Ultraviolet (UV) radiation in sunlight is cytotoxic and, in overdosages, clearly detrimental to the skin, as becomes manifest in common sunburn reactions in which epidermal cells die in apoptosis (“sunburn cells”) and strong inflammation occurs (vasodilation, extravasation, and infiltrates of leukocytes), turning the skin red (erythema) and swollen (edema). In excessive cases the skin ends up peeling, or it may even develop blisters. Fair-skinned people are clearly most susceptible to these sunburn reactions. Although these dramatic reactions may leave a different impression, it appears that the skin is quite well adapted to the persistent UV challenge in its natural environment – even the excessive reactions may be considered part of a formidable adaptation.
Access provided by Autonomous University of Puebla. Download to read the full chapter text
Chapter PDF
Similar content being viewed by others
Keywords
- Mycophenolate Mofetil
- Nucleotide Excision Repair
- Hairless Mouse
- Cyclobutane Pyrimidine Dimer
- Skin Carcinoma
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Reference
Kripke ML. Antigenicity of murine skin tumors induced by ultraviolet light. J Natl Cancer Inst 1974; 53:1333–6.
Kelly GE, Meikle W, Sheil AG. Scheduled and unscheduled DNA synthesis in epidermal cells of hairless mice treated with immunosuppressive drugs and UVB-UVA irradiation. Br J Dermatol 1987; 117:429–40.
de Gruijl FR. Skin cancer and solar UV radiation. Eur J Cancer 1999; 35:2003–9.
Kielbassa C, Roza L, Epe B. Wavelength dependence of oxidative DNA damage induced by UV and visible light. Carcinogenesis 1997; 18:811–6.
Mouret S, Baudouin C, Charveron M, Favier A, Cadet J, Douki T. Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin exposed to UVA radiation. Proc Natl Acad Sci U S A 2006; 103:13765–70.
Garinis GA, Mitchell JR, Moorhouse MJ, Hanada K, de Waard H, Vandeputte D, Jans J, Brand K, Smid M, van der Spek PJ, Hoeijmakers JH, Kanaar R, van der Horst GT. Transcriptome analysis reveals cyclobutane pyrimidine dimers as a major source of UV-induced DNA breaks. EMBO J 2005; 24:3952–62.
Kelly GE, Meikle WD, Moore DE. Enhancement of UV-induced skin carcinogenesis by azathioprine: role of photochemical sensitisation. Photochem Photobiol 1989; 49:59–65.
O’Donovan P, Perrett CM, Zhang X, Montaner B, Xu YZ, Harwood CA, McGregor JM, Walker SL, Hanaoka F, Karran P. Azathioprine and UVA light generate mutagenic oxidative DNA damage. Science 2005; 309:1871–4.
Berg RJ, Ruven HJ, Sands AT, de Gruijl FR, Mullenders LH. Defective global genome repair in XPC mice is associated with skin cancer susceptibility but not with sensitivity to UVB induced erythema and edema. J Invest Dermatol 1998; 110:405–9.
Yarosh DB, Pena AV, Nay SL, Canning MT, Brown DA. Calcineurin inhibitors decrease DNA repair and apoptosis in human keratinocytes following ultraviolet B irradiation. J Invest Dermatol 2005; 125:1020–5.
Kelly GE, Meikle W, Sheil AG. Effects of immunosuppressive therapy on the induction of skin tumors by ultraviolet irradiation in hairless mice. Transplantation 1987; 44:429–34.
Offman J, Opelz G, Doehler B, Cummins D, Halil O, Banner NR, Burke MM, Sullivan D, Macpherson P, Karran P. Defective DNA mismatch repair in acute myeloid leukemia/myelodysplastic syndrome after organ transplantation. Blood 2004; 104:822–8.
Han J, Colditz GA, Samson LD, Hunter DJ. Polymorphisms in DNA double-strand break repair genes and skin cancer risk. Cancer Res 2004; 64:3009–13.
Wang LE, Xiong P, Strom SS, Goldberg LH, Lee JE, Ross MI, Mansfield PF, Gershenwald JE, Prieto VG, Cormier JN, Duvic M, Clayman GL, Weber RS, Lippman SM, Amos CI, Spitz MR, Wei Q. In vitro sensitivity to ultraviolet B light and skin cancer risk: a case-control analysis. J Natl Cancer Inst 2005; 97:1822–31.
Huang S, Liu LN, Hosoi H, Dilling MB, Shikata T, Houghton PJ. p53/p21(CIP1) cooperate in enforcing rapamycin-induced G(1) arrest and determine the cellular response to rapamycin. Cancer Res 2001; 61:3373–81.
Brash DE, Haseltine WA. UV-induced mutation hotspots occur at DNA damage hotspots. Nature 1982; 298:189–92.
Brash DE, Ziegler A, Jonason AS, Simon JA, Kunala S, Leffell DJ. Sunlight and sunburn in human skin cancer: p53, apoptosis, and tumor promotion. J Invest Dermatol Symp Proc 1996; 1:136–42.
Rebel H, Kram N, Westerman A, Banus S, van Kranen HJ, de Gruijl FR. Relationship between UV-induced mutant p53 patches and skin tumours, analysed by mutation spectra and by induction kinetics in various DNA-repair-deficient mice. Carcinogenesis 2005; 26:2123–30.
Remenyik E, Wikonkal NM, Zhang W, Paliwal V, Brash DE. Antigen-specific immunity does not mediate acute regression of UVB-induced p53-mutant clones. Oncogene 2003; 22:6369–76.
McGregor JM, Berkhout RJ, Rozycka M, ter Schegget J, Bouwes Bavinck JN, Brooks L, Crook T. p53 mutations implicate sunlight in post-transplant skin cancer irrespective of human papillomavirus status. Oncogene 1997; 15:1737–40.
Queille S, Luron L, Spatz A, Avril MF, Ribrag V, Duvillard P, Hiesse C, Sarasin A, Armand JP, Daya-Grosjean L. Analysis of skin cancer risk factors in immunosuppressed renal transplant patients shows high levels of UV specific tandem CC to TT mutations of the p53 gene. Carcinogenesis 2007; 28(3):724–31.
Ashton KJ, Weinstein SR, Maguire DJ, Griffiths LR. Chromosomal aberrations in squamous cell carcinoma and solar keratoses revealed by comparative genomic hybridization. Arch Dermatol 2003; 139:876–82.
Pelisson I, Soler C, Chardonnet Y, Euvrard S, Schmitt D. A possible role for human papillomaviruses and c-myc, c-Ha-ras, and p53 gene alterations in malignant cutaneous lesions from renal transplant recipients. Cancer Detect Prev 1996; 20:20–30.
Hojo M, Morimoto T, Maluccio M, Asano T, Morimoto K, Lagman M, Shimbo T, Suthanthiran M. Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature 1999; 397:530–4.
Stracke S, Ramudo L, Keller F, Henne-Bruns D, Mayer JM. Antiproliferative and overadditive effects of everolimus and mycophenolate mofetil in pancreas and lung cancer cells in vitro. Transplant Proc 2006; 38:766–70.
Koehl GE, Andrassy J, Guba M, Richter S, Kroemer A, Scherer MN, Steinbauer M, Graeb C, Schlitt HJ, Jauch KW, Geissler EK. Rapamycin protects allografts from rejection while simultaneously attacking tumors in immunosuppressed mice. Transplantation 2004; 77:1319–26.
Mathew T, Kreis H, Friend P. Two-year incidence of malignancy in sirolimus-treated renal transplant recipients: results from five multicenter studies. Clin Transplant 2004; 18:446–9.
Sanchez-Fructuoso A, Conesa J, Perez Flores I, Ridao N, Calvo N, Prats D, Rodriguez A, Barrientos A. Conversion to sirolimus in renal transplant patients with tumors. Transplant Proc 2006; 38:2451–2.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
de Gruijl, F.R., Voskamp, P. (2009). Photocarcinogenesis – DNA Damage and Gene Mutations. In: Stockfleth, E., Ulrich, C. (eds) Skin Cancer after Organ Transplantation. Cancer Treatment and Research, vol 146. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-78574-5_9
Download citation
DOI: https://doi.org/10.1007/978-0-387-78574-5_9
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-387-78573-8
Online ISBN: 978-0-387-78574-5
eBook Packages: MedicineMedicine (R0)