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Cellular aspects of photocarcinogenesis

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Abstract

Many aspects are involved in photocarcinogenesis. Historically, genetic change caused by UV-B-induced pyrimidine photoproducts have been paid much attention. Indeed they are very important factors. However, recent reports indicate the involvement of many other factors. First, UV-B induces not only pyrimidine photoproducts but also DNA lesions modified by reactive oxygen species (ROS). Several reports pointed out that types of mutations that are not theoretically caused by pyrimidine photoproducts are frequently observed in the human skin cancers of sun-exposed areas and UV-B-induced murine skin cancers. In addition to transition-type mutations at dipyrimidine sites, mutations which may be induced by the presence of oxidative DNA damage, are frequently observed in the ras oncogene and p53 tumor suppressor gene in human skin cancers of sun-exposed area and in UV-induced mouse skin cancers. Second, recent studies have shown that not only UV-B but also UV-A is involved in photocarcinogenesis based on animal experiments whereas UV-B has been considered mostly responsible. UV-A induces indirect DNA damage via ROS and lipid peroxidation. ROS have been associated not only with initiation, but promotion and progression in the multistage carcinogenesis model. Third, biological responses other than direct influence by UV such as inflammatory and immunological responses and oxidative modifications of DNA and proteins appears also responsible for carcinogenesis. Persistent oxidative stress in cancer may also cause activation of transcription factors and protooncogenes such as c-fos and c-jun as well as genetic instability. Such a stress may also contribute to maintain their malignant characteristics. An integrated model for photocarcinogenesis is proposed.

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References

  1. B. K. Armstrong, A. Kricker, The epidemiology of UV induced skin cancer, J. Photochem. Photobiol., B, 2001, 63, 8–18.

    Article  CAS  Google Scholar 

  2. S. Hu, F. Ma, F. Collado-Mesa, R. S. Kirsner, UV radiation, latitude, and melanoma in US Hispanics and blacks, Arch. Dermatol. Res., 2004, 140, 819–824.

    Google Scholar 

  3. M. Das, D. Bickers, R. Santella R, H. Mukhtar, Altered patterns of cutaneous xenobiotic metabolism in UVB-induced squamous cell carcinoma in SKH-1 hairless mice, J. Invest. Dermatol., 1985, 84, 532–536.

    Article  CAS  PubMed  Google Scholar 

  4. C. Nishigori, M. Tanaka, S. Moriwaki, S. Imamura, H. Takebe, H, Accelerated appearance of skin tumors in hairless mice by repeated UV irradiation with initial intense exposure and characterization of the tumors, Jpn. J. Cancer Res., 1992, 83, 1172–1178.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. C. Nishigori, S. Moriwaki, H. Takebe, T. Tanaka, S. Imamura, Gene alterations and clinical characteristics of xeroderma pigmentosum group A patients in Japan, Arch. Dermatol. Res., 1994, 130, 191–197.

    Article  CAS  Google Scholar 

  6. A. Ziegler, A. S. Jonason, D. J. Leffell, J. A. Simon, H. W. Sharma, J. Kimmelman, L. Remington, T. Jacks, D. E. Brash, Sunburn and p53 in the onset of skin cancer, Nature, 1994, 372, 773–776.

    Article  CAS  PubMed  Google Scholar 

  7. F. de Gruijl, Action spectrum for photocarcinogenesis, Recent Results Cancer Res., 1995, 139, 21–30.

    Article  PubMed  Google Scholar 

  8. M. J. Ellison, J. D. Childs, Pyrimidine dimmers induced in escherichia coli DNA by ultraviolet radiation present in sunlight, Photochem. Photobiol., 1981, 34, 465–469.

    Article  CAS  PubMed  Google Scholar 

  9. J. Miller, Mutagenic specificity of ultraviolet light, J. Mol. Biol., 1985, 182, 45–65.

    Article  CAS  PubMed  Google Scholar 

  10. D. Brash, J. Rudolph, J. Simon, A. Lin, G. McKenna, H. Baden, A. Halperin, J. Ponte, A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma, Proc. Natl. Acad. Sci. USA, 1991, 88, 10124–10128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. W. Pierceall, L. Goldberg, M. Tainsky, T. Mukhopadhyay, H. Ananthaswamy, Ras gene mutation and amplification in human nonmelanoma skin cancers, Mol. Carcinog., 1991, 4, 196–202.

    Article  CAS  PubMed  Google Scholar 

  12. J. van der Schroeff, L. Evers, A. Boot, J. Bos, Ras oncogene mutations in basal cell carcinomas and squamous cell carcinomas of human skin, J. Invest. Dermatol., 1990, 94, 423–425.

    Article  PubMed  Google Scholar 

  13. C. Nishigori, S. Wang, J. Miyakoshi, M. Sato, T. Tsukada, T. Yagi, S. Imamura, H. Takebe, Mutations in ras genes in cells cultured from mouse skin tumors induced by ultraviolet irradiation, Proc. Natl. Acad. Sci. USA, 1994, 91, 7189–7193.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. N. Dumaz, C. Drougard, A. Sarasin, L. Daya-Grosjean, Specific UV-induced mutation spectrum in the p53 gene of skin tumors from DNA-repair-deficient xeroderma pigmentosum patients, Proc. Natl. Acad. Sci. USA, 1993, 90, 10529–10533.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. M. Sato, C. Nishigori, M. Zghal, T. Yagi, H. Takebe, Ultraviolet-specific mutations in p53 gene in skin tumors in xeroderma pigmentosum patients, Cancer Res., 1993, 53, 2944–2946.

    CAS  PubMed  Google Scholar 

  16. A. Spatz, G. Giglia-Mari, S. Benhamou, A. Sarasin, Association between DNA repair-deficiency and high level of p53 mutations in melanoma of Xeroderma pigmentosum, Cancer Res., 2001, 61, 2480–2486.

    CAS  PubMed  Google Scholar 

  17. G. Giglia-Mari, A. Sarasin, TP53 mutations in human skin cancers, Hum. Mutat., 2003, 21, 217–228.

    Article  CAS  PubMed  Google Scholar 

  18. L. Daya-Grosjean, N. Dumaz, A. Sarasin, The specificity of p53 mutation spectra in sunlight induced human cancers, J. Photochem. Photobiol., B, 1995, 28, 115–124.

    Article  CAS  Google Scholar 

  19. Y. Matsumura, M. Sato, C. Nishigori, Z. M. Zghal, T. Yagi, S. Imamura, H. Takebe, High prevalence of mutations in the p53 gene in poorly differentiated squamous cell carcinomas in xeroderma pigmentosum patients, J. Invest. Dermatol., 1995, 105, 399–401.

    Article  CAS  PubMed  Google Scholar 

  20. M. Sato, C. Nishigori, M. Zghal, T. Yagi, H. Takebe, Far less frequent mutaions in RAS genes than in the p53 gene in skin tumors of xeroderma pigmentosum patients, Mol. Carcinogenesis, 1994, 11, 98–105.

    Article  CAS  Google Scholar 

  21. Y. Matsumura, C. Nishigori, T. Yagi, S. Imamura, H. Takebe, Characterization of p53 gene mutations in basal cell carcinomas: comparison between sun-exposed areas and less-exposed skin areas, Int. J. Cancer, 1996, 65, 778–780.

    Article  CAS  PubMed  Google Scholar 

  22. J. van der Lubbe, H. Rosdorff, J. Bos, A. Van der Eb, Activation of N-ras induced by ultraviolet irradiation in vitro, Oncogene Res., 1988, 3, 9–20.

    PubMed  Google Scholar 

  23. H. Kasai, M. H. Chung, D. S. Jones, H. Inoue, H. Ishikawa, H. Kamiya, E. Ohtsuka, S. Nishimura, 8-Hydroxyguanine, a DNA adduct formed by oxygen radicals: its implication on oxygen radical-involved mutagenesis/carcinogenesis, J. Toxicol. Sci., 1991, 16, 95–105.

    Article  CAS  PubMed  Google Scholar 

  24. N. Basset-Seguin, J. Moles, V. Mils, O. Dereure, J. Guilhou, TP53 tumor suppressor gene and skin carcinogenesis, J. Invest. Dermatol., 1994, 103, 102S–106S.

    Article  CAS  PubMed  Google Scholar 

  25. K. Ito, S. Inoue, K. Yamamoto, S. Kawanishi, 8-Hydroxydeoxyguanosine formation at the 5℉ site of 5℉-GG-3℉ sequences in double-stranded DNA by UV radiation with riboflavin, J. Biol. Chem., 1993, 268, 13221–13227.

    Article  CAS  PubMed  Google Scholar 

  26. K. Kino, and H, Sugiyama, Possible cause of G-C → C-G transversion mutation by guanine oxidation product, imidazolone, Chem. Biol., 2001, 8, 369–378.

    Article  CAS  PubMed  Google Scholar 

  27. T. M. Reid, L. A. Loeb, Tandem double CC to TT mutations are produced by reactive oxygen species, Proc. Natl. Acad. Sci. USA, 1993, 90, 3904–3907.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Y. Hattori-Nakakuki, C. Nishigori, K. Okamoto, S. Imamura, H. Hiai, S. Toyokuni, Formation of 8-hydroxy-2℉-deoxyguanosine in epidermis of hairless mice exposed to near-UV, Biochem. Biophys. Res. Commun., 1994, 201, 1132–1139.

    Article  CAS  PubMed  Google Scholar 

  29. C. Nishigori, Y. Hattori, Y. Arima, Y. Miyachi, Photoageing and oxidative stress, Exp. Dermatol., 2003, 12, 18–21.

    Article  CAS  PubMed  Google Scholar 

  30. Y. Hattori, C. Nishigori, T. Tanaka, K. Uchida, O. Nikaido, T. Osawa, H. Hiai, S. Imamura, S. Toyokuni, 8-Hydroxy-2℉-deoxyguanosine is increased in epidermal cells of hairless mice after chronic UVB exposure, J. Invest. Dermatol., 1996, 107, 733–737.

    Article  CAS  PubMed  Google Scholar 

  31. J. Beckman, W. Koppenol, Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly, Am. J. Physiol., 1996, 271, C1424–1437.

    Article  CAS  PubMed  Google Scholar 

  32. U. Giri, S. Sharma, M. Abdulla, M. Athar, Evidence that in situ generated reactive oxygen species act as a potent stage I tumor promoter in mouse skin, Biochem. Biophys. Res. Commun., 1995, 209, 698–705.

    Article  CAS  PubMed  Google Scholar 

  33. R. Moore, D. Owens, G. Stamp, C. Arnott, F. Burke, N. East, H. Holdsworth, L. Turner, B. Rollins, M. Pasparakis, G. Kollias, F. Balkwill, Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis, Nat. Med., 1999, 5, 828–831.

    Article  CAS  PubMed  Google Scholar 

  34. F. Noonan, J. Recio, H. Takayama, P. Duray, M. Anver, W. Rush, E. de Fabo, G. Merlino, Neonatal sunburn and melanoma in mice, Nature, 2001, 413, 271–272.

    Article  CAS  PubMed  Google Scholar 

  35. P. Autier, J. Dore, Influence of sun exposures during childhood and during adulthood on melanoma risk. EPIMEL and EORTC Melanoma Cooperative Group. European Organisation for Research and Treatment of Cancer, Int. J. Cancer, 1998, 77, 533–537.

    Article  CAS  PubMed  Google Scholar 

  36. D. Whiteman, C. Whiteman, A. Green, Childhood sun exposure as a risk factor for melanoma: a systematic review of epidemiologic studies, Cancer Causes Control, 2001, 12, 69–82.

    Article  CAS  PubMed  Google Scholar 

  37. M. Kunisada, K. Sakumi, Y. Tominaga, A. Budiyanto, M. Ueda, M. Ichihashi, Y. Nakabeppu, C. Nishigori, 8-Oxoguanine Formation Induced by Chronic Ultraviolet B Exposure Makes Ogg1 Knockout Mice Susceptible to Skin Carcinogenesis, Cancer Res., 2005, 65, 6006–6010.

    Article  CAS  PubMed  Google Scholar 

  38. S. Toyokuni, K. Okamoto, J. Yodoi, H. Hiai, Persistent oxidative stress in cancer, FEBS. Lett., 1995, 358, 1–3.

    Article  CAS  PubMed  Google Scholar 

  39. D. Crawford, I. Zbinden, P. Amstad, P. Cerutti, Oxidant stress induces the proto-oncogenes c-fos and c-myc in mouse epidermal cells, Oncogene, 1988, 3, 27–32.

    CAS  Google Scholar 

  40. T. Douki, A. Reynaud-Angelin, J. Cadet, E. Sage, Bipyrimidine photoproducts rather than oxidative lesions are the main type of DNA damage involved in the genotoxic effect of solar UVA radiation, Biochemistry, 2003, 43, 9221–9226.

    Article  CAS  Google Scholar 

  41. S. Courdavault, C. Baudouin, M. Charveron, A. Favier, J. Cadet, T. Douki, Larger yield of cyclobutane dimers than 8-oxo-7,8-dihydroguanine in the DNA of UVA-irradiated human skin cells, Mutat. Res., 2004, 556, 1-2, Nov. 22, 135–142.

    Article  CAS  PubMed  Google Scholar 

  42. A. Besaratinia, T. W. Synold, B. Xi, G. P. Pfeifer, G-to-T transversions and small tandem base deletions are the hallmark of mutations induced by ultraviolet A radiation in mammalian cells, Biochemistry, 2004, 43, 8169–8177.

    Article  CAS  PubMed  Google Scholar 

  43. E. Kvam, R. Tyrrell, Induction of oxidative DNA base damage in human skin cells by UV and near visible radiation, Carcinogenesis, 1997, 18, 2379–2384.

    Article  CAS  PubMed  Google Scholar 

  44. J. Rosen, A. Prahalad, G. Schluter, D. Chen, G. Williams, Quinolone antibiotic photodynamic production of 8-oxo-7, 8-dihydro-2℉-deoxyguanosine in cultured liver epithelial cells, Photochem. Photobiol., 1997, 65, 990–996.

    Article  CAS  PubMed  Google Scholar 

  45. R. Phillipson, S. Tobi, J. Morris, T. McMillan, UV-A induces persistent genomic instability in human keratinocytes through an oxidative stress mechanism, Free Radical Biol. Med., 2002, 32, 474–480.

    Article  CAS  Google Scholar 

  46. E. Drobetsky, J. Turcotte, A. Chateauneuf, A role for ultraviolet A in solar mutagenesis, Proc. Natl. Acad. Sci. USA, 1995, 92, 2350–2354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. H. van Kranen, A. de Laat, J. van de Ven, P. Wester, A. de Vries, R. Berg, C. van Kreijl, F. de Gruijl, Low incidence of p53 mutations in UVA (365-nm)-induced skin tumors in hairless mice, Cancer Res., 1997, 57, 1238–1240.

    PubMed  Google Scholar 

  48. N. S. Agar, G. M. Halliday, R. S. Barnetson, H. N. Ananthaswamy, M. Wheeler, A. M. Jones, 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. R. Strange, A. Fryer, The glutathione S-transferases: influence of polymorphism on cancer susceptibility, IARC. Sci. Publ., 1999, 148, 231–249.

    CAS  Google Scholar 

  50. R. Setlow, E. Grist, K. Thompson, A. Woodhead, Wavelengths effective in induction of malignant melanoma, Proc. Natl. Acad. Sci. USA, 1993, 90, 6666–6670.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. H. Hill, G. Hill, UVA, pheomelanin and the carcinogenesis of melanoma, Pigm. Cell Res., 2000, 13, Suppl 8, 140–144.

    Article  Google Scholar 

  52. M. L. Kripke, Antigenicity of murine skin tumors induced by ultraviolet light, J. Natl. Cancer Inst., 1974, 53, 1333–1336.

    Article  CAS  PubMed  Google Scholar 

  53. M. T. Glover, C. M. Prober, I. M. Leigh, Skin cancer in renal transplant patients, Cancer Bull., 1993, 45, 220–224.

    Google Scholar 

  54. T. A. Lugar and T. S. Schwarz, in Skin Immune System, CRC Press, Boca Raton, FL, 1989.

    Google Scholar 

  55. J. M. Rivas, S. E. Ullrich, The role of IL-4, IL-10, and TNF-a in the immune suppression induced by ultraviolet radiation, J. Leukocyte Biol., 1994, 56, 769–775.

    Article  CAS  PubMed  Google Scholar 

  56. C. Nishigori, D. B. Yarosh, S. E. Ullrich, A. A. Vink, C. D. Bucana, L. Roza, M. L. Kripke, DNA damage triggers IL-10 cytokine production in UV-irradiated keratinocytes, Proc. Natl. Acad. Sci. USA, 1996, 93, 10354–10359.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. V. Shreedhar, T. Giese, V. W. Sung, S. E. Ullrich, A cytokine cascade including prostaglandin E2, IL-4, and IL-10 is responsible for UV-induced systemic immune suppression, J. Immunol., 1998, 160, 3783–3789.

    CAS  PubMed  Google Scholar 

  58. G. M. Halliday, Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis, Mutat. Res., 2005, 571, 107–120.

    Article  CAS  PubMed  Google Scholar 

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  1. Division of Dermatology, Department of Clinical Molecular Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Chikako Nishigori

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Nishigori, C. Cellular aspects of photocarcinogenesis. Photochem Photobiol Sci 5, 208–214 (2006). https://doi.org/10.1039/b507471a

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