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Cellular studies with UVA radiation: A role for iron


Reference:

Tyrrell, R. M., Pourzand, C. A., Brown, J., Hejmadi, V., Kvam, E., Ryter, S. and Watkin, R. D., 2000. Cellular studies with UVA radiation: A role for iron. Radiation Protection Dosimetry, 91 (1-3), pp. 37-39.

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Abstract

The UVA (320-380 nm) component-of sunlight or sunbeds acts as an oxidising carcinogen and has been clearly implicated in skin cancer. Since WA radiation interacts with cells by generating active oxygen species, the damaging effects of this radiation will be exacerbated by the presence of catalytically reactive iron in cells. It has now been shown by two independent techniques (dequenching of metal-quenched calcein fluorescence in cells and changes in the binding activity of the iron responsive protein IRP1) that WA radiation causes an immediate release of 'free' iron in human skin fibroblasts via the proteolysis of ferritin (Ft). Within minutes of exposure to a range of doses of WA at natural exposure levels, the binding activity of IRP-1, as well as Ft levels, decrease in a dose-dependent manner. It-is proposed that the oxidative damage to lysosomes that leads to Ft degradation and the consequent release of potentially harmful 'free' iron to the cytosol might be a major factor in WA-induced damage to the skin. UVA radiation also breaks down heme-containing proteins in the microsomal membrane to release free heme as an additional photosensitising component. This will provide another source of enhanced free iron in skin cells since constitutive heme oxygenase 2 (in keratinocytes) and UVA-inducible heme oxygenase-1 (in fibroblasts) are likely to break down any free heme to biliverdin and release iron and carbon monbxide in the process. It is postulated that, in skin fibroblasts, this free heme release and the enhanced free iron pools will lead to an adaptive response involving heme oxygenase (with a maximum about 10 h) and ferritin (in 24-48 h) that will scavenge the heme and iron released by subsequent oxidising (UVA) treatments.

Details

Item Type Articles
CreatorsTyrrell, R. M., Pourzand, C. A., Brown, J., Hejmadi, V., Kvam, E., Ryter, S. and Watkin, R. D.
DepartmentsFaculty of Science > Pharmacy & Pharmacology
RefereedYes
StatusPublished
ID Code19963
Additional InformationInternational Workshop on Ultraviolet Radiation Exposure, Measurement and Protection. 18-20 October, 1999. Oxford, England

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