Cited by 292Skin Protection and AgingDNA Repair MechanismsNonmelanoma Skin Cancer Studies

Enzyme plus light therapy to repair DNA damage in ultraviolet-B-irradiated human skin

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Stege, Helger, Roza, Len, Vink, Arie A., Grewe, Markus, Ruzicka, Thomas, Grether-Beck, Susanne, Krutmann, Jean·2000·Proceedings of the National Academy of Sciences

Abstract

Ultraviolet-B (UVB) (290–320 nm) radiation-induced cyclobutane pyrimidine dimers within the DNA of epidermal cells are detrimental to human health by causing mutations and immunosuppressive effects that presumably contribute to photocarcinogenesis. Conventional photoprotection by sunscreens is exclusively prophylactic in nature and of no value once DNA damage has occurred. In this paper, we have therefore assessed whether it is possible to repair UVB radiation-induced DNA damage through topical application of the DNA-repair enzyme photolyase, derived from Anacystis nidulans , that specifically converts cyclobutane dimers into their original DNA structure after exposure to photoreactivating light. When a dose of UVB radiation sufficient to induce erythema was administered to the skin of healthy subjects, significant numbers of dimers were formed within epidermal cells. Topical application of photolyase-containing liposomes to UVB-irradiated skin and subsequent exposure to photoreactivating light decreased the number of UVB radiation-induced dimers by 40–45%. No reduction was observed if the liposomes were not filled with photolyase or if photoreactivating exposure preceded the application of filled liposomes. The UVB dose administered resulted in suppression of intercellular adhesion molecule-1 (ICAM-1), a molecule required for immunity and inflammatory events in the epidermis. In addition, in subjects hypersensitive to nickel sulfate, elicitation of the hypersensitivity reaction in irradiated skin areas was prevented. Photolyase-induced dimer repair completely prevented these UVB radiation-induced immunosuppressive effects as well as erythema and sunburn-cell formation. These studies demonstrate that topical application of photolyase is effective in dimer reversal and thereby leads to immunoprotection.

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  1. [21]Nickoloff, B. J. (1989) in The Skin Immune System , ed. Bos, J. D. (CRC, Boca Raton, FL), pp. 49-74.
  2. [23]Ahrens, C., Grewe, M., Berneburg, M., Grether-Beck, S., Quilliet, X., Mezzina, M., Sarasin, A., Lehmann, A. R., Arlett, C. F. & Krutmann, J. (1997) Proc. Natl. Acad. Sci. USA 94, 6837-6841.
  3. [24]Cooper, K. D., Oberhelman, L., Hamilton, T. A., Baadsgaard, O., Terhune, M., LeVee, G., Anderson, T. & Koren, H. (1992) Proc. Natl. Acad. Sci. USA 89, 8497-8501.
  4. [28]Ley, R. (1985) Proc. Natl. Aacd. Sci. USA 82, 2409-2411.
  5. [32]Kulms, D., Po ¨ppelmann, B., Yarosh, D., Luger, T. A., Krutmann, J. & Schwarz, T. (1999) Proc. Natl. Acad. Sci. USA 96, 7974-7979.

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Authors
Stege, H., Roza, L., Vink, A. A., Grewe, M., Ruzicka, T., Grether-Beck, S., & Krutmann, J.
Affiliations
  • Heinrich Heine University Düsseldorf (DE)
  • Clinical and Experimental Photodermatology, Department of Dermatology, Heinrich Heine University, D-40225 Düsseldorf, Germany; Skin Effects Testing and Photobiology, Netherlands Central Organization for Applied Scientific Research Nutrition and Food Research Institute, 3700 AJ Zeist, The Netherlands
Venue
Proceedings of the National Academy of Sciences
Published
2000-01-31
Volume
97
Issue
4
Pages
1790-1795
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2055660529
Cited by
292
References
34
Citations by year
2026: 5 · 2025: 9 · 2024: 6 · 2023: 5 · 2022: 11 · 2021: 8 · 2020: 4 · 2019: 17 · 2018: 5 · 2017: 6 · 2016: 15 · 2015: 7 · 2014: 6 · 2013: 10 · 2012: 3
FWCI
19.14
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Dermatology › Skin Protection and Aging
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Health Sciences › Medicine › Epidemiology › Nonmelanoma Skin Cancer Studies
Keywords
UV-B radiation, cyclobutane pyrimidine dimers, photolyase, Anacystis nidulans, photoreactivation, DNA repair, epidermal cells, immunosuppression, ICAM-1, nickel allergy, erythema, sunburn cells, photoprotection, photocarcinogenesis
MeSH terms
Adult, Cyanobacteria, Dermatitis, Contact, DNA Damage, Deoxyribodipyrimidine Photo-Lyase, DNA Repair, Fluorescent Antibody Technique, Humans, Immunosuppressive Agents, Interferon-gamma, Lymphocytes, Male, Microscopy, Fluorescence, Nickel, Proteolipids, Pyrimidine Dimers, Skin, Ultraviolet Rays, Keratinocytes, Intercellular Adhesion Molecule-1

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