The Effect of Sun-Related Harmful Ultraviolet Rays

One of the main bases for skin cancer development is unprotected exposure to ultraviolet radiation. Chronic sunlight exposure leads the way for non-melanoma skin cancer prognosis1,2. Ultraviolet B (UVB) is the primary active waveband region that accounts for direct photochemical damage to DNA, by mutating the genes. Contrary to UVB, ultraviolet A (UVA) is responsible for the generation of reactive oxygen species, which have indirectly effects on DNA. The most lethal of skin cancers is frequently associated with occasional burning exposure to sunlight3,4. Ultraviolet radiation also causes various types of skin-related diseases, like skin aging and photodermatoses which is a skin rash caused by exposure to the sun.  However, responses in human skin vary according to wavelength5.

UVA-induced free radicals have long been studied as a contributor to photoaging and disease processes. Endogenous creation of radicals from cellular metabolism and exogenous related ultraviolet radiation and pollution can damage the skin on the cellular and tissue level. Free radicals basically are species that can exist freely with one or more unpaired electrons. In living organisms, free radicals are found in the state of reactive oxygen species (ROS), taking the form as oxygen-centered oxidizing agents. By its nature, ROS are volatile and unstable. In organisms, ROS add electrons (oxidize) to nearby molecules which disrupts their structure6.

Figure 1: Cellular and clinical effects of reactive oxygen species (ROS)1.

Exogenous ROS comes from environmental sources such as UVR, pollutants, and xenobiotics. UVA interacts with photosensitizers or chromophores in the skin. These chromophores absorb the energy from UVA wavelength and form an excited, unstable state. Transition to a stable state gives rise to released energy to nearby oxygen molecules to generate O2 and other ROS. Conjointly, these ROS can cause nonspecific cellular damage to DNA, protein, and lipid structures7,8. Prolonged exposure to UV radiation and pollutants produces a pro-oxidant state. The genetic integrity of a living organism can be disrupted by the resulting oxidative stress. Whereas UVB directly damages DNA, UVA takes steps by ROS intermediates. ROS-induced DNA damage can cause the formation of a modified guanine nucleotide (8-hydroxyguanine), single-stranded breaks, and oxidized pyrimidine bases. Mainly these damages are UVA related but have been observed in UVB-irradiated cells. The creation of 8-hydroxyguanine into DNA strands has been seen as a tumor promotion agent, suggesting that permanent DNA damage cause to mutagenesis and carcinogenesis9,10.

Harman first described the free radical theory of aging in 1956, announcing that free radical accumulation was contributing to the aging process. Undeniably, free radical damage on the skin by chronic ROS and UV stress plays a major role in photoaging. After UV exposure, ROS triggers a set of pathways to release some of the factors. Specifically, factors that regulate proteinases. Concerted, these proteases degrade the collagen and elastin fibers of the extracellular matrix. In addition, UVR-induced ROS have been shown to decrease transforming factor-β expression, which reduces collagen production and enhances elastin production. Consequently, ROS degrades the structural integrity of the skin by the way of altering the collagen and elastin units of the extracellular matrix. Thus, it creates weakened structural support8,11–14.

Figure 2: Extensive nuchal elastosis as a consequence of decades of sun exposure2.

It is known that induced immunosuppression of the skin can occur by UVA and UVB. The mechanism of UVA immunosuppression is not well known but a ROS-dependent mechanism has been involved. UVA-induced ROS can lead to lipid peroxidation, disturb redox potential, initiate AP-1 and NF-kB transcription, and eventually activate downstream cytokines (interleukin-4 and -10), which are responsible for systemic immunosuppression16,17.

Although the connection between UVR and photoaging is conveniently described, the mechanistic relation between ROS and skin cancer is still foggy. At the molecular level, ROS interferes with normal cell silencing by involving the expression of signal transduction genes. Abnormal AP-1 and NF-kB pathways have been implicated in cell proliferation and apoptosis leading to carcinogenesis. Halliday examined DNA from human actinic keratoses and squamous cell cancer for novel ROS mutations. A substantial number of mutations in both groups were found to be ROS stimulated on the p53 gene, indicating that ROS can be a mutagen, driving precursor lesion to malignancy17,18.

Figure 3: Inadequate sun protection resulting in sunburn as a consequence of sleeping in the sun2.

Conclusion

In summary, ultraviolet radiation can cause a serious extent of damage to living organisms. These damages usually occur gradually, thus harmful effects of UV rays are negligible by individuals. To reduce damaging effects following behavioral measures: wearing sun protective clothes to reduce sun exposure to minimum, complete avoidance of sun exposure, remaining under shade at times when wavelengths are intense, and proper application of a highly protective sunscreen over the exposed skin, is very effective to prevent or reduce ultraviolet-induced cellular damage to a minimum7,10.

References:

  1. van Kranen, H. J. et al. Dose-dependent effects of UVB-induced skin carcinogenesis in hairless p53 knockout mice. Mutat. Res. Mol. Mech. Mutagen. 571, 81–90 (2005).
  2. Dumaz, N. The role of UV-B light in skin carcinogenesis through the analysis of p53 mutations in squamous cell carcinomas of hairless mice. Carcinogenesis 18, 897–904 (1997).
  3. Curtin, J. A., Patel, H. N., Cho, K.-H. & LeBoit, P. E. Distinct Sets of Genetic Alterations in Melanoma. N. Engl. J. Med. 13 (2005).
  4. Landi, M. T. et al. MC1R Germline Variants Confer Risk for BRAF -Mutant Melanoma. Science 313, 521–522 (2006).
  5. Wulf, H. C., Sandby-Møller, J., Kobayasi, T. & Gniadecki, R. Skin aging and natural photoprotection. Micron 35, 185–191 (2004).
  6. Chen, L., Hu, J. Y. & Wang, S. Q. The role of antioxidants in photoprotection: A critical review. J. Am. Acad. Dermatol. 67, 1013–1024 (2012).
  7. Heck, D. E., Vetrano, A. M., Mariano, T. M. & Laskin, J. D. UVB Light Stimulates Production of Reactive Oxygen Species. J. Biol. Chem. 278, 22432–22436 (2003).
  8. Fisher, G. J. et al. Mechanisms of Photoaging and Chronological Skin Aging. Arch. Dermatol. 138, (2002).
  9. Valko, M., Rhodes, C. J., Moncol, J., Izakovic, M. & Mazur, M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem. Biol. Interact. 160, 1–40 (2006).
  10. Cadet, J. & Douki, T. Oxidatively Generated Damage to DNA by UVA Radiation in Cells and Human Skin. J. Invest. Dermatol. 131, 1005–1007 (2011).
  11. Harman, D. AGING: A THEORY BASED ON FREE RADICAL AND RADIATION CHEMISTRY. 3.
  12. Koch, H., Wittern, K.-P. & Bergemann, J. In Human Keratinocytes the Common Deletion Reflects Donor Variabilities Rather Than Chronologic Aging and can be Induced by Ultraviolet A Irradiation. J. Invest. Dermatol. 117, 892–897 (2001).
  13. Sárdy, M. Role of Matrix Metalloproteinases in Skin Ageing. Connect. Tissue Res. 50, 132–138 (2009).
  14. Bernstein, E. F. Reactive Oxygen Species Activate the Human Elastin Promoter in a Transgenic Model of Cutaneous Photoaging. Dermatol. Surg. 28, 132–135 (2002).
  15. Lautenschlager, S., Wulf, H. C. & Pittelkow, M. R. Photoprotection. The Lancet 370, 528–537 (2007).
  16. Ullrich, S. E. Mechanisms underlying UV-induced immune suppression. Mutat. Res. Mol. Mech. Mutagen. 571, 185–205 (2005).
  17. Halliday, G. M. Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis. Mutat. Res. Mol. Mech. Mutagen. 571, 107–120 (2005).
  18. Halliday, G. M., Russo, P. A. J., Yuen, K. S. & Robertson, B. O. Effect of inhibitors of oxygen radical and nitric oxide formation on UV radiation-induced erythema, immunosuppression and carcinogenesis. Redox Rep. 4, 316–319 (1999).

Figure References:

  1. Chen, L., Hu, J. Y. & Wang, S. Q. The role of antioxidants in photoprotection: A critical review. Am. Acad. Dermatol. 67, 1013–1024 (2012).
  2. Lautenschlager, S., Wulf, H. C. & Pittelkow, M. R. Photoprotection. The Lancet 370, 528–537 (2007).

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