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DNA damage spectra induced by photosensitization

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Abstract

DNA damage induced by photosensitization is not only responsible for the genotoxic effects of various types of drugs in the presence of light, but is also relevant for some of the adverse effects of sunlight, in particular in the UVA and visible range of the spectrum. The types of DNA modifications induced are very diverse and include pyrimidine dimers, covalent adducts, various base modifications generated by oxidation, single-strand breaks and (regular and oxidized) sites of base loss. The ratios in which the various modifications are formed (damage spectra) can be regarded as a fingerprint of the damaging mechanism. Here, we describe the damage spectra of various classes of photosensitizers in relation to the underlying damaging mechanisms. In mammalian cells irradiated with solar radiation, damage at wavelengths <400 nm is characteristic for a (not yet identified) endogenous type-I or type-II photosensitizer. In the UVA range, however, both direct DNA excitation and photosensitized damage appear to be relevant, and there are indications that other chromophore(s) are involved than in the visible range.

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References

  1. S. Brendler-Schwaab, A. Czich, B. Epe, E. Gocke, B. Kaina, L. Muller, D. Pollet, D. Utesch, Photochemical genotoxicity: principles and test methods. Report of a GUM task force, Mutat. Res., 2004, 566, 65–91.

    CAS  PubMed  Google Scholar 

  2. J. Cadet, T. Douki, J. L. Ravanat, Measurement of oxidatively generated base damage in cellular DNA, Mutat. Res., 2011, 711, 3–12.

    CAS  PubMed  Google Scholar 

  3. J. Cadet, E. Sage, T. Douki, Ultraviolet radiation-mediated damage to cellular DNA, Mutat. Res., 2005, 571, 3–17.

    CAS  PubMed  Google Scholar 

  4. ESCODD, Measurement of DNA oxidation in human cells by chromatographic and enzymic methods, Free Radical Biol. Med., 2003, 34, 1089–1099.

    Google Scholar 

  5. W. L. Neeley, J. M. Essigmann, Mechanisms of formation, genotoxicity, and mutation of guanine oxidation products, Chem. Res. Toxicol., 2006, 19, 491–505.

    CAS  PubMed  Google Scholar 

  6. J. Musarrat, A. A. Wani, Quantitative immunoanalysis of promutagenic 8-hydroxy-2’-deoxyguanosine in oxidized DNA, Carcinogenesis, 1994, 15, 2037–2043.

    CAS  PubMed  Google Scholar 

  7. Y. Nakae, P. J. Stoward, I. A. Bespalov, R. J. Melamede, S. S. Wallace, A new technique for the quantitative assessment of 8-oxoguanine in nuclear DNA as a marker of oxidative stress. Application to dystrophin-deficient DMD skeletal muscles, Histochem. Cell Biol., 2005, 124, 335–345.

    CAS  PubMed  Google Scholar 

  8. B. Epe, J. Hegler, Oxidative DNA damage: endonuclease fingerprinting, Methods Enzymol., 1994, 234, 122–131.

    CAS  PubMed  Google Scholar 

  9. A. Hartwig, H. Dally, R. Schlepegrell, Sensitive analysis of oxidative DNA damage in mammalian cells: use of the bacterial Fpg protein in combination with alkaline unwinding, Toxicol. Lett., 1996, 88, 85–90.

    CAS  PubMed  Google Scholar 

  10. A. Azqueta, K. B. Gutzkow, G. Brunborg, A. R. Collins, Towards a more reliable comet assay: Optimising agarose concentration, unwinding time and electrophoresis conditions, Mutat. Res., 2011, 724, 41–45.

    CAS  PubMed  Google Scholar 

  11. A. R. Collins, The use of bacterial repair endonucleases in the comet assay, Methods Mol. Biol., 2011, 691, 137–147.

    CAS  PubMed  Google Scholar 

  12. D. Averbeck, M. Dardalhon, N. Magana-Schwencke, Repair of furocoumarin-plus-UVA-induced damage and mutagenic consequences in eukaryotic cells, J. Photochem. Photobiol., B, 1990, 6, 221–236.

    CAS  PubMed  Google Scholar 

  13. G. E. Pfyffer, B. U. Pfyffer, G. H. Towers, Monoaddition of dictamnine to synthetic double-stranded polydeoxyribonucleotides in UVA and the effect of photomodified DNA on template activity, Photochem. Photobiol., 1982, 35, 793–797.

    CAS  PubMed  Google Scholar 

  14. E. Sage, T. Le Doan, V. Boyer, D. E. Helland, L. Kittler, C. Helene, E. Moustacchi, Oxidative DNA damage photo-induced by 3-carbethoxypsoralen and other furocoumarins. Mechanisms of photo-oxidation and recognition by repair enzymes, J. Mol. Biol., 1989, 209, 297–314.

    CAS  PubMed  Google Scholar 

  15. F. Bosca, V. Lhiaubet-Vallet, M. C. Cuquerella, J. V. Castell, M. A. Miranda, The triplet energy of thymine in DNA, J. Am. Chem. Soc., 2006, 128, 6318–6319.

    CAS  PubMed  Google Scholar 

  16. A. Moysan, A. Viari, P. Vigny, L. Voituriez, J. Cadet, E. Moustacchi, E. Sage, Formation of cyclobutane thymine dimers photosensitized by pyridopsoralens: quantitative and qualitative distribution within DNA, Biochemistry, 1991, 30, 7080–7088.

    CAS  PubMed  Google Scholar 

  17. V. Lhiaubet-Vallet, M. C. Cuquerella, J. V. Castell, F. Bosca, M. A. Miranda, Triplet excited fluoroquinolones as mediators for thymine cyclobutane dimer formation in DNA, J. Phys. Chem. B, 2007, 111, 7409–7414.

    CAS  PubMed  Google Scholar 

  18. K. S. Robinson, N. J. Traynor, H. Moseley, J. Ferguson, J. A. Woods, Cyclobutane pyrimidine dimers are photosensitised by carprofen plus UVA in human HaCaT cells, Toxicol. In Vitro, 2010, 24, 1126–1132.

    CAS  PubMed  Google Scholar 

  19. D. Roca-Sanjuan, G. Olaso-Gonzalez, I. Gonzalez-Ramirez, L. Serrano-Andres, M. Merchan, Molecular basis of DNA photodimerization: intrinsic production of cyclobutane cytosine dimers, J. Am. Chem. Soc., 2008, 130, 10768–10779.

    CAS  PubMed  Google Scholar 

  20. S. Mouret, C. Philippe, J. Gracia-Chantegrel, A. Banyasz, S. Karpati, D. Markovitsi, T. Douki, UVA-induced cyclobutane pyrimidine dimers in DNA: a direct photochemical mechanism?, Org. Biomol. Chem., 2010, 8, 1706–1711.

    CAS  PubMed  Google Scholar 

  21. D. Markovitsi, T. Gustavsson, A. Banyasz, Absorption of UV radiation by DNA: spatial and temporal features, Mutat. Res., 2010, 704, 21–28.

    CAS  PubMed  Google Scholar 

  22. B. Epe, H. Henzl, W. Adam, C. R. Saha-Moller, Endonuclease-sensitive DNA modifications induced by acetone and acetophenone as photosensitizers, Nucleic Acids Res., 1993, 21, 863–869.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. W. Mu, Q. Han, Z. Luo, Y. Wang, Production of cis-syn thymine-thymine cyclobutane dimer oligonucleotide in the presence of acetone photosensitizer, Anal. Biochem., 2006, 353, 117–123.

    CAS  PubMed  Google Scholar 

  24. S. Steenken, S. V. Jovanovic, How easily oxidizable is DNA? One-electron reduction potentials of adenosine and guanosine radicals in aqueous solution, J. Am. Chem. Soc., 1997, 119, 617–618.

    CAS  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.

    CAS  PubMed  Google Scholar 

  26. I. Saito, M. Takayama, H. Sugiyama, K. Nakatani, Photoinduced DNA Cleavage Via Electron-Transfer - Demonstration That Guanine Residues Located 5’ to Guanine Are the Most Electron-Donating Sites, J. Am. Chem. Soc., 1995, 117, 6406–6407.

    CAS  Google Scholar 

  27. H. Sugiyama, I. Saito, Theoretical studies of GC-specific photocleavage of DNA via electron transfer: Significant lowering of ionization potential and 5’-localization of HOMO of stacked GG bases in B-form DNA, J. Am. Chem. Soc., 1996, 118, 7063–7068.

    CAS  Google Scholar 

  28. J. Cadet, T. Douki, J. L. Ravanat, Oxidatively generated damage to the guanine moiety of DNA: mechanistic aspects and formation in cells, Acc. Chem. Res., 2008, 41, 1075–1083.

    CAS  PubMed  Google Scholar 

  29. M. L. Wood, M. Dizdaroglu, E. Gajewski, J. M. Essigmann, Mechanistic studies of ionizing radiation and oxidative mutagenesis: genetic effects of a single 8-hydroxyguanine (7-hydro-8-oxoguanine) residue inserted at a unique site in a viral genome, Biochemistry, 1990, 29, 7024–7032.

    CAS  PubMed  Google Scholar 

  30. K. C. Cheng, D. S. Cahill, H. Kasai, S. Nishimura, L. A. Loeb, 8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G—T and A—C substitutions, J. Biol. Chem., 1992, 267, 166–172.

    CAS  PubMed  Google Scholar 

  31. M. Moriya, Single-stranded shuttle phagemid for mutagenesis studies in mammalian cells: 8-oxoguanine in DNA induces targeted G.C→T.A transversions in simian kidney cells, Proc. Natl. Acad. Sci. U. S. A., 1993, 90, 1122–1126.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. D. Ballmaier, B. Epe, Oxidative DNA damage induced by potassium bromate under cell-free conditions and in mammalian cells, Carcinogenesis, 1995, 16, 335–342.

    CAS  PubMed  Google Scholar 

  33. B. Matter, D. Malejka-Giganti, A. S. Csallany, N. Tretyakova, Quantitative analysis of the oxidative DNA lesion, 2,2-diamino-4-(2-deoxy-beta-D-erythro-pentofuranosyl)amino]-5(2H)-oxazolon e (oxazolone), in vitro and in vivo by isotope dilution-capillary HPLC-ESI-MS/MS, Nucleic Acids Res., 2006, 34, 5449–5460.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. M. Dizdaroglu, G. Kirkali, P. Jaruga, Formamidopyrimidines in DNA: mechanisms of formation, repair, and biological effects, Free Radical Biol. Med., 2008, 45, 1610–1621.

    CAS  Google Scholar 

  35. I. Schulz, H. C. Mahler, S. Boiteux, B. Epe, Oxidative DNA base damage induced by singlet oxygen and photosensitization: recognition by repair endonucleases and mutagenicity, Mutat. Res., 2000, 461, 145–156.

    CAS  PubMed  Google Scholar 

  36. K. Kino, I. Saito, H. Sugiyama, Product analysis of GG-specific photooxidation of DNA via electron transfer: 2-aminoimidazolone as a major guanine oxidation product, J. Am. Chem. Soc., 1998, 120, 7373–7374.

    CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  38. M. Hariharan, S. C. Karunakaran, D. Ramaiah, I. Schulz, B. Epe, Photoinduced DNA damage efficiency and cytotoxicity of novel viologen linked pyrene conjugates, Chem. Commun., 2010, 46, 2064–2066.

    CAS  Google Scholar 

  39. M. M. Gonzalez, M. Pellon-Maison, M. A. Ales-Gandolfo, M. R. Gonzalez-Baro, R. Erra-Balsells, F. M. Cabrerizo, Photosensitized cleavage of plasmidic DNA by norharmane, a naturally occurring beta-carboline, Org. Biomol. Chem., 2010, 8, 2543–2552.

    CAS  PubMed  Google Scholar 

  40. C. S. Foote, Definition of type I and type II photosensitized oxidation, Photochem. Photobiol., 1991, 54, 659.

    CAS  PubMed  Google Scholar 

  41. F. Bergeron, F. Auvre, J. P. Radicella, J. L. Ravanat, HO* radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases, Proc. Natl. Acad. Sci. U. S. A., 2010, 107, 5528–5533.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. J. Cadet, T. Douki, D. Gasparutto, J. L. Ravanat, Oxidative damage to DNA: formation, measurement and biochemical features, Mutat. Res., 2003, 531, 5–23.

    CAS  PubMed  Google Scholar 

  43. J. P. Pouget, S. Frelon, J. L. Ravanat, I. Testard, F. Odin, J. Cadet, Formation of modified DNA bases in cells exposed either to gamma radiation or to high-LET particles, Radiat. Res., 2002, 157, 589–595.

    CAS  PubMed  Google Scholar 

  44. K. W. Kohn, L. C. Erickson, R. A. Ewig, C. A. Friedman, Fractionation of DNA from mammalian cells by alkaline elution, Biochemistry, 1976, 15, 4629–4637.

    CAS  PubMed  Google Scholar 

  45. M. Häring, H. Rudiger, B. Demple, S. Boiteux, B. Epe, Recognition of oxidized abasic sites by repair endonucleases, Nucleic Acids Res., 1994, 22, 2010–2015.

    PubMed  PubMed Central  Google Scholar 

  46. B. Epe, D. Ballmaier, W. Adam, G. N. Grimm, C. R. Saha-Moller, Photolysis of N-hydroxpyridinethiones: a new source of hydroxyl radicals for the direct damage of cell-free and cellular DNA, Nucleic Acids Res., 1996, 24, 1625–1631.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. B. Epe, M. Haring, D. Ramaiah, H. Stopper, M. M. Abou-Elzahab, W. Adam, C. R. Saha-Moller, DNA damage induced by furocoumarin hydroperoxides plus UV (360 nm), Carcinogenesis, 1993, 14, 2271–2276.

    CAS  PubMed  Google Scholar 

  48. H. C. Mahler, I. Schulz, W. Adam, G. N. Grimm, C. R. Saha-Moller, B. Epe, tert-Butoxyl radicals generate mainly 7,8-dihydro-8-oxoguanine in DNA, Mutat. Res., 2001, 461, 289–299.

    CAS  PubMed  Google Scholar 

  49. Y. Ye, J. G. Muller, W. Luo, C. L Mayne, A. J. Shallop, R. A. Jones, C. J. Burrows, Formation of 13C-, 15N-, and 18O-labeled guanidinohydantoin from guanosine oxidation with singlet oxygen. Implications for structure and mechanism, J. Am. Chem. Soc., 2003, 125, 13926–13927.

    CAS  PubMed  Google Scholar 

  50. J. E. McCallum, C. Y. Kuniyoshi, C. S. Foote, Characterization of 5-hydroxy-8-oxo-7,8-dihydroguanosine in the photosensitized oxidation of 8-oxo-7,8-dihydroguanosine and its rearrangement to spiroiminodihydantoin, J. Am. Chem. Soc., 2004, 126, 16777–16782.

    CAS  PubMed  Google Scholar 

  51. J. L. Ravanat, P. Di Mascio, G. R. Martinez, M. H. Medeiros, J. Cadet, Singlet oxygen induces oxidation of cellular DNA, J. Biol. Chem., 2000, 275, 40601–40604.

    CAS  PubMed  Google Scholar 

  52. J. L. Ravanat, S. Sauvaigo, S. Caillat, G. R. Martinez, M. H. Medeiros, P. Di Mascio, A. Favier, J. Cadet, Singlet oxygen-mediated damage to cellular DNA determined by the comet assay associated with DNA repair enzymes, Biol. Chem., 2004, 385, 17–20.

    CAS  PubMed  Google Scholar 

  53. E. Muller, S. Boiteux, R. P. Cunningham, B. Epe, Enzymatic recognition of DNA modifications induced by singlet oxygen and photosensitizers, Nucleic Acids Res., 1990, 18, 5969–5973.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. O. Will, E. Gocke, I. Eckert, I. Schulz, M. Pflaum, H. C. Mahler, B. Epe, Oxidative DNA damage and mutations induced by a polar photosensitizer, Ro19-8022, Mutat Res., 1999, 435, 89–101.

    CAS  PubMed  Google Scholar 

  55. M. E. Serrentino, A. Catalfo, A. R. Angelin, G. de Guidi, E. Sage, Photosensitization induced by the antibacterial fluoroquinolone Rufloxacin leads to mutagenesis in yeast, Mutat Res., 2010, 692, 34–41.

    CAS  PubMed  Google Scholar 

  56. E. Gocke, Review of the genotoxic properties of chlorpromazine and related phenothiazines, Mutat Res., 1996, 366, 9–21.

    PubMed  Google Scholar 

  57. T. A. Ciulla, G. A. Epling, I. E. Kochevar, Photoaddition of chlorpromazine to guanosine-5’-monophosphate, Photochem. Photobiol., 1986, 43, 607–613.

    CAS  PubMed  Google Scholar 

  58. A. W. Girotti, Photosensitized oxidation of membrane lipids: reaction pathways, cytotoxic effects, and cytoprotective mechanisms, J. Photochem. Photobiol., B, 2001, 63, 103–113.

    CAS  PubMed  Google Scholar 

  59. L. J. Marnett, Oxyradicals and DNA damage, Carcinogenesis, 2000, 21, 361–370.

    CAS  PubMed  Google Scholar 

  60. H. Bartsch, J. Nair, Ultrasensitive and specific detection methods for exocylic DNA adducts: markers for lipid peroxidation and oxidative stress, Toxicology, 2000, 153, 105–114.

    CAS  PubMed  Google Scholar 

  61. I. G. Minko, I. D. Kozekov, T. M. Harris, C. J. Rizzo, R. S. Lloyd, M. P. Stone, Chemistry and biology of DNA containing 1,N(2)-deoxyguanosine adducts of the alpha,beta-unsaturated aldehydes acrolein, crotonaldehyde, and 4-hydroxynonenal, Chem. Res. Toxicol., 2009, 22, 759–778.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. G. P. Voulgaridou, I. Anestopoulos, R. Franco, M. I. Panayiotidis, A. Pappa, DNA damage induced by endogenous aldehydes: Current state of knowledge, Mutat. Res., 2011, 711, 13–27.

    CAS  PubMed  Google Scholar 

  63. C. Kielbassa, L. Roza, B. Epe, Wavelength dependence of oxidative DNA damage induced by UV and visible light, Carcinogenesis, 1997, 18, 811–816.

    CAS  PubMed  Google Scholar 

  64. J. P. Pouget, T. Douki, M. J. Richard, J. Cadet, DNA damage induced in cells by gamma and UVA radiation as measured by HPLC/GC-MS and HPLC-EC and Comet assay, Chem. Res. Toxicol., 2000, 13, 541–549.

    CAS  PubMed  Google Scholar 

  65. 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, 42, 9221–9226.

    CAS  PubMed  Google Scholar 

  66. 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, 135–142.

    CAS  PubMed  Google Scholar 

  67. M. Pflaum, C. Kielbassa, M. Garmyn, B. Epe, Oxidative DNA damage induced by visible light in mammalian cells: extent, inhibition by antioxidants and genotoxic effects, Mutat. Res., 1998, 408, 137–146.

    CAS  PubMed  Google Scholar 

  68. G. T. Wondrak, M. K. Jacobson, E. L. Jacobson, Endogenous UVA-photosensitizers: mediators of skin photodamage and novel targets for skin photoprotection, Photochem. Photobiol. Sci., 2006, 5, 215–237.

    CAS  PubMed  Google Scholar 

  69. B. Epe, Role of endogenous oxidative DNA damage in carcinogenesis: what can we learn from repair-deficient mice?, Biol. Chem., 2002, 383, 467–475.

    CAS  PubMed  Google Scholar 

  70. S. Hoffmann-Dörr, R. Greinert, B. Volkmer, B. Epe, Visible light (>395 nm) causes micronuclei formation in mammalian cells without generation of cyclobutane pyrimidine dimers, Mutat. Res., 2005, 572, 142–149.

    PubMed  Google Scholar 

  71. M. A. Bachelor, G. T. Bowden, UVA-mediated activation of signaling pathways involved in skin tumor promotion and progression, Semin. Cancer Biol., 2004, 14, 131–138.

    CAS  PubMed  Google Scholar 

  72. S. Boiteux, M. Guillet, Abasic sites in DNA: repair and biological consequences in Saccharomyces cerevisiae, DNA Repair, 2004, 3, 1–12.

    CAS  PubMed  Google Scholar 

  73. S. Bjelland, E. Seeberg, Mutagenicity, toxicity and repair of DNA base damage induced by oxidation, Mutat. Res., 2003, 531, 37–80.

    CAS  PubMed  Google Scholar 

  74. H. E. Krokan, R. Standal, G. Slupphaug, DNA glycosylases in the base excision repair of DNA, Biochem. J., 1997, 325(Pt 1) 1–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. M. Dizdaroglu, Base-excision repair of oxidative DNA damage by DNA glycosylases, Mutat. Res., 2005, 591, 45–59.

    CAS  PubMed  Google Scholar 

  76. W. Eiberger, B. Volkmer, R. Amouroux, C. Dherin, J. P. Radicella, B. Epe, Oxidative stress impairs the repair of oxidative DNA base modifications in human skin fibroblasts and melanoma cells, DNA Repair, 2008, 7, 912–921.

    CAS  PubMed  Google Scholar 

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Correspondence to Bernd Epe.

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Contribution to the themed issue on the biology of UVA.

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Epe, B. DNA damage spectra induced by photosensitization. Photochem Photobiol Sci 11, 98–106 (2012). https://doi.org/10.1039/c1pp05190c

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