Wavelength dependent generation of singlet oxygen in the UV region of 280 to 400 nm by endogenous photosensitizers in solutions and skin cells

• Applicant: Dr. Johannes Regensburger
• Subject Area: Dermatology
• Term: from 2013 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 234392985

In addition to the undeniably positive effects of sunlight, the contained ultraviolet radiation can cause sunburn, premature skin aging and skin cancer. The underlying damage mechanisms investigated and evaluated in vitro are generally separated in the respective spectral areas UVA (320-400 nm) and UVB (280-320 nm). The UVB radiation is absorbed directly by DNA and causes damage to the skin cells by the formation of cyclobutane pyrimidine dimers and pyrimidine pyrimidone photoproducts. UVA radiation (340-400 nm), however, is absorbed by other molecules (endogenous photosensitizers) in the cells, where the absorbed energy can be transferred to molecular oxygen. This highly reactive singlet oxygen is formed temporarily, which causes oxidative damage as well as regulatory effects in the skin cells.Preliminary results have shown that the separation in either pure radiation absorption (UVB) or oxidative damage (UVA) is so not to maintain. Also UVB radiation can produce singlet oxygen, and here among others vitamins and fatty acids are involved as endogenous photosensitizers. To what extent UVB radiation generates singlet oxygen in skin cells and what role this plays for the cellular damage mechanisms, is currently not known. In addition, it was shown that endogenous photosensitizers irradiated by UVA or UVB radiation change their ability to generate singlet oxygen the significantly.First, by using luminescence spectroscopy, it will be investigated, to what extent singlet oxygen can be created at shorter wavelengths (280-340 nm) by not yet examined endogenous photosensitizers. Also, it shall be clarified whether the known damage mechanisms in cells are affected. Second, it will be investigated to what extent UV radiation chemically modifies the endogenous photosensitizers during irradiation, as well as their efficaccy to generate singlet oxygen. Therefore, the photosensitizers should be irradiated with UVA or UVB individually, sequentially or in parallel. These steps are carried out according to the requirements in solution and on keratinocytes and fibroblasts in vitro. Third, the regulation of Matrix Metallo Proteinases, Interleukins and MAP kinases are correlated with the generation of singlet oxygen under the various irradiation conditions.After performing these steps, it should be clarified whether and to what extent the production of singlet oxygen in the entire UV spectrum contributes to the damage of cells. Further it should be clarified to what extent by parallel irradiation with UVA and UVB (such as sunlight) and the photochemical change of endogenous photosensitizers during irradiation, the role of singlet oxygen is to re-evaluate in the cellular damage patterns.

• DFG Programme: Research Grants