UV radiation and the skin

International Journal of Molecular Sciences

Volumn 14, Issue 6, 2013, Pages 12222-12248

  D'Orazio, John ^a   Jarrett, Stuart ^a   Amaro Ortiz, Alexandra ^a   Scott, Timothy ^a  

^a UNIVERSITY OF KENTUCKY   (United States)

Author keywords

Cancer; Carcinogenesis; Melanin; Melanocortin 1 receptor; Mutagenesis; Pigmentation; Skin; Ultraviolet radiation

Indexed keywords

MELANIN; MELANOCORTIN 1 RECEPTOR;

CANCER RISK; EXCISION REPAIR; GENE FUNCTION; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; HEREDITY; HUMAN; MELANOCORTIN 1 RECEPTOR GENE; MELANOGENESIS; OXIDATIVE STRESS; RADIATION EXPOSURE; RADIOSENSITIVITY; REVIEW; SIGNAL TRANSDUCTION; SKIN CANCER; SKIN COLOR; SKIN DISEASE; SKIN PENETRATION; SKIN PIGMENTATION; SKIN SENSITIVITY; ULTRAVIOLET RADIATION; XERODERMA PIGMENTOSUM; ANIMAL; METABOLISM; PATHOLOGY; RADIATION RESPONSE; SKIN; SKIN TUMOR;

ANIMALS; HUMANS; MELANINS; OXIDATIVE STRESS; SKIN; SKIN NEOPLASMS; SKIN PIGMENTATION; ULTRAVIOLET RAYS;

EID: 84879014065     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms140612222     Document Type: Review

References (207)

1. Elwood, J.M.; Jopson, J. Melanoma and sun exposure: An overview of published studies. Int. J. Cancer 1997, 73, 198-203.
2. Lowe, N.J. An overview of ultraviolet radiation, sunscreens, and photo-induced dermatoses. Dermatol. Clin. 2006, 24, 9-17.
3. Slominski, A.; Wortsman, J. Neuroendocrinology of the skin. Endocr. Rev. 2000, 21, 457-487.
4. Slominski, A.; Wortsman, J.; Luger, T.; Paus, R.; Solomon, S. Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress. Physiol. Rev. 2000, 80, 979-1020.
5. Fuchs, E. Scratching the surface of skin development. Nature 2007, 445, 834-842.
6. Slominski, A.T.; Zmijewski, M.A.; Skobowiat, C.; Zbytek, B.; Slominski, R.M.; Steketee, J.D. Sensing the environment: Regulation of local and global homeostasis by the skin's neuroendocrine system. Adv. Anat. Embryol. Cell. Biol. 2012, 212, v-115.
7. Fuchs, E.; Raghavan, S. Getting under the skin of epidermal morphogenesis. Nat. Rev. Genet. 2002, 3, 199-209.
8. Madison, K.C. Barrier function of the skin: -la raison d'etre of the epidermis. J. Invest. Dermatol. 2003, 121, 231-241.
9. Proksch, E.; Brandner, J.M.; Jensen, J.M. The skin: An indispensable barrier. Exp. Dermatol. 2008, 17, 1063-1072.
10. Slominski, A.; Tobin, D.J.; Shibahara, S.; Wortsman, J. Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol. Rev. 2004, 84, 1155-1228.
11. Nordlund, J.J. The melanocyte and the epidermal melanin unit: An expanded concept. Dermatol. Clin. 2007, 25, 271-281.
12. Slominski, A.; Wortsman, J.; Plonka, P.M.; Schallreuter, K.U.; Paus, R.; Tobin, D.J. Hair follicle pigmentation. J. Invest. Dermatol. 2005, 124, 13-21.
13. Scherer, D.; Kumar, R. Genetics of pigmentation in skin cancer-A review. Mutat. Res. 2010, 705, 141-153.
14. Jimbow, K.; Salopek, T.G.; Dixon, W.T.; Searles, G.E.; Yamada, K. The epidermal melanin unit in the pathophysiology of malignant melanoma. Am. J. Dermatopathol. 1991, 13, 179-188.
15. Joshi, P.G.; Nair, N.; Begum, G.; Joshi, N.B.; Sinkar, V.P.; Vora, S. Melanocyte-keratinocyte interaction induces calcium signalling and melanin transfer to keratinocytes. Pigment. Cell Res. 2007, 20, 380-384.
16. Cardinali, G.; Bolasco, G.; Aspite, N.; Lucania, G.; Lotti, L.V.; Torrisi, M.R.; Picardo, M. Melanosome transfer promoted by keratinocyte growth factor in light and dark skin-derived keratinocytes. J. Invest. Dermatol. 2008, 128, 558-567.
17. Yamaguchi, Y.; Hearing, V.J. Physiological factors that regulate skin pigmentation. Biofactors 2009, 35, 193-199.
18. Slominski, A.; Paus, R.; Schadendorf, D. Melanocytes as -sensory and regulatory cells in the epidermis. J. Theor. Biol. 1993, 164, 103-120.
19. Kalka, K.; Mukhtar, H.; Turowski-Wanke, A.; Merk, H. Biomelanin antioxidants in cosmetics: Assessment based on inhibition of lipid peroxidation. Skin Pharmacol. Appl. Skin Physiol. 2000, 13, 143-149.
20. Mackintosh, J.A. The antimicrobial properties of melanocytes, melanosomes and melanin and the evolution of black skin. J. Theor. Biol. 2001, 211, 101-113.
21. Meyskens, F.L.; Farmer, P.; Fruehauf, J.P. Redox regulation in human melanocytes and melanoma. Pigment. Cell Res. 2001, 14, 148-154.
22. Double, K.L.; Ben-Shachar, D.; Youdim, M.B.; Zecca, L.; Riederer, P.; Gerlach, M. Influence of neuromelanin on oxidative pathways within the human substantia nigra. Neurotoxicol. Teratol. 2002, 24, 621-628.
23. Herrling, T.; Jung, K.; Fuchs, J. The role of melanin as protector against free radicals in skin and its role as free radical indicator in hair. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2008, 69, 1429-1435.
24. Wang, A.; Marino, A.R.; Gasyna, Z.; Gasyna, E.; Norris, J. Photoprotection by porcine eumelanin against singlet oxygen production. Photochem. PhotoBiol. 2008, 84, 679-682.
25. Riley, P.A. Melanin. Int. J. Biochem. Cell. Biol. 1997, 29, 1235-1239.
26. Meredith, P.; Sarna, T. The physical and chemical properties of eumelanin. Pigment. Cell Res. 2006, 19, 572-594.
27. Slominski, A.; Paus, R. Are L-tyrosine and L-dopa hormone-like bioregulators? J. Theor. Biol. 1990, 143, 123-138.
28. Slominski, A. Neuroendocrine activity of the melanocyte. Exp. Dermatol. 2009, 18, 760-763.
29. Slominski, A.; Zmijewski, M.A.; Pawelek, J. L-tyrosine and L-dihydroxyphenylalanine as hormone-like regulators of melanocyte functions. Pigment. Cell Melanoma Res. 2012, 25, 14-27.
30. Ito, S.; Wakamatsu, K.; Ozeki, H. Chemical analysis of melanins and its application to the study of the regulation of melanogenesis. Pigment. Cell Res. 2000, 13, 103-109.
31. Vincensi, M.R.; d'Ischia, M.; Napolitano, A.; Procaccini, E.M.; Riccio, G.; Monfrecola, G.; Santoianni, P.; Prota, G. Phaeomelanin versus eumelanin as a chemical indicator of ultraviolet sensitivity in fair-skinned subjects at high risk for melanoma: A pilot study. Melanoma Res. 1998, 8, 53-58.
32. Benedetto, J.P.; Ortonne, J.P.; Voulot, C.; Khatchadourian, C.; Prota, G.; Thivolet, J. Role of thiol compounds in mammalian melanin pigmentation: Part I. Reduced and oxidized glutathione. J. Invest. Dermatol. 1981, 77, 402-405.
33. Benedetto, J.P.; Ortonne, J.P.; Voulot, C.; Khatchadourian, C.; Prota, G.; Thivolet, J. Role of thiol compounds in mammalian melanin pigmentation. II. Glutathione and related enzymatic activities. J. Invest. Dermatol. 1982, 79, 422-424.
34. Sealy, R.C.; Hyde, J.S.; Felix, C.C.; Menon, I.A.; Prota, G.; Swartz, H.M.; Persad, S.; Haberman, H.F. Novel free radicals in synthetic and natural pheomelanins: Distinction between dopa melanins and cysteinyldopa melanins by ESR spectroscopy. Proc. Natl. Acad. Sci. USA 1982, 79, 2885-2889.
35. Costantini, C.; d'Ischia, M.; Palumbo, A.; Prota, G. Photochemistry of 5-S-cysteinyldopa. Photochem. PhotoBiol. 1994, 60, 33-37.
36. Prota, G. Melanins, melanogenesis and melanocytes: Looking at their functional significance from the chemist's viewpoint. Pigment. Cell Res. 2000, 13, 283-293.
37. Mitra, D.; Luo, X.; Morgan, A.; Wang, J.; Hoang, M.P.; Lo, J.; Guerrero, C.R.; Lennerz, J.K.; Mihm, M.C.; Wargo, J.A. et al. An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the red hair/fair skin background. Nature 2012, 491, 449-453.
38. Lu, H.; Edwards, C.; Gaskell, S.; Pearse, A.; Marks, R. Melanin content and distribution in the surface corneocyte with skin phototypes. Br. J. Dermatol. 1996, 135, 263-267.
39. Andreassi, L.; Flori, M.L.; Rubegni, P. Sun and skin-Role of phototype and skin colour. Rheumaderm 1999, 455, 469-475.
40. Kawada, A. Risk and preventive factors for skin phototype. J. Dermatol. Sci. 2000, 23, S27-S29.
41. Ravnbak, M.H. Objective determination of Fitzpatrick skin type. Dan. Med. Bull. 2010, 57, B4153.
42. Godar, D.E. UV doses worldwide. Photochem. PhotoBiol. 2005, 81, 736-749.
43. Dore, J.F.; Chignol, M.C. Tanning salons and skin cancer. Photochem. PhotoBiol. Sci. 2012, 11, 30-37.
44. Elwood, J.M.; Diffey, B.L. A consideration of ambient solar ultraviolet radiation in the interpretation of studies of the aetiology of melanoma. Melanoma Res. 1993, 3, 113-122.
45. Tatalovich, Z.; Wilson, J.P.; Mack, T.; Yan, Y.; Cockburn, M. The objective assessment of lifetime cumulative ultraviolet exposure for determining melanoma risk. J. Photochem. PhotoBiol. B 2006, 85, 198-204.
46. Qureshi, A.A.; Laden, F.; Colditz, G.A.; Hunter, D.J. Geographic variation and risk of skin cancer in US women. Differences between melanoma, squamous cell carcinoma, and basal cell carcinoma. Arch. Intern. Med. 2008, 168, 501-507.
47. Choi, K.; Lazovich, D.; Southwell, B.; Forster, J.; Rolnick, S.J.; Jackson, J. Prevalence and characteristics of indoor tanning use among men and women in the United States. Arch. Dermatol. 2010, 146, 1356-1361.
48. Hornung, R.L.; Magee, K.H.; Lee, W.J.; Hansen, L.A.; Hsieh, Y.C. Tanning facility use: Are we exceeding food and drug administration limits? J. Am. Acad. Dermatol. 2003, 49, 655-661.
49. Nilsen, L.T.; Aalerud, T.N.; Hannevik, M.; Veierod, M.B. UVB and UVA irradiances from indoor tanning devices. Photochem. PhotoBiol. Sci. 2011, 10, 1129-1136.
50. Nolan, B.V.; Feldman, S.R. Ultraviolet tanning addiction. Dermatol. Clin. 2009, 27, 109-112.
51. Kourosh, A.S.; Harrington, C.R.; Adinoff, B. Tanning as a behavioral addiction. Am. J. Drug Alcohol. Abuse 2010, 36, 284-290.
52. Harrington, C.R.; Beswick, T.C.; Leitenberger, J.; Minhajuddin, A.; Jacobe, H.T.; Adinoff, B. Addictive-like behaviours to ultraviolet light among frequent indoor tanners. Clin. Exp. Dermatol. 2011, 36, 33-38.
53. Poorsattar, S.P.; Hornung, R.L. UV light abuse and high-risk tanning behavior among undergraduate college students. J. Am. Acad. Dermatol. 2007, 56, 375-379.
54. Karagas, M.R.; Stannard, V.A.; Mott, L.A.; Slattery, M.J.; Spencer, S.K.; Weinstock, M.A. Use of tanning devices and risk of basal cell and squamous cell skin cancers. J. Natl. Cancer Inst. 2002, 94, 224-226.
55. Levine, J.A.; Sorace, M.; Spencer, J.; Siegel, D.M. The indoor UV tanning industry: A review of skin cancer risk, health benefit claims, and regulation. J. Am. Acad. Dermatol. 2005, 53, 1038-1044.
56. Schulman, J.M.; Fisher, D.E. Indoor ultraviolet tanning and skin cancer: Health risks and opportunities. Curr. Opin. Oncol. 2009, 21, 144-149.
57. Fisher, D.E.; James, W.D. Indoor tanning-Science, behavior, and policy. N. Eng. J. Med. 2010, 363, 901-903.
58. Weinstock, M.A.; Fisher, D.E. Indoor ultraviolet tanning: What the data do and do not show regarding risk of melanoma and keratinocyte malignancies. J. Natl. Compr. Canc. Netw. 2010, 8, 867-873.
59. Han, J.; Colditz, G.A.; Hunter, D.J. Risk factors for skin cancers: A nested case-control study within the Nurses' Health Study. Int. J. Epidemiol. 2006, 35, 1514-1521.
60. Lazovich, D.; Vogel, R.I.; Berwick, M.; Weinstock, M.A.; Anderson, K.E.; Warshaw, E.M. Indoor tanning and risk of melanoma: A case-control study in a highly exposed population. Cancer Epidemiol. Biomark. Prev. 2010, 19, 1557-1568.
61. Holick, M.F. Sunlight -Dilemma: Risk of skin cancer or bone disease and muscle weakness. Lancet 2001, 357, 4-6.
62. Holick, M. Does sunscreen block the skin's ability to make vitamin D? If so, how can I get enough of this vitamin without raising my risk of skin cancer? Health News 2002, 8, 12.
63. Tangpricha, V.; Turner, A.; Spina, C.; Decastro, S.; Chen, T.C.; Holick, M.F. Tanning is associated with optimal vitamin D status (serum 25-hydroxyvitamin D concentration) and higher bone mineral density. Am. J. Clin. Nutr. 2004, 80, 1645-1649.
64. Holick, M.F. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am. J. Clin. Nutr. 2004, 80, 1678S-1688S.
65. Rajakumar, K.; Greenspan, S.L.; Thomas, S.B.; Holick, M.F. SOLAR ultraviolet radiation and vitamin D: A historical perspective. Am. J. Public Health 2007, 97, 1746-1754.
66. Holick, M.F.; Chen, T.C.; Lu, Z.; Sauter, E. Vitamin D and skin physiology: A D-lightful story. J. Bone Miner. Res. 2007, 22, V28-V33.
67. Holick, M.F. Sunlight, UV-radiation, vitamin D and skin cancer: How much sunlight do we need? Adv. Exp. Med. Biol. 2008, 624, 1-15.
68. Holick, M.F. Vitamin D and sunlight: Strategies for cancer prevention and other health benefits. Clin. J. Am. Soc. Nephrol. 2008, 3, 1548-1554.
69. Carbone, L.D.; Rosenberg, E.W.; Tolley, E.A.; Holick, M.F.; Hughes, T.A.; Watsky, M.A.; Barrow, K.D.; Chen, T.C.; Wilkin, N.K.; Bhattacharya, S.K. et al. 25-Hydroxyvitamin D, cholesterol, and ultraviolet irradiation. Metabolism 2008, 57, 741-748.
70. Holick, M.F. Vitamin D: A millenium perspective. J. Cell. Biochem. 2003, 88, 296-307.
71. Holick, M.F. Resurrection of vitamin D deficiency and rickets. J. Clin. Investig. 2006, 116, 2062-2072.
72. Holick, M.F.; Chen, T.C. Vitamin D deficiency: A worldwide problem with health consequences. Am. J. Clin. Nutr. 2008, 87, 1080S-1086S.
73. Reichrath, J.; Nurnberg, B. Cutaneous vitamin D synthesis versus skin cancer development: The Janus faces of solar UV-radiation. Dermatoendocrinology 2009, 1, 253-261.
74. Gallagher, R.P.; Lee, T.K.; Bajdik, C.D.; Borugian, M. Ultraviolet radiation. Chronic. Dis. Can. 2010, 29, 51-68.
75. Lucas, R.M.; McMichael, A.J.; Armstrong, B.K.; Smith, W.T. Estimating the global disease burden due to ultraviolet radiation exposure. Int. J. Epidemiol. 2008, 37, 654-667.
76. Clydesdale, G.J.; Dandie, G.W.; Muller, H.K. Ultraviolet light induced injury: Immunological and inflammatory effects. Immunol. Cell. Biol. 2001, 79, 547-568.
77. Matsumura, Y.; Ananthaswamy, H.N. Toxic effects of ultraviolet radiation on the skin. Toxicol. Appl. Pharmacol. 2004, 195, 298-308.
78. Skobowiat, C.; Dowdy, J.C.; Sayre, R.M.; Tuckey, R.C.; Slominski, A. Cutaneous hypothalamic-pituitary-adrenal axis homolog: Regulation by ultraviolet radiation. Am. J. Physiol. Endocrinol. Metab. 2011, 301, E484-E493.
79. Skobowiat, C.; Sayre, R.M.; Dowdy, J.C.; Slominski, A.T. Ultraviolet radiation regulates cortisol activity in a waveband-dependent manner in human skin ex vivo. Br. J. Dermatol. 2013, 168, 595-601.
80. Bayerl, C.; Taake, S.; Moll, I.; Jung, E.G. Characterization of sunburn cells after exposure to ultraviolet light. PhotoDermatol. Photoimmunol. Photomed. 1995, 11, 149-154.
81. Coelho, S.G.; Choi, W.; Brenner, M.; Miyamura, Y.; Yamaguchi, Y.; Wolber, R.; Smuda, C.; Batzer, J.; Kolbe, L.; Ito, S. et al. Short- and long-term effects of UV radiation on the pigmentation of human skin. J. Investig. Dermatol. Symp. Proc. 2009, 14, 32-35.
82. Scott, T.L.; Christian, P.A.; Kesler, M.V.; Donohue, K.M.; Shelton, B.; Wakamatsu, K.; Ito, S.; D'Orazio, J. Pigment-independent cAMP-mediated epidermal thickening protects against cutaneous UV injury by keratinocyte proliferation. Exp. Dermatol. 2012, 21, 771-777.
83. Slominski, A.; Wortsman, J.; Pisarchik, A.; Zbytek, B.; Linton, E.A.; Mazurkiewicz, J.E.; Wei, E.T. Cutaneous expression of corticotropin-releasing hormone (CRH), urocortin, and CRH receptors. FASEB J. 2001, 15, 1678-1693.
84. D'Orazio, J.A.; Nobuhisa, T.; Cui, R.; Arya, M.; Spry, M.; Wakamatsu, K.; Igras, V.; Kunisada, T.; Granter, S.R.; Nishimura, E.K. et al. Topical drug rescue strategy and skin protection based on the role of Mc1r in UV-induced tanning. Nature 2006, 443, 340-344.
85. Slominski, A.; Wortsman, J.; Tuckey, R.C.; Paus, R. Differential expression of HPA axis homolog in the skin. Mol. Cell. Endocrinol. 2007, 265-266, 143-149.
86. Cui, R.; Widlund, H.R.; Feige, E.; Lin, J.Y.; Wilensky, D.L.; Igras, V.E.; D'Orazio, J.; Fung, C.Y.; Schanbacher, C.F.; Granter, S.R. et al. Central role of p53 in the Suntan response and pathologic hyperpigmentation. Cell 2007, 128, 853-864.
87. McGill, G.G.; Horstmann, M.; Widlund, H.R.; Du, J.; Motyckova, G.; Nishimura, E.K.; Lin, Y.L.; Ramaswamy, S.; Avery, W.; Ding, H.F. et al. Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability. Cell 2002, 109, 707-718.
88. Widlund, H.R.; Fisher, D.E. Microphthalamia-associated transcription factor: A critical regulator of pigment cell development and survival. Oncogene 2003, 22, 3035-3041.
89. Rouzaud, F.; Costin, G.E.; Yamaguchi, Y.; Valencia, J.C.; Berens, W.F.; Chen, K.G.; Hoashi, T.; Bohm, M.; Abdel-Malek, Z.A.; Hearing, V.J. Regulation of constitutive and UVR-induced skin pigmentation by melanocortin 1 receptor isoforms. FASEB J. 2006, 20, 1927-1929.
90. Levy, C.; Khaled, M.; Fisher, D.E. MITF: Master regulator of melanocyte development and melanoma oncogene. Trends Mol. Med. 2006, 12, 406-414.
91. Mitra, D.; Fisher, D.E. Transcriptional regulation in melanoma. Hematol. Oncol. Clin. N. Am. 2009, 23, 447-465.
92. Park, S.B.; Huh, C.H.; Choe, Y.B.; Youn, J.I. Time course of ultraviolet-induced skin reactions evaluated by two different reflectance spectrophotometers: DermaSpectrophotometer and Minolta spectrophotometer CM-2002. PhotoDermatol. Photoimmunol. Photomed. 2002, 18, 23-28.
93. Beattie, P.E.; Dawe, R.S.; Ferguson, J.; Ibbotson, S.H. Dose-response and time-course characteristics of UV-A1 erythema. Arch. Dermatol. 2005, 141, 1549-1555.
94. Chedekel, M.R.; Zeise, L. Sunlight, melanogenesis and radicals in the skin. Lipids 1988, 23, 587-591.
95. Pawelek, J.M.; Chakraborty, A.K.; Osber, M.P.; Orlow, S.J.; Min, K.K.; Rosenzweig, K.E.; Bolognia, J.L. Molecular cascades in UV-induced melanogenesis: A central role for melanotropins? Pigment. Cell Res. 1992, 5, 348-356.
96. Eller, M.S.; Ostrom, K.; Gilchrest, B.A. DNA damage enhances melanogenesis. Proc. Natl. Acad. Sci. USA 1996, 93, 1087-1092.
97. Gilchrest, B.A.; Park, H.Y.; Eller, M.S.; Yaar, M. Mechanisms of ultraviolet light-induced pigmentation. Photochem. PhotoBiol. 1996, 63, 1-10.
98. Funasaka, Y.; Chakraborty, A.K.; Hayashi, Y.; Komoto, M.; Ohashi, A.; Nagahama, M.; Inoue, Y.; Pawelek, J.; Ichihashi, M. Modulation of melanocyte-stimulating hormone receptor expression on normal human melanocytes: Evidence for a regulatory role of ultraviolet B, interleukin-1alpha, interleukin-1beta, endothelin-1 and tumour necrosis factor-alpha. Br. J. Dermatol. 1998, 139, 216-224.
99. Duval, C.; Regnier, M.; Schmidt, R. Distinct melanogenic response of human melanocytes in mono-culture, in co-culture with keratinocytes and in reconstructed epidermis, to UV exposure. Pigment. Cell Res. 2001, 14, 348-355.
100. Raffin-Sanson, M.L.; de Keyzer, Y.; Bertagna, X. Proopiomelanocortin, a polypeptide precursor with multiple functions: From physiology to pathological conditions. Eur. J. Endocrinol. 2003, 149, 79-90.
101. Corre, S.; Primot, A.; Sviderskaya, E.; Bennett, D.C.; Vaulont, S.; Goding, C.R.; Galibert, M.D. UV-induced expression of key component of the tanning process, the POMC and MC1R genes, is dependent on the p-38-activated upstream stimulating factor-1 (USF-1). J. Biol. Chem. 2004, 279, 51226-51233.
102. Slominski, A.; Tobin, D.J.; Paus, R. Does p53 regulate skin pigmentation by controlling proopiomelanocortin gene transcription? Pigment. Cell Res. 2007, 20, 307-308.
103. Kripke, M.L.; Fisher, M.S. Immunologic parameters of ultraviolet carcinogenesis. J. Natl. Cancer Inst. 1976, 57, 211-215.
104. Kripke, M.L.; Lofgreen, J.S.; Beard, J.; Jessup, J.M.; Fisher, M.S. In vivo immune responses of mice during carcinogenesis by ultraviolet irradiation. J. Natl. Cancer Inst. 1977, 59, 1227-1230.
105. Kripke, M.L. Effects of UV radiation on the immune system: Consequences for UV carcinogenesis. Adv. Exp. Med. Biol. 1979, 121, 589-598.
106. Kripke, M.L. Immunological unresponsiveness induced by ultraviolet radiation. Immunol. Rev. 1984, 80, 87-102.
107. Schade, N.; Esser, C.; Krutmann, J. Ultraviolet B radiation-induced immunosuppression: Molecular mechanisms and cellular alterations. Photochem. PhotoBiol. Sci. 2005, 4, 699-708.
108. Norval, M. The mechanisms and consequences of ultraviolet-induced immunosuppression. Prog. Biophys. Mol. Biol. 2006, 92, 108-118.
109. De Gruijl, F.R. UV-induced immunosuppression in the balance. Photochem. PhotoBiol. 2008, 84, 2-9.
110. Kripke, M.L. Reflections on the field of photoimmunology. J. Invest. Dermatol. 2013, 133, 27-30.
111. Polefka, T.G.; Meyer, T.A.; Agin, P.P.; Bianchini, R.J. Effects of solar radiation on the skin. J. Cosmet. Dermatol. 2012, 11, 134-143.
112. Sklar, L.R.; Almutawa, F.; Lim, H.W.; Hamzavi, I. Effects of ultraviolet radiation, visible light, and infrared radiation on erythema and pigmentation: A review. Photochem. PhotoBiol. Sci. 2013, 12, 54-64.
113. Pfeifer, G.P.; You, Y.H.; Besaratinia, A. Mutations induced by ultraviolet light. Mutat. Res. 2005, 571, 19-31.
114. Tyrrell, R.M. Ultraviolet radiation and free radical damage to skin. Biochem. Soc. Symp. 1995, 61, 47-53.
115. Sander, C.S.; Chang, H.; Hamm, F.; Elsner, P.; Thiele, J.J. Role of oxidative stress and the antioxidant network in cutaneous carcinogenesis. Int. J. Dermatol. 2004, 43, 326-335.
116. Burke, K.E. Photoaging: The role of oxidative stress. G Ital. Dermatol. Venereol. 2010, 145, 445-459.
117. De Gruijl, F.R. Photocarcinogenesis: UVA vs. UVB. Methods Enzymol. 2000, 319, 359-366.
118. Ikehata, H.; Ono, T. The mechanisms of UV mutagenesis. J. Radiat. Res. 2011, 52, 115-125.
119. Sage, E.; Girard, P.M.; Francesconi, S. Unravelling UVA-induced mutagenesis. Photochem. PhotoBiol. Sci. 2012, 11, 74-80.
120. Schulz, I.; Mahler, H.C.; Boiteux, S.; Epe, B. Oxidative DNA base damage induced by singlet oxygen and photosensitization: Recognition by repair endonucleases and mutagenicity. Mutat. Res. 2000, 461, 145-156.
121. Nishimura, S. Involvement of mammalian OGG1(MMH) in excision of the 8-hydroxyguanine residue in DNA. Free Radic. Biol. Med. 2002, 32, 813-821.
122. Kunisada, M.; Sakumi, K.; Tominaga, Y.; Budiyanto, A.; Ueda, M.; Ichihashi, M.; Nakabeppu, Y.; Nishigori, C. 8-Oxoguanine formation induced by chronic UVB exposure makes Ogg1 knockout mice susceptible to skin carcinogenesis. Cancer Res. 2005, 65, 6006-6010.
123. Agar, N.S.; Halliday, G.M.; Barnetson, R.S.; Ananthaswamy, H.N.; Wheeler, M.; Jones, A.M. The basal layer in human squamous tumors harbors more UVA than UVB fingerprInt. mutations: A role for UVA in human skin carcinogenesis. Proc. Natl. Acad. Sci. USA 2004, 101, 4954-4959.
124. Schallreuter, K.U.; Moore, J.; Wood, J.M.; Beazley, W.D.; Gaze, D.C.; Tobin, D.J.; Marshall, H.S.; Panske, A.; Panzig, E.; Hibberts, N.A. In vivo and in vitro evidence for hydrogen peroxide (H2O2) accumulation in the epidermis of patients with vitiligo and its successful removal by a UVB-activated pseudocatalase. J. Investig. Dermatol. Symp. Proc. 1999, 4, 91-96.
125. Song, X.; Mosby, N.; Yang, J.; Xu, A.; Abdel-Malek, Z.; Kadekaro, A.L. Alpha-MSH activates immediate defense responses to UV-induced oxidative stress in human melanocytes. Pigment. Cell Melanoma Res. 2009, 22, 809-818.
126. Kadekaro, A.L.; Chen, J.; Yang, J.; Chen, S.; Jameson, J.; Swope, V.B.; Cheng, T.; Kadakia, M.; Abdel-Malek, Z. Alpha-melanocyte-stimulating hormone suppresses oxidative stress through a p53-mediated signaling pathway in human melanocytes. Mol. Cancer Res. 2012, 10, 778-786.
127. Krol, E.S.; Kramer-Stickland, K.A.; Liebler, D.C. Photoprotective actions of topically applied vitamin E. Drug Metab. Rev. 2000, 32, 413-420.
128. Bickers, D.R.; Athar, M. Oxidative stress in the pathogenesis of skin disease. J. Invest. Dermatol. 2006, 126, 2565-2575.
129. Kokot, A.; Metze, D.; Mouchet, N.; Galibert, M.D.; Schiller, M.; Luger, T.A.; Bohm, M. Alpha-melanocyte-stimulating hormone counteracts the suppressive effect of UVB on Nrf2 and Nrf-dependent gene expression in human skin. Endocrinology 2009, 150, 3197-3206.
130. Cleaver, J.E.; Crowley, E. UV damage, DNA repair and skin carcinogenesis. Front. BioSci. 2002, 7, d1024-d1043.
131. Wei, Q.; Lee, J.E.; Gershenwald, J.E.; Ross, M.I.; Mansfield, P.F.; Strom, S.S.; Wang, L.E.; Guo, Z.; Qiao, Y.; Amos, C.I. et al. Repair of UV light-induced DNA damage and risk of cutaneous malignant melanoma. J. Natl. Cancer Inst. 2003, 95, 308-315.
132. Sarasin, A. The molecular pathways of ultraviolet-induced carcinogenesis. Mutat. Res. 1999, 428, 5-10.
133. Hoeijmakers, J.H. DNA damage, aging, and cancer. N. Eng. J. Med. 2009, 361, 1475-1485.
134. Kanjilal, S.; Pierceall, W.E.; Cummings, K.K.; Kripke, M.L.; Ananthaswamy, H.N. High frequency of p53 mutations in ultraviolet radiation-induced murine skin tumors: Evidence for strand bias and tumor heterogeneity. Cancer Res. 1993, 53, 2961-2964.
135. Sato, M.; Nishigori, C.; Zghal, M.; Yagi, T.; Takebe, H. Ultraviolet-specific mutations in p53 gene in skin tumors in xeroderma pigmentosum patients. Cancer Res. 1993, 53, 2944-2946.
136. Daya-Grosjean, L.; Dumaz, N.; Sarasin, A. The specificity of p53 mutation spectra in sunlight induced human cancers. J. Photochem. PhotoBiol. B 1995, 28, 115-124.
137. Hodis, E.; Watson, I.R.; Kryukov, G.V.; Arold, S.T.; Imielinski, M.; Theurillat, J.P.; Nickerson, E.; Auclair, D.; Li, L.; Place, C. et al. A landscape of driver mutations in melanoma. Cell 2012, 150, 251-263.
138. Nouspikel, T. DNA repair in mammalian cells: Nucleotide excision repair: Variations on versatility. Cell. Mol. Life Sci. 2009, 66, 994-1009.
139. DiGiovanna, J.J.; Kraemer, K.H. Shining a light on xeroderma pigmentosum. J. Invest. Dermatol. 2012, 132, 785-796.
140. Daya-Grosjean, L. Xeroderma pigmentosum and skin cancer. Adv. Exp. Med. Biol. 2008, 637, 19-27.
141. Sancar, A.; Lindsey-Boltz, L.A.; Unsal-Kacmaz, K.; Linn, S. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Ann. Rev. Biochem. 2004, 73, 39-85.
142. Reed, S.H. Nucleotide excision repair in chromatin: The shape of things to come. DNA Repair 2005, 4, 909-918.
143. Leibeling, D.; Laspe, P.; Emmert, S. Nucleotide excision repair and cancer. J. Mol. Histol. 2006, 37, 225-238.
144. Rogers, H.W.; Weinstock, M.A.; Harris, A.R.; Hinckley, M.R.; Feldman, S.R.; Fleischer, A.B.; Coldiron, B.M. Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch. Dermatol. 2010, 146, 283-287.
145. Donaldson, M.R.; Coldiron, B.M. No end in sight: The skin cancer epidemic continues. Semin. Cutan. Med. Surg. 2011, 30, 3-5.
146. De Gruijl, F.R. Skin cancer and solar UV radiation. Eur. J. Cancer 1999, 35, 2003-2009.
147. Chen, J.G.; Fleischer, A.B.; Smith, E.D.; Kancler, C.; Goldman, N.D.; Williford, P.M.; Feldman, S.R. Cost of nonmelanoma skin cancer treatment in the United States. Dermatol. Surg. 2001, 27, 1035-1038.
148. Narayanan, D.L.; Saladi, R.N.; Fox, J.L. Ultraviolet radiation and skin cancer. Int. J. Dermatol. 2010, 49, 978-986.
149. Berwick, M.; Wiggins, C. The current epidemiology of cutaneous malignant melanoma. Front. BioSci. 2006, 11, 1244-1254.
150. Croyle, R.T. SEER Stat Fact Sheets: Melanoma of the Skin. Available online: http://www.seer.cancer.gov/statfacts/html/melan.html#incidence-mortality (accessed on 4 March 2013).
151. Marks, R. Epidemiology of melanoma. Clin. Exp. Dermatol. 2000, 25, 459-463.
152. Flaherty, K.T.; Puzanov, I.; Kim, K.B.; Ribas, A.; McArthur, G.A.; Sosman, J.A.; O'Dwyer, P.J.; Lee, R.J.; Grippo, J.F.; Nolop, K. et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N. Eng. J. Med. 2010, 363, 809-819.
153. Sosman, J.A.; Kim, K.B.; Schuchter, L.; Gonzalez, R.; Pavlick, A.C.; Weber, J.S.; McArthur, G.A.; Hutson, T.E.; Moschos, S.J.; Flaherty, K.T. et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N. Eng. J. Med. 2012, 366, 707-714.
154. Nikolaou, V.A.; Stratigos, A.J.; Flaherty, K.T.; Tsao, H. Melanoma: New insights and new therapies. J. Invest. Dermatol. 2012, 132, 854-863.
155. Ji, Z.; Flaherty, K.T.; Tsao, H. Targeting the RAS pathway in melanoma. Trends Mol. Med. 2012, 18, 27-35.
156. Flaherty, K.T. Targeting metastatic melanoma. Annu. Rev. Med. 2012, 63, 171-183.
157. Hodi, F.S.; Oble, D.A.; Drappatz, J.; Velazquez, E.F.; Ramaiya, N.; Ramakrishna, N.; Day, A.L.; Kruse, A.; Mac Rae, S.; Hoos, A. et al. CTLA-4 blockade with ipilimumab induces significant clinical benefit in a female with melanoma metastases to the CNS. Nat. Clin. Pract. Oncol. 2008, 5, 557-561.
158. Hodi, F.S.; O'Day, S.J.; McDermott, D.F.; Weber, R.W.; Sosman, J.A.; Haanen, J.B.; Gonzalez, R.; Robert, C.; Schadendorf, D.; Hassel, J.C. et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Eng. J. Med. 2010, 363, 711-723.
159. Franceschi, S.; Cristofolini, M. Cutaneous malignant melanoma: Epidemiological considerations. Semin. Surg. Oncol. 1992, 8, 345-352.
160. Rivers, J.K. The detection and management of dysplastic nevi and early melanoma. World J. Surg. 1992, 16, 166-172.
161. Garland, C.F.; Garland, F.C.; Gorham, E.D. Rising trends in melanoma. An hypothesis concerning sunscreen effectiveness. Ann. Epidemiol. 1993, 3, 103-110.
162. Boyle, P.; Maisonneuve, P.; Dore, J.F. Epidemiology of malignant melanoma. Br. Med. Bull. 1995, 51, 523-547.
163. Liu, T.; Soong, S.J. Epidemiology of malignant melanoma. Surg. Clin. N. Am. 1996, 76, 1205-1222.
164. Weinstock, M.A. Issues in the epidemiology of melanoma. Hematol. Oncol. Clin. N. Am. 1998, 12, 681-698.
165. Brochez, L.; Naeyaert, J.M. Understanding the trends in melanoma incidence and mortality: Where do we stand? Eur. J. Dermatol. 2000, 10, 71-75.
166. Diepgen, T.L.; Mahler, V. The epidemiology of skin cancer. Br. J. Dermatol. 2002, 146, 1-6.
167. Rigel, D.S. The effect of sunscreen on melanoma risk. Dermatol. Clin. 2002, 20, 601-606.
168. Weinstock, M.A. Cutaneous melanoma: Public health approach to early detection. Dermatol. Ther. 2006, 19, 26-31.
169. Norval, M.; Cullen, A.P.; de Gruijl, F.R.; Longstreth, J.; Takizawa, Y.; Lucas, R.M.; Noonan, F.P.; van der Leun, J.C. The effects on human health from stratospheric ozone depletion and its interactions with climate change. Photochem. PhotoBiol. Sci. 2007, 6, 232-251.
170. Leiter, U.; Garbe, C. Epidemiology of melanoma and nonmelanoma skin cancer-The role of sunlight. Adv. Exp. Med. Biol. 2008, 624, 89-103.
171. Tucker, M.A. Melanoma epidemiology. Hematol. Oncol. Clin. N. Am. 2009, 23, 383-395.
172. Norval, M.; Lucas, R.M.; Cullen, A.P.; de Gruijl, F.R.; Longstreth, J.; Takizawa, Y.; van der Leun, J.C. The human health effects of ozone depletion and interactions with climate change. Photochem. PhotoBiol. Sci. 2011, 10, 199-225.
173. Linos, E.; Swetter, S.M.; Cockburn, M.G.; Colditz, G.A.; Clarke, C.A. Increasing burden of melanoma in the United States. J. Invest. Dermatol. 2009, 129, 1666-1674.
174. Armstrong, B.K.; Kricker, A. How much melanoma is caused by sun exposure? Melanoma Res. 1993, 3, 395-401.
175. Pleasance, E.D.; Cheetham, R.K.; Stephens, P.J.; McBride, D.J.; Humphray, S.J.; Greenman, C.D.; Varela, I.; Lin, M.L.; Ordonez, G.R.; Bignell, G.R. et al. A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 2010, 463, 191-196.
176. Ling, G.; Persson, A.; Berne, B.; Uhlen, M.; Lundeberg, J.; Ponten, F. Persistent p53 mutations in single cells from normal human skin. Am. J. Pathol. 2001, 159, 1247-1253.
177. Lacour, J.P. Carcinogenesis of basal cell carcinomas: Genetics and molecular mechanisms. Br. J. Dermatol. 2002, 146, 17-19.
178. Bolshakov, S.; Walker, C.M.; Strom, S.S.; Selvan, M.S.; Clayman, G.L.; El-Naggar, A.; Lippman, S.M.; Kripke, M.L.; Ananthaswamy, H.N. p53 mutations in human aggressive and nonaggressive basal and squamous cell carcinomas. Clin. Cancer Res. 2003, 9, 228-234.
179. Reifenberger, J.; Wolter, M.; Knobbe, C.B.; Kohler, B.; Schonicke, A.; Scharwachter, C.; Kumar, K.; Blaschke, B.; Ruzicka, T.; Reifenberger, G. Somatic mutations in the PTCH, SMOH, SUFUH and TP53 genes in sporadic basal cell carcinomas. Br. J. Dermatol. 2005, 152, 43-51.
180. Daya-Grosjean, L.; Sarasin, A. The role of UV induced lesions in skin carcinogenesis: An overview of oncogene and tumor suppressor gene modifications in xeroderma pigmentosum skin tumors. Mutat. Res. 2005, 571, 43-56.
181. Queille, S.; Luron, L.; Spatz, A.; Avril, M.F.; Ribrag, V.; Duvillard, P.; Hiesse, C.; Sarasin, A.; Armand, J.P.; 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, 724-731.
182. Benjamin, C.L.; Melnikova, V.O.; Ananthaswamy, H.N. P53 protein and pathogenesis of melanoma and nonmelanoma skin cancer. Adv. Exp. Med. Biol. 2008, 624, 265-282.
183. Beissert, S.; Loser, K. Molecular and cellular mechanisms of photocarcinogenesis. Photochem. PhotoBiol. 2008, 84, 29-34.
184. Rees, J.L. The genetics of sun sensitivity in humans. Am. J. Hum. Genet. 2004, 75, 739-751.
185. Valverde, P.; Healy, E.; Jackson, I.; Rees, J.L.; Thody, A.J. Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans. Nat. Genet. 1995, 11, 328-330.
186. Valverde, P.; Healy, E.; Sikkink, S.; Haldane, F.; Thody, A.J.; Carothers, A.; Jackson, I.J.; Rees, J.L. The Asp84Glu variant of the melanocortin 1 receptor (MC1R) is associated with melanoma. Hum. Mol. Genet. 1996, 5, 1663-1666.
187. Koppula, S.V.; Robbins, L.S.; Lu, D.; Baack, E.; White, C.R.; Swanson, N.A.; Cone, R.D. Identification of common polymorphisms in the coding sequence of the human MSH receptor (MCIR) with possible biological effects. Hum. Mutat. 1997, 9, 30-36.
188. Rees, J.L.; Healy, E. Melanocortin receptors, red hair, and skin cancer. J. Investig. Dermatol. Symp. Proc. 1997, 2, 94-98.
189. Abdel-Malek, Z.A.; Kadekaro, A.L.; Kavanagh, R.J.; Todorovic, A.; Koikov, L.N.; McNulty, J.C.; Jackson, P.J.; Millhauser, G.L.; Schwemberger, S.; Babcock, G. et al. Melanoma prevention strategy based on using tetrapeptide alpha-MSH analogs that protect human melanocytes from UV-induced DNA damage and cytotoxicity. FASEB J. 2006, 20, 1561-1563.
190. Landi, M.T.; Bauer, J.; Pfeiffer, R.M.; Elder, D.E.; Hulley, B.; Minghetti, P.; Calista, D.; Kanetsky, P.A.; Pinkel, D.; Bastian, B.C. MC1R germline variants confer risk for BRAF-mutant melanoma. Science Signal. 2006, 313, 521.
191. Roberts, D.W.; Newton, R.A.; Leonard, J.H.; Sturm, R.A. Melanocytes expressing MC1R polymorphisms associated with red hair color have altered MSH-ligand activated pigmentary responses in coculture with keratinocytes. J. Cell. Physiol. 2008, 215, 344-355.
192. Abdel-Malek, Z.A.; Ruwe, A.; Kavanagh-Starner, R.; Kadekaro, A.L.; Swope, V.; Haskell-Luevano, C.; Koikov, L.; Knittel, J.J. Alpha-MSH tripeptide analogs activate the melanocortin 1 receptor and reduce UV-induced DNA damage in human melanocytes. Pigment. Cell Melanoma Res. 2009, 22, 635-644.
193. Suzuki, I.; Cone, R.D.; Im, S.; Nordlund, J.; Abdel-Malek, Z.A. Binding of melanotropic hormones to the melanocortin receptor MC1R on human melanocytes stimulates proliferation and melanogenesis. Endocrinology 1996, 137, 1627-1633.
194. Sturm, R.A.; Duffy, D.L.; Box, N.F.; Newton, R.A.; Shepherd, A.G.; Chen, W.; Marks, L.H.; Leonard, J.H.; Martin, N.G. Genetic association and cellular function of MC1R variant alleles in human pigmentation. Ann. N. Y. Acad. Sci. 2003, 994, 348-358.
195. Kadekaro, A.L.; Kanto, H.; Kavanagh, R.; Abdel-Malek, Z.A. Significance of the melanocortin 1 receptor in regulating human melanocyte pigmentation, proliferation, and survival. Ann. N. Y. Acad. Sci. 2003, 994, 359-365.
196. Bertolotto, C.; Abbe, P.; Hemesath, T.J.; Bille, K.; Fisher, D.E.; Ortonne, J.P.; Ballotti, R. Microphthalmia gene product as a signal transducer in cAMP-induced differentiation of melanocytes. J. Cell. Biol. 1998, 142, 827-835.
197. Newton, R.A.; Roberts, D.W.; Leonard, J.H.; Sturm, R.A. Human melanocytes expressing MC1R variant alleles show impaired activation of multiple signaling pathways. Peptides 2007, 28, 2387-2396.
198. Hauser, J.E.; Kadekaro, A.L.; Kavanagh, R.J.; Wakamatsu, K.; Terzieva, S.; Schwemberger, S.; Babcock, G.; Rao, M.B.; Ito, S.; Abdel-Malek, Z.A. Melanin content and MC1R function independently affect UVR-induced DNA damage in cultured human melanocytes. Pigment. Cell Res. 2006, 19, 303-314.
199. Sturm, R.A. Skin colour and skin cancer-MC1R, the genetic link. Melanoma Res. 2002, 12, 405-416.
200. Beaumont, K.A.; Shekar, S.N.; Cook, A.L.; Duffy, D.L.; Sturm, R.A. Red hair is the null phenotype of MC1R. Hum. Mutat. 2008, 29, E88-E94.
201. Landi, M.T.; Kanetsky, P.A.; Tsang, S.; Gold, B.; Munroe, D.; Rebbeck, T.; Swoyer, J.; Ter-Minassian, M.; Hedayati, M.; Grossman, L. et al. MC1R, ASIP, and DNA repair in sporadic and familial melanoma in a Mediterranean population. J. Natl. Cancer Inst. 2005, 97, 998-1007.
202. Fargnoli, M.C.; Spica, T.; Sera, F.; Pellacani, G.; Chiarugi, A.; Seidenari, S.; Carli, P.; Chimenti, S.; Peris, K. Re: MC1R, ASIP, and DNA repair in sporadic and familial melanoma in a Mediterranean population. J. Natl. Cancer Inst. 2006, 98, 144-145.
203. Wong, S.S.; Ainger, S.A.; Leonard, J.H.; Sturm, R.A. MC1R variant allele effects on UVR-induced phosphorylation of p38, p53, and DDB2 repair protein responses in melanocytic cells in culture. J. Invest. Dermatol. 2012, 132, 1452-1461.
204. Slominski, A.; Plonka, P.M.; Pisarchik, A.; Smart, J.L.; Tolle, V.; Wortsman, J.; Low, M.J. Preservation of eumelanin hair pigmentation in proopiomelanocortin-deficient mice on a nonagouti (a/a) genetic background. Endocrinology 2005, 146, 1245-1253.
205. Spry, M.L.; Vanover, J.C.; Scott, T.; Abona-Ama, O.; Wakamatsu, K.; Ito, S.; D'Orazio, J.A. Prolonged treatment of fair-skinned mice with topical forskolin causes persistent tanning and UV protection. Pigment. Cell Melanoma Res. 2009, 22, 219-229.
206. Khaled, M.; Levy, C.; Fisher, D.E. Control of melanocyte differentiation by a MITF-PDE4D3 homeostatic circuit. Genes Dev. 2010, 24, 2276-2281.
207. Ruwe, A.R.; Koikov, L.; Abdel-Malek, Z.; Haskell-Luevano, C.; Dirain, M.L.; Portillo, F.; Xiang, Z.; Wortman, M.; Knittel, J.J. Semi-rigid tripeptide agonists of melanocortin receptors. Bioorg. Med. Chem. Lett. 2009, 19, 5176-5181.