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Skin Cancer and UV Radiation pp 115–127Cite as

Molecular Role of Reactive Oxygen Species in Photoaging and Tumor Progression

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Abstract

The increase in UV irradiation on earth due to the stratospheric ozone depletion represents a major environmental threat to the skin increasing its risk of photooxidative damage by reactive oxygen species (ROS). ROS have been implicated in several photodermatological disorders including photoaging. The clinical manifestations of cutaneous photoaging are due to quantitative and qualitative alterations of the dermal connective tissue. Therefore, we were interested to better define the involvement of ROS in the up-regulation of matrix-metalloproteinases (MMP) responsible for connective tissue degradation in photoaging, tumor invasion and metastasis. For this purpose fibroblast monolayer cultures have been subjected to various UV modalities. In parallel fibroblasts have been challenged by distinct ROS generating systems. Using non-toxic concentrations of scavengers, enhancers, and chemicals which specifically inhibit the activities of ROS detoxifying enzymes, stably transfected fibroblast cell lines overexpressing ROS detoxifying enzymes, and iron chelators blocking the Fenton reaction, distinct ROS have been increased perior intracellularly. A time and dose dependent increase in mRNA and protein levels for collagenase was observed after exposure of fibroblasts to UVB, UVA, 1O2, H2O2, O2, or OH generating systems. After UVB irradiation inhibition of the Fenton reaction using iron chelators abrogated the MMP induction substantially. Scavengers for the hydroxyl radical reduced the MMP induction after UVB, thus pointing to the importance of the Fenton reaction and the hydroxyl radical in the UVB response. By modulating the lifetime of 1O2 by enhancers and quenchers, singlet oxygen could be identified as a crucial mediator of the UVA response. In addition, the inhibition of glutathione peroxidase, catalase and the Fenton reaction enhanced MMP mRNA induction whereas inhibition of superoxide dismutase diminished the MMP mRNA increase. Furthermore, exposure to UVA of a stably transfected fibroblast cell line overexpressing the manganese superoxide dismutase resulted in a substantial increase in MMP mRNA. These results indicate that following UVA irradiation, beside 1O2, H2O2 is mainly responsible for the induction of MMP synthesis. In conclusion, we have identified distinct ROS involved in matrix-degrading enzyme induction resulting in tissue degradation following UV irradiation and have outlined preventive strategies which may enhance the rational development of photoprotective agents.

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  1. K. Scharffetter-Kochanek
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  2. J. Wenk
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  3. P. Brenneisen
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  4. R. Blaudschun
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  5. M. Wlaschek
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  1. Dermatologische Klinik der Ruhr-Universität Bochum, im St. Josef Hospital, Gudrunstraße 56, D-44791, Bochum, Germany

    Peter Altmeyer , Klaus Hoffmann  & Markus Stücker ,  & 

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Scharffetter-Kochanek, K., Wenk, J., Brenneisen, P., Blaudschun, R., Wlaschek, M. (1997). Molecular Role of Reactive Oxygen Species in Photoaging and Tumor Progression. In: Altmeyer, P., Hoffmann, K., Stücker, M. (eds) Skin Cancer and UV Radiation. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60771-4_13

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