Ultraviolet Radiation-Induced Immunomodulation: Skin Ageing and Cancer

  • Garima Suman
  • Shankar Suman


The prolonged exposure to ultraviolet radiation causes serious health issues to human beings. Skin is the largest and most visible organ of our body and most exposed to UV radiation. UV radiation is one of the most important environmental stressors responsible for causing skin damage. In this chapter, we have given an overview of the chronic effects of ultraviolet irradiation such as photoageing and cancer. The mechanisms underlying these effects include free radical-induced cell injury, direct and indirect DNA damage, genetic mutations, etc. We have elaborated on the risk factors and causes of UV-induced skin ageing and cancer in details. We have also enlisted the preventive measures that can minimize the UV-mediated chronic pathologies including premature ageing and cancer.


UV-R Photoageing Skin cancer DNA damage 


  1. Amaro-Ortiz, A., Yan, B., & D’Orazio, J. A. (2014). Ultraviolet radiation, ageing and the skin: Prevention of damage by topical cAMP manipulation. Molecules (Basel, Switzerland), 19, 6202–6219.PubMedCentralCrossRefGoogle Scholar
  2. Biniek, K., Levi, K., & Dauskardt, R. H. (2012). Solar UV radiation reduces the barrier function of human skin. Proceedings of the National Academy of Sciences, 109, 17111.CrossRefGoogle Scholar
  3. Chang, Y.-m., Barrett, J. H., Bishop, D. T., Armstrong, B. K., Bataille, V., Bergman, W., et al. (2009). Sun exposure and melanoma risk at different latitudes: A pooled analysis of 5700 cases and 7216 controls. International Journal of Epidemiology, 38, 814–830.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Cicarma, E., Juzeniene, A., Porojnicu, A. C., Bruland, Ø. S., & Moan, J. (2010). Latitude gradient for melanoma incidence by anatomic site and gender in Norway 1966–2007. Journal of Photochemistry and Photobiology B: Biology, 101, 174–178.CrossRefGoogle Scholar
  5. Cleaver, J. E., & Crowley, E. (2002). UV damage, DNA repair and skin carcinogenesis. Frontiers in Bioscience, 7, d1024–d1043.PubMedGoogle Scholar
  6. Coelho, S. G., Choi, W., Brenner, M., Miyamura, Y., Yamaguchi, Y., Wolber, R., et al. (2009). Short- and long-term effects of UV radiation on the pigmentation of human skin. The Journal of Investigative Dermatology Symposium Proceedings, 14, 32–35.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Flament, F., Bazin, R., Laquieze, S., Rubert, V., Simonpietri, E., & Piot, B. (2013). Effect of the sun on visible clinical signs of ageing in Caucasian skin. Clinical, Cosmetic and Investigational Dermatology, 6, 221–232.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Gilchrest, B. A., & Eller, M. S. (1999). DNA photodamage stimulates melanogenesis and other photoprotective responses. The Journal of Investigative Dermatology Symposium Proceedings, 4, 35–40.PubMedCrossRefPubMedCentralGoogle Scholar
  9. Gonzalez Maglio, D. H., Paz, M. L., & Leoni, J. (2016). Sunlight effects on immune system: Is there something Else in addition to UV-induced immunosuppression? BioMed Research International, 2016, 1934518.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Grant, W. B. (2008). The effect of solar UVB doses and vitamin D production, skin cancer action spectra, and smoking in explaining links between skin cancers and solid tumours. European Journal of Cancer, 44, 12–15.PubMedCrossRefPubMedCentralGoogle Scholar
  11. Griffiths, C., Russman, A. N., Majmudar, G., Singer, R. S., Hamilton, T. A., & Voorhees, J. J. (1993). Restoration of collagen formation in photodamaged human skin by Tretinoin (retinoic acid). New England Journal of Medicine, 329, 530–535.PubMedCrossRefPubMedCentralGoogle Scholar
  12. Haluza, D., Simic, S., & Moshammer, H. (2014). Temporal and spatial melanoma trends in Austria: An ecological study. International Journal of Environmental Research and Public Health, 11, 734–748.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Hammar, N., Linnersjo, A., Alfredsson, L., Dammstrom, B. G., Johansson, M., & Eliasch, H. (2002). Cancer incidence in airline and military pilots in Sweden 1961-1996. Aviation, Space, and Environmental Medicine, 73, 2–7.PubMedPubMedCentralGoogle Scholar
  14. Henri, P., Beaumel, S., Guezennec, A., Poumes, C., Stoebner, P. E., Stasia, M. J., et al. (2012). MC1R expression in HaCaT keratinocytes inhibits UVA-induced ROS production via NADPH oxidase- and cAMP-dependent mechanisms. Journal of Cellular Physiology, 227, 2578–2585.PubMedCrossRefPubMedCentralGoogle Scholar
  15. Hu, S., Ma, F., Collado-Mesa, F., & Kirsner, R. S. (2004). UV radiation, latitude, and melanoma in US Hispanics and blacks. Archives of Dermatology, 140, 819–824.PubMedCrossRefPubMedCentralGoogle Scholar
  16. Kadekaro, A. L., Chen, J., Yang, J., Chen, S., Jameson, J., Swope, V. B., et al. (2012). Alpha-melanocyte-stimulating hormone suppresses oxidative stress through a p53-mediated signalling pathway in human melanocytes. Molecular Cancer Research, 10, 778–786.PubMedCrossRefPubMedCentralGoogle Scholar
  17. Kim, Y. H., Yang, H. E., Park, B. K., Heo, M. Y., Jo, B. K., & Kim, H. P. (2002). The extract of the flowers of Prunus persica, a new cosmetic ingredient, protects against solar ultraviolet-induced skin damage in vivo. Journal of Cosmetic Science, 53, 27–34.PubMedPubMedCentralGoogle Scholar
  18. Krutmann, J., Morita, A., & Chung, J. H. (2012). Sun exposure: What molecular photodermatology tells us about its good and bad sides. Journal of Investigative Dermatology, 132, 976–984.PubMedCrossRefPubMedCentralGoogle Scholar
  19. Langton, A. K., Sherratt, M. J., Griffiths, C. E. M., & Watson, R. E. B. (2010). Review article: A new wrinkle on old skin: The role of elastic fibres in skin ageing. International Journal of Cosmetic Science, 32, 330–339.PubMedCrossRefPubMedCentralGoogle Scholar
  20. Lichte, V., Dennenmoser, B., Dietz, K., Häfner, H. M., Schlagenhauff, B., Garbe, C., et al. (2010). Professional risk for skin cancer development in male mountain guides – A cross-sectional study. Journal of the European Academy of Dermatology and Venereology, 24, 797–804.PubMedCrossRefPubMedCentralGoogle Scholar
  21. Liu, L., Xie, H., Chen, X., Shi, W., Xiao, X., Lei, D., et al. (2012). Differential response of normal human epidermal keratinocytes and HaCaT cells to hydrogen peroxide-induced oxidative stress. Clinical and Experimental Dermatology, 37, 772–780.PubMedCrossRefPubMedCentralGoogle Scholar
  22. Makrantonaki, E., & Zouboulis, C. C. (2007). Characteristics and Pathomechanisms of endogenously aged skin. Dermatology, 214, 352–360.PubMedCrossRefPubMedCentralGoogle Scholar
  23. McArdle, F., Rhodes, L. E., Parslew, R., Jack, C. I. A., Friedmann, P. S., & Jackson, M. J. (2002). UVR-induced oxidative stress in human skin in vivo: Effects of oral vitamin C supplementation. Free Radical Biology and Medicine, 33, 1355–1362.PubMedCrossRefPubMedCentralGoogle Scholar
  24. McAuliffe, D. J., & Blank, I. H. (1991). Effects of UVA (320-400 nm) on the barrier characteristics of the skin. The Journal of Investigative Dermatology, 96, 758–762.PubMedCrossRefPubMedCentralGoogle Scholar
  25. Meyskens, F. L., Jr., Farmer, P., & Fruehauf, J. P. (2001). Redox regulation in human melanocytes and melanoma. Pigment Cell Research, 14, 148–154.PubMedCrossRefPubMedCentralGoogle Scholar
  26. Mukherjee, S., Date, A., Patravale, V., Korting, H. C., Roeder, A., & Weindl, G. (2006). Retinoids in the treatment of skin ageing: An overview of clinical efficacy and safety. Clinical Interventions in Aging, 1, 327–348.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Muthusamy, V., & Piva, T. J. (2013). A comparative study of UV-induced cell signalling pathways in human keratinocyte-derived cell lines. Archives of Dermatological Research, 305, 817–833.PubMedCrossRefPubMedCentralGoogle Scholar
  28. Narayanan, D. L., Saladi, R. N., & Fox, J. L. (2010). Review: Ultraviolet radiation and skin cancer. International Journal of Dermatology, 49, 978–986.PubMedCrossRefPubMedCentralGoogle Scholar
  29. Naylor, E. C., Watson, R. E. B., & Sherratt, M. J. (2011). Molecular aspects of skin ageing. Maturitas, 69, 249–256.PubMedCrossRefPubMedCentralGoogle Scholar
  30. Packer, J. E., Slater, T. F., & Willson, R. L. (1979). Direct observation of a free radical interaction between vitamin E and vitamin C. Nature, 278, 737.PubMedCrossRefPubMedCentralGoogle Scholar
  31. Panich, U., Sittithumcharee, G., Rathviboon, N., & Jirawatnotai, S. (2016). Ultraviolet radiation-induced skin aging: The role of DNA damage and oxidative stress in epidermal stem cell damage mediated skin aging. Stem Cells International, 2016, 14.CrossRefGoogle Scholar
  32. Poljsak, B., & Dahmane, R. (2012). Free radicals and extrinsic skin aging. Dermatology Research and Practice, 2012, 135206.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Prunier, C., Masson-Genteuil, G., Ugolin, N., Sarrazy, F., & Sauvaigo, S. (2012). Aging and photo-ageing DNA repair phenotype of skin cells – Evidence toward an effect of chronic sun exposure. Mutation Research, 736, 48–55.PubMedCrossRefPubMedCentralGoogle Scholar
  34. Sakura, M., Chiba, Y., Kamiya, E., Furukawa, A., Kawamura, N., Niwa, M., et al. (2013). Spontaneous occurrence of photo ageing-like phenotypes in the dorsal skin of old SAMP1 mice, an oxidative stress model. Experimental Dermatology, 22, 62–64.PubMedCrossRefPubMedCentralGoogle Scholar
  35. Sander, C. S., Chang, H., Salzmann, S., Müller, C. S. L., Ekanayake-Mudiyanselage, S., Elsner, P., et al. (2002). Photoaging is associated with protein oxidation in human skin in vivo. Journal of Investigative Dermatology, 118, 618–625.PubMedCrossRefPubMedCentralGoogle Scholar
  36. Sarasin, A. (1999). The molecular pathways of ultraviolet-induced carcinogenesis. Mutation Research, 428, 5–10.PubMedCrossRefGoogle Scholar
  37. Schulz, I., Mahler, H. C., Boiteux, S., & Epe, B. (2000). Oxidative DNA base damage induced by singlet oxygen and photosensitization: Recognition by repair endonucleases and mutagenicity. Mutation Research, 461, 145–156.PubMedCrossRefPubMedCentralGoogle Scholar
  38. Serri, R., & Iorizzo, M. (2008). Cosmeceuticals: Focus on topical retinoids in photoaging. Clinics in Dermatology, 26, 633–635.PubMedCrossRefGoogle Scholar
  39. Shindo, Y., Witt, E., & Packer, L. (1993). Antioxidant defense mechanisms in murine epidermis and dermis and their responses to ultraviolet light. Journal of Investigative Dermatology, 100, 260–265.PubMedCrossRefPubMedCentralGoogle Scholar
  40. Song, X., Mosby, N., Yang, J., Xu, A., Abdel-Malek, Z., & Kadekaro, A. L. (2009). Alpha-MSH activates immediate defence responses to UV-induced oxidative stress in human melanocytes. Pigment Cell & Melanoma Research, 22, 809–818.CrossRefGoogle Scholar
  41. Stahl, W., Heinrich, U., Aust, O., Tronnier, H., & Sies, H. (2006). Lycopene-rich products and dietary photoprotection. Photochemical & Photobiological Sciences, 5, 238–242.CrossRefGoogle Scholar
  42. Stohs Sidney, J. (1995). The role of free radicals in toxicity and disease. Journal of Basic and Clinical Physiology and Pharmacology, 6(3–4), 205–228.Google Scholar
  43. Suzuki, I., Cone, R. D., Im, S., Nordlund, J., & Abdel-Malek, Z. A. (1996). Binding of melanotropic hormones to the melanocortin receptor MC1R on human melanocytes stimulates proliferation and melanogenesis. Endocrinology, 137, 1627–1633.PubMedCrossRefGoogle Scholar
  44. Velarde, M. C., Flynn, J. M., Day, N. U., Melov, S., & Campisi, J. (2012). Mitochondrial oxidative stress caused by Sod2 deficiency promotes cellular senescence and ageing phenotypes in the skin. Ageing, 4, 3–12.Google Scholar
  45. Vermeer, M., Schmieder, G. J., Yoshikawa, T., van den Berg, J. W., Metzman, M. S., Taylor, J. R., & Streilein, J. W. (1991). Effects of ultraviolet B light on cutaneous immune responses of humans with deeply pigmented skin. Journal of Investigative Dermatology, 97, 729–734.Google Scholar
  46. Volkmer, B., & Greinert, R. (2011). UV and children’s skin. Progress in Biophysics and Molecular Biology, 107, 386–388.PubMedCrossRefPubMedCentralGoogle Scholar
  47. Weerakkody, P., Jobling, J., Infante, M. M. V., & Rogers, G. (2010). The effect of maturity, sunburn and the application of sunscreens on the internal and external qualities of pomegranate fruit grown in Australia. Scientia Horticulturae, 124, 57–61.CrossRefGoogle Scholar
  48. Wei, Q., Lee, J. E., Gershenwald, J. E., Ross, M. I., Mansfield, P. F., Strom, S. S., et al. (2003). Repair of UV light-induced DNA damage and risk of cutaneous malignant melanoma. Journal of the National Cancer Institute, 95, 308–315.PubMedCrossRefGoogle Scholar
  49. Weiss, J. S., Ellis, C. N., Headington, J. T., & Voorhees, J. J. (1988). Topical tretinoin in the treatment of ageing skin. Journal of the American Academy of Dermatology, 19, 169–175.PubMedCrossRefPubMedCentralGoogle Scholar
  50. Wendt, J., Schanab, O., Binder, M., Pehamberger, H., & Okamoto, I. (2012). Site-dependent actinic skin damage as risk factor for melanoma in a central European population. Pigment Cell & Melanoma Research, 25, 234–242.CrossRefGoogle Scholar
  51. Yamamoto, O., Bhawan, J., Solares, G., Tsay, A. W., & Gilchrest, B. A. (1995). Ultrastructural effects of topical tretinoin on dermo-epidermal junction and papillary dermis in photodamaged skin. A controlled study. Experimental Dermatology, 4, 146–154.PubMedCrossRefPubMedCentralGoogle Scholar
  52. Yokoo, S., Furumoto, K., Hiyama, E., & Miwa, N. (2004). Slow-down of age-dependent telomere shortening is executed in human skin keratinocytes by hormesis-like-effects of trace hydrogen peroxide or by anti-oxidative effects of pro-vitamin C in common concurrently with reduction of intracellular oxidative stress. Journal of Cellular Biochemistry, 93, 588–597.PubMedCrossRefPubMedCentralGoogle Scholar
  53. Young, C. (2009). Solar ultraviolet radiation and skin cancer. Occupational Medicine (London), 59, 82–88.CrossRefGoogle Scholar
  54. Yun, J. S., Pahk, J. W., Lee, J. S., Shin, W. C., Lee, S. Y., & Hong, E. K. (2011). Inonotus obliquus protects against oxidative stress-induced apoptosis and premature senescence. Molecules and Cells, 31, 423–429.PubMedPubMedCentralCrossRefGoogle Scholar
  55. Zandi, S., Kalia, S., & Lui, H. (2012). UVA1 phototherapy: A concise and practical review. Skin Therapy Letter, 17, 1–4.PubMedPubMedCentralGoogle Scholar
  56. Zastrow, L., Groth, N., Klein, F., Kockott, D., Lademann, J., Renneberg, R., et al. (2009). The missing link – Light-induced (280–1,600 nm) free radical formation in human skin. Skin Pharmacology and Physiology, 22, 31–44.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Garima Suman
    • 1
  • Shankar Suman
    • 2
  1. 1.Department of Radio-DiagnosisTata Memorial HospitalMumbaiIndia
  2. 2.Department of Microbiology & Immunology, School of MedicineMeharry Medical College, School of MedicineNashvilleUSA

Personalised recommendations