug effects*; D012878:Skin Neoplasms / Q000139:chemically induced*; D013113:Spin Labels
D003497:Cyclic N-Oxides; D005609:Free Radicals; D010545:Peroxides; D013113:Spin Labels; C000820:semidehydroascorbic acid; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid