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Free Radicals and Dermal Damage in Photoaging and Photocarcinogenesis

  • Chapter
Fundamentals for the Assessment of Risks from Environmental Radiation

Part of the book series: NATO Science Series ((ASEN2,volume 55))

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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 photo dermatological 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 in a better understanding of 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 scavengers, enhancers, and inhibitors for the activity of ROS detoxifying enzymes, using stably transfected fibroblast cell lines overexpressing ROS detoxifying enzymes, and using iron chelators blocking the Fenton reaction, distinct ROS have been increased peri-or intracellularly. A time and dose dependent increase in mRNA and protein levels for collagenase was observed after exposure of fibroblasts to UV-B, UV-A, O2, H2O2, O2 -,or OH generating systems. After UV-B irradiation inhibition of the Fenton reaction using iron chelators abrogated the MMP induction substantially. Scavengers for the hydroxyl radical reduced the MMP induction after UV-B, thus pointing to the importance of the Fenton reaction and the hydroxyl radical in the UV-B response. By modulating the lifetime of O2 by enhancers and quenchers, singlet oxygen could be identified as a crucial mediator of the UV-A response. In addition, the inhibition of glutathion peroxidase, catalase and the Fenton reaction enhanced MMP mRNA induction whereas inhibition of superoxide dismutase diminished the MMP mRNA increase. Furthermore, exposure to UV-A 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 UV-A irradiation, beside O2, 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 follow-ing UV irradiation. This will allow a rational risk assessment for the dermal damage of different UV modalities in photoaging and photocarcinogenesis.

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References

  1. Gilchrest, B.A. (1995) Photodamage. Blackwell Science, Cambridge MA

    Google Scholar 

  2. Kligman, L.H. (1992) UV-A induced biochemical changes in hairless mouse skin collagen: A contrast to UV-B effects. In: Urbach, F. (ed.) Biological Responses to Ultraviolet A Radiation. Valdemar Publishing, Overland Park, pp 209–216.

    Google Scholar 

  3. Oikarinen, A. (1990) The aging of skin: chronoaging versus photoaging. Photodermatol. Photoimmunol. Photomed. 7, 3–4.

    CAS  Google Scholar 

  4. Scharffetter-Kochanek, K., Wlaschek, M., Bolsen, K., Herrmann, G., Lehmann, P., Goerz, G., Mauch, C., and Plewig, G. (1992) Mechanisms of cutaneous photoaging. In: Plewig, G., Marks, R. (eds.). The environmental threat of the skin. Martin Dunitz Publishers, London, pp 72–82.

    Google Scholar 

  5. Brash, D.E. (1997) Sunlight and the onset of skin cancer. Trends Genetics 13 410–414.

    Article  CAS  Google Scholar 

  6. Scotto, J., and Fears, T.R (1987) The association of solar ultraviolet and skin melanoma incidence among caucasians in the United States. Cancer Invest. 5 275–283.

    CAS  Google Scholar 

  7. Gallagher, R.P., Hill, G.B., Bajdik, C.D, Fincham, S., Goldman, A.J., McLean, D.I., and Threlfall, W.J. (1995) Sunlight exposure, pigmentary factors, and risk of nonmelanocytic skin cancer. I. Basal cell carcinoma. Arch. Dermatol. 131 157–163.

    Article  CAS  Google Scholar 

  8. Gallagher, R.P., Hill, G.B., Bajdik, C.D., Fincham, S., Goldman, A.J., McLean, D.I., and Threlfall, W.J. (1995) Sunlight exposure, pigmentary factors, and risk of nonmelanocytic skin cancer. II. Squamous cell carcinoma. Arch. Dermatol. 131 164–169.

    Article  CAS  Google Scholar 

  9. Spencer, J.M., and Amonette, R.A. (1995) Indoor tanning: Risks, benefits and future trends. J. Am. Acad. Dermatol. 33 288–298.

    Article  CAS  Google Scholar 

  10. Coldiron, B.M. (1992) Thinning of the ozone layer: facts and consequences. J. Am. Acad. Dermatol. 27 783–785.

    Article  Google Scholar 

  11. Henriksen, T., Dahlback, A., Larsen, S.H.H., and Moan, J. (1990) Ultraviolet-radiation and skin cancer. Effect of an ozone layer depletion. Photochem. Photobiol. 51 579–582.

    Article  CAS  Google Scholar 

  12. Slaper, H., Velders, G.J.M., Daniel, J.S., de Gruijl, F.R., and van der Leun, J.C. (1996) Estimates of ozone depletion and skin cancer incidence to examine the Vienna Convention achievements. Nature 384 256–258.

    Article  CAS  Google Scholar 

  13. Black, H. (1987) Potential involvement of free radical reactions in ultraviolet light-mediated cutaneous damage. Photochem. Photobiol. 46 213–221.

    Article  CAS  Google Scholar 

  14. Cerutti, P.A. (1994) Oxy-radicals and cancer. Lancet 344 862–863.

    Article  CAS  Google Scholar 

  15. Scharffetter-Kochanek, K. (1997) Photodamage of the skin; prevention and therapie. In: Antioxidants in Disease - Mechanisms and Therapeutic Strategies. Sies, H. (ed), Series: Advances in Pharmacology. Academic Press, San Diego, pp 639–655.

    Google Scholar 

  16. Scharffetter-Kochanek, K., Wenk, J., Brenneisen, P., Blaudschun, R., and Wlaschek, M. (1997) Molecular Role of Reactive Oxygen Species in Photoaging and Tumor Progression. In: Altmeyer, P., Hoffmann, K., Stöcker, M. (eds.) Skin Cancer and UV Radiation. Springer Verlag, Berlin - Heidelberg New York, pp 115–127.

    Chapter  Google Scholar 

  17. Darr, D., and Fridovich, I. (1994) Free radicals in cutaneous biology. J. Invest. Dermatol. 102 671–675.

    Article  CAS  Google Scholar 

  18. Sies, H. (1991) Oxidative stress: oxidants and antioxidants. Academic Press, New York.

    Google Scholar 

  19. Remacle, J., Raes, M., Toussaint, O., Renard, P., and Rao, G. (1995) Low levels of reactive oxygen species as modulators of cell function. Mutat. Res. 316 103–122.

    Article  CAS  Google Scholar 

  20. Birkedal-Hansen, H., Moore, W.G, Bodden, M.K., Windsor, L.J., Birkedal-Hansen, B., De Carlo, A., and Engler, J.A. (1993) Matrix metalloproteinases: A Review. Crit. Rev. Oral Biol. Med. 4 197–250.

    CAS  Google Scholar 

  21. Stetler-Stevenson, W.G., Hewitt R., and Corcoran, M. (1996) Matrix metalloproteinases and tumor invasion: from correlation and causality to the clinic. Sem. Cancer BioL 7, 147–154.

    Article  CAS  Google Scholar 

  22. Boyd, D. (1996) Invasion and metastasis. CancerMetas. Res. 15 77–89.

    CAS  Google Scholar 

  23. Majmudar, G., Nelson, B.R., Jensen, T.C., Voorhees, J.J., and Johnson, T.M. (1994) Increased expression of stromelysin-3 in basal cell carcinomas. Mol. Carcinogen. 9 17–23.

    Article  CAS  Google Scholar 

  24. Woessner, J.F.Jr. (1991) Matrix metalloproteinases and their inhibitor in connective tissue remodeling. FASEB J. 5 2145–2154.

    CAS  Google Scholar 

  25. Rest, van der M., and Garrone, R. (1991) Collagen family of proteins. FASEB J. 5 2814–2823.

    Google Scholar 

  26. Brenneisen, P., Briviba, K., Wenk, J., Wlaschek, M., and Scharffetter-Kochanek, K. (1997) Hydrogen peroxide (H2O2) increases the steady-state mRNA levels of collagenase/MMP-1 in human dermal fibroblasts. Free Radic. Biol. Med. 22 515–524.

    Article  CAS  Google Scholar 

  27. Fisher, G.J., Talwary, H.S., Wang Z.Q., McPhillips, F., Kang, S., and Voorhees, J. (1996) UV-B activates stress - activated protein kinases, Fos/Jun driven dermis degrading proteinases in human skin in vivo. J. Invest. Dermatol., 107 449.

    Google Scholar 

  28. Herrmann, G., Wlaschek, M., Lange, T.S., Prenzel, K., Goerz, G., and Scharffetter-Kochanek, K. (1993) UV-A irradiation stimulates the synthesis of various matrix-metalloproteinases (MMPs) in cultured human fibroblasts. Exp. Dermatol. 2 92–97.

    Article  CAS  Google Scholar 

  29. Herrmann, G., Wlaschek, M., Bolsen, K., Prenzel, K., Goerz, G., and Scharffetter-Kochanek, K. (1996) Pathogenic implication of matrix-metalloproteinases (MMPs) and their counteracting inhibitor TIMP-1 in the cutaneous photodamage of human porphyria cutanea tarda (PCT). J. Invest. Dermatol. 107 398–403.

    Article  CAS  Google Scholar 

  30. Koivukangas, V., Kallioinen, M., Autio-Harmainen, H., and Oikarinen, A. (1994) UV irradiation induces the expression of gelatinases in human skin in vivo. Acta Derm. Venereol. 74 279–282.

    CAS  Google Scholar 

  31. Petersen, M.J., Hansen, C., and Craig, S. (1992) Ultraviolet A irradiation stimulates collagenase production in cultured human fibroblasts. J. Invest. Dermatol. 99 440–444.

    Article  CAS  Google Scholar 

  32. Scharffetter, K., Wlaschek, M., Hogg, A., Bolsen, K., Schothorst, A., Goerz, G., Krieg, T., and Plewig, G. (1991) UV-A irradiation induces collagenase in human dermal fibroblasts in vitro and in vivo. Arch. Dermatol. Res. 283 506–511.

    Article  CAS  Google Scholar 

  33. Stein, B., Rahmsdorf, H.J., Steffen, A., Litfin, M., and Herrlich, P. (1989) UV-induced DNA damage is an intermediate step in UV-induced expression of human immunodeficiency virus type I, collagenase, c-fos, and metallothionein. Mol. Cell. Biol. 9 5169–5181.

    CAS  Google Scholar 

  34. Nonakada, Y., Iwagaki, H., Kimura, T., Fuchimoto, S., and Orita, K. (1993) Effect of reactive oxygen intermediates on the in vitro invasive capacity of tumor cells and liver metastasis in mice. Int. J. Cancer 54 983–986.

    Article  Google Scholar 

  35. Taira, J., Mimura, K., Yoneya, T., Hagi, A., Murakami, A., and Makino, K. (1992) Hydroxyl radical formation by UV-irradiated epidermal cells. J. Biochem. 111 693–695.

    CAS  Google Scholar 

  36. Dalle-Carbonare, M., and Pathak, M.A. (1992) Skin photosensitizing agents and the role of reactive oxygen species in photoaging. J. Photochem. Photobiol. B 14 105–124.

    Article  CAS  Google Scholar 

  37. Jurkiewicz, B.A., Bissell, D.L., and Buettner, G.R. (1995) Effect of topically applied tocopherol on ultraviolet radiation-mediated free radical damage in skin. J. Invest. Dermatol. 104 484–488.

    Article  CAS  Google Scholar 

  38. Scharffetter-Kochanek, K., Wlaschek, M., Briviba, K., and Sies, H. (1993) Singlet oxygen induces collagenase expression in human skin fibroblasts. FEBS Lett. 331 304–306.

    Article  CAS  Google Scholar 

  39. Halliwell, B., and Aruoma, O.I. (1991) DNA damage by oxygen-derived species. Its mechanism and measurement in mammalian systems. FEBS Lett. 281 9–19.

    Article  CAS  Google Scholar 

  40. Wlaschek, M., Briviba, K., Stricklin, G.P., Sies, H., and Scharffetter-Kochanek, K. (1995) Singlet oxygen may mediate the ultraviolet A induced synthesis of interstitial collagenase. J. Invest. Dermatol. 104 194–198.

    Article  CAS  Google Scholar 

  41. Wlaschek, M., Wenk, J., Brenneisen, P., Briviba, K., Schwarz, A., Sies, H., and ScharffetterKochanek, K. (1997) Singlet oxygen is an early intermediate in cytokine-dependent ultraviolet-A induction of interstitial collagenase in human dermal fibroblasts in vitro. FEBS Lett. 413 239–242

    Article  CAS  Google Scholar 

  42. Wlaschek, M., Bolsen, K., Hermann, G., Schwarz, A., Wilmroth, F., Heinrich, P.C., Goerz, G., and Scharffetter-Kochanek, K. (1993) UV-A-induced autocrine stimulation of fibroblast-derivedcollagenase by IL-6: A possible mechanism in dermal photodamage? J. Invest. Dermatol. 101 164–168.

    Article  CAS  Google Scholar 

  43. Wlaschek, M., Heinen, G., Poswig, A., Schwarz, A., Krieg, T., and Scharffetter-Kochanek, K. (1994) UV-A-induced stimulation of fibroblast-derived collagenase/MMP-1 by interrelated loops of interleukin-1 and interleukin-6. Photochent Photobiol. 59 550–556.

    Article  CAS  Google Scholar 

  44. Kraemer, M., Sachsenmaier, C., Herrlich, P., and Rahmsdorf H.J. (1993) UV irradiation-induced interleukin-1 and basic fibroblast growth factor synthesis and release mediate part of the UV response. J. Biol. Chem. 268 6734–6741.

    CAS  Google Scholar 

  45. Minden, A., Lin, A., Smeal, T., Derijard, B., Cobb, M., Davis, R., and Karin, M. (1994) C-jun N-terminal phosphorylation correlates with activation of the JNK subgroup but not the ERK subgroup of mitogen-activated protein kinases. Mol. Cell Biol. 14 6683–6688.

    CAS  Google Scholar 

  46. Brenneisen, P., Wenk, J., Lkozu, O., Wlaschek, M., Briviba, K., Krieg, T., Sies, H., ScharffetterKochanek, K. (1998) Central role of ferrous/ferric iron in the ultraviolet B irradiation-mediated signaling pathway leading to increased interstitial collagenase (matrix-degrading metalloprotease (MMP-1) and stromelysin-1 (MMP-3)) m-RNA levels in cultured human dermal fibroblasts. J. Biol. Chem. 273 5279–5289

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Dermatology, University of Cologne, Joseph-Stelzmann Str. 9, D-50924, Cologne, Germany

    K. Scharffetter-Kochanek, P. Brenneisen, J. Wenk, R. Blaudschun, M. Schauen & M. Wlaschek

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  1. K. Scharffetter-Kochanek
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  2. P. Brenneisen
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  3. J. Wenk
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  4. R. Blaudschun
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  5. M. Schauen
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  6. M. Wlaschek
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Editors and Affiliations

  1. Radiation Biology Section, DLR Institute of Aerospace Medicine, Cologne, Germany

    Christa Baumstark-Khan  & Gerda Horneck  & 

  2. Czech Academy of Sciences, Institute of Biophysics, Brno, Czech Republic

    Stanislav Kozubek

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Scharffetter-Kochanek, K., Brenneisen, P., Wenk, J., Blaudschun, R., Schauen, M., Wlaschek, M. (1999). Free Radicals and Dermal Damage in Photoaging and Photocarcinogenesis. In: Baumstark-Khan, C., Kozubek, S., Horneck, G. (eds) Fundamentals for the Assessment of Risks from Environmental Radiation. NATO Science Series, vol 55. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-4585-5_45

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  • DOI: https://doi.org/10.1007/978-94-011-4585-5_45

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-0-7923-5668-4

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