Skip to main content

Advertisement

Log in

4-thiothymidine sensitization of DNA to UVA offers potential for a novel photochemotherapy

  • Perspective
  • Published:
Photochemical & Photobiological Sciences Aims and scope Submit manuscript

Abstract

Photochemotherapy, in which ultraviolet radiation (UVR: 280–400 nm) or visible light is combined with a photosensitizing drug to produce a therapeutic effect that neither drug or radiation can achieve alone, is a proven therapeutic strategy for a number of non-malignant hyperproliferative skin conditions and various cancers. Examples are psoralen plus UVA (320–400 nm) radiation (PUVA) and photodynamic therapy (PDT). All existing photochemotherapies have drawbacks–for example the association of PUVA with the development of skin cancer, and pain that is often associated with PDT treatment of skin lesions. There is a clear need to develop alternative approaches that involve lower radiation doses and/or improved selectivity for target cells. In this review, we explore the possibility to address this need by exploiting thionucleoside-mediated DNA photosensitisation to low, non toxic doses of UVA radiation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. R. S. Stern, E. J. Lunder, Risk of squamous cell carcinoma and methoxsalen (psoralen) and UV-A radiation (PUVA) - A meta-analysis, Arch. Dermatol., 1998, 134, 1582–1585.

    CAS  PubMed  Google Scholar 

  2. R. S. Stern, P. F. U. Study, The risk of melanoma in association with long-term exposure to PUVA, J. Am. Acad. Dermatol., 2001, 44, 755–761.

    CAS  PubMed  Google Scholar 

  3. R. S. Stern, Psoralen and ultraviolet a light therapy for psoriasis, N. Engl. J. Med., 2007, 357, 682–690.

    CAS  PubMed  Google Scholar 

  4. T. P. Singh, B. Huettner, H. Koefeler, G. Mayer, I. Bambach, K. Wallbrecht, M. P. Schon, P. Wolf, Platelet-Activating Factor Blockade Inhibits the T-Helper Type 17 Cell Pathway and Suppresses Psoriasis-Like Skin Disease in K5.hTGF-beta 1 Transgenic Mice, Am. J. Pathol., 2011, 178, 699–708.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. D. Papadopoulo, F. Sagliocco, D. Averbeck, Mutagenic Effects of 3-Carbethoxypsoralen and 8-Methoxypsoralen Plus 365-nm Irradiation in Mammalian-Cells, Mutat. Res., Genet. Toxicol., 1983, 124, 287–297.

    CAS  Google Scholar 

  6. A. R. Young, I. A. Magnus, A. C. Davies, N. P. Smith, A Comparison of the Phototumorigenic Potential of 8-MOP and 5-MOP in Hairless Albino Mice Exposed to Solar Simulated Radiation, Br. J. Dermatol., 1983, 108, 507–518.

    CAS  PubMed  Google Scholar 

  7. R. Knobler, M. L. Barr, D. R. Couriel, J. L. M. Ferrara, L. E. French, P. Jaksch, W. Reinisch, A. H. Rook, T. Schwarz, H. Greinix, Extracorporeal photopheresis: Past, present, and future, J. Am. Acad. Dermatol., 2009, 61, 652–665.

    PubMed  Google Scholar 

  8. P. Babilas, S. Schreml, M. Landthaler, R. M. Szeimies, Photodynamic therapy in dermatology: state-of-the-art, Photodermatol., Photoimmunol. Photomed., 2010, 26, 118–132.

    CAS  PubMed  Google Scholar 

  9. D. Fayter, M. Corbett, M. Heirs, D. Fox, A. Eastwood, A systematic review of photodynamic therapy in the treatment of pre-cancerous skin conditions, Barrett’s oesophagus and cancers of the biliary tract, brain, head and neck, lung, oesophagus and skin, Health Technol. Assess., 2010, 14, 1–288.

    CAS  PubMed  Google Scholar 

  10. J. H. Pinthus, A. Bogaards, R. Weersink, B. C. Wilson, J. Trachtenberg, Photodynamic therapy for urological malignancies: Past to current approaches, J. Urol., 2006, 175, 1201–1207.

    CAS  PubMed  Google Scholar 

  11. S. K. Attili, R. Dawe, S. Ibbotson, A review of pain experienced during topical photodynamic therapy–Our experience in Dundee, Photodiagn. Photodyn. Ther., 2011, 8, 53–57.

    Google Scholar 

  12. S. H. Ibbotson, Adverse effects of topical photodynamic therapy, Photodermatol., Photoimmunol. Photomed., 2011, 27, 116–130.

    PubMed  Google Scholar 

  13. A. M. Bugaj, Targeted photodynamic therapy - a promising strategy of tumor treatment, Photochem. Photobiol. Sci., 2011, 10, 1097–1109.

    CAS  PubMed  Google Scholar 

  14. M. Verhille, P. Couleaud, R. Vanderesse, D. Brault, M. Barberi-Heyob, C. Frochot, Modulation of Photosensitization Processes for an Improved Targeted Photodynamic Therapy, Curr. Med. Chem., 2010, 17, 3925–3943.

    CAS  PubMed  Google Scholar 

  15. A. R. Young, C. A. Chadwick, G. I. Harrison, O. Nikaido, J. Ramsden, C. S. Potten, The similarity of action spectra for thymine dimers in human epidermis and erythema suggests that DNA is the chromophore for erythema, J. Invest. Dermatol., 1998, 111, 982–988.

    CAS  PubMed  Google Scholar 

  16. A. Massey, Y.-Z. Xu, P. Karran, Photoactivation of DNA thiobases as a potential novel therapeutic option, Curr. Biol., 2001, 11, 1142–1146.

    CAS  PubMed  Google Scholar 

  17. A. Massey, Y. Z. Xu, P. Karran, Ambiguous coding is required for the lethal interaction between methylated DNA bases and DNA mismatch repair, DNA Repair, 2002, 1, 275–286.

    CAS  PubMed  Google Scholar 

  18. S. W. Pridgeon, R. Heer, G. A. Taylor, D. R. Newell, K. O’Toole, M. Robinson, Y. Z. Xu, P. Karran, A. V. Boddy, Thiothymidine combined with UVA as a potential novel therapy for bladder cancer, Br. J. Cancer, 2011, 104, 1869–1876.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. O. Reelfs, P. MacPherson, X. Ren, Y.-Z. Xu, P. Karran, A. Young, Identification of potentially cytotoxic lesions induced by UVA photoactivation of DNA 4-thiothymidine in human cells, Nucleic Acids Res., 2011 10.1093/nar/gkr674.

    Google Scholar 

  20. D. Cunningham, J. R. Zalcberg, U. Rath, I. Olver, E. Van Cutsem, C. Svensson, J. F. Seitz, P. Harper, D. Kerr, G. Perez-Manga et al., ‘Tomudex’ (ZD1694): results of a randomised trial in advanced colorectal cancer demonstrate efficacy and reduced mucositis and leucopenia. The ‘Tomudex’ Colorectal Cancer Study Group, Eur. J. Cancer, 1995, 31A, 1945–1954.

    CAS  PubMed  Google Scholar 

  21. P. F. Swann, T. R. Waters, D. C. Moulton, Y. Z. Xu, Q. Zheng, M. Edwards, R. Mace, Role of postreplicative DNA mismatch repair in the cytotoxic action of thioguanine, Science, 1996, 273, 1109–1111.

    CAS  PubMed  Google Scholar 

  22. O Reelfs, Y. Z. Xu, A. Massey, P. Karran, A. Storey, Thiothymidine plus low-dose UVA kills hyperproliferative human skin cells independently of their human papilloma virus status, Mol. Cancer Ther., 2007, 6, 2487–2495.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. J. L. Sherley, T. J. Kelly, Regulation of human thymidine kinase during the cell cycle, J. Biol. Chem., 1988, 263, 8350–8358.

    CAS  PubMed  Google Scholar 

  24. M. Hengstschlager, M. Pfeilstocker, E. Wawra, Thymidine kinase expression. A marker for malignant cells, Adv. Exp. Med. Biol., 1998, 431, 455–460.

    CAS  PubMed  Google Scholar 

  25. J. Cadet, T. Douki, J. L. Ravanat, P. Di Mascio, Sensitized formation of oxidatively generated damage to cellular DNA by UVA radiation, Photochem. Photobiol. Sci., 2009, 8, 903–911.

    CAS  PubMed  Google Scholar 

  26. P. O’Donovan, C. M. Perrett, X. Zhang, B. Montaner, Y. Z. Xu, C. A. Harwood, J. M. McGregor, S. L. Walker, F. Hanaoka, P. Karran, Azathioprine and UVA light generate mutagenic oxidative DNA damage, Science, 2005, 309, 1871–1874.

    PubMed  PubMed Central  Google Scholar 

  27. B. Montaner, P. O’Donovan, O. Reelfs, C. M. Perrett, X. Zhang, Y. Z. Xu, X. Ren, P. Macpherson, D. Frith, P. Karran, Reactive oxygen-mediated damage to a human DNA replication and repair protein, EMBO Rep., 2007, 8, 1074–1079.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. X. Zhang, G. Jeffs, X. Ren, P. O’Donovan, B. Montaner, C. M. Perrett, P. Karran, Y. Z. Xu, Novel DNA lesions generated by the interaction between therapeutic thiopurines and UVA light, DNA Repair, 2007, 6, 344–354.

    CAS  PubMed  Google Scholar 

  29. Y. Harada, T. Suzuki, T. Ichimura, Y. Z. Xu, Triplet formation of 4-thiothymidine and its photosensitization to oxygen studied by time-resolved thermal lensing technique, J. Phys. Chem. B, 2007, 111, 5518–5524.

    CAS  PubMed  Google Scholar 

  30. M. A. Warren, J. B. Murray, B. A. Connolly, Synthesis and characterisation of oligodeoxynucleotides containing thio analogues of (6-4) pyrimidine-pyrimidinone photo-dimers, J. Mol. Biol., 1998, 279, 89–100.

    CAS  PubMed  Google Scholar 

  31. C. Kielbassa, B. Epe, DNA damage induced by ultraviolet and visible light and its wavelength dependence, Methods Enzymol., 2000, 319, 436–445.

    CAS  PubMed  Google Scholar 

  32. 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 

  33. J. E. Cleaver, F. Cortes, L. H. Lutze, W. F. Morgan, A. N. Player, D. L. Mitchell, Unique DNA repair properties of a xeroderma pigmentosum revertant, Mol. Cell Biol., 1987, 7, 3353–3357.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. A. Favre, C. Saintome, J. L. Fourrey, P. Clivio, P. Laugaa, Thionucleobases as intrinsic photoaffinity probes of nucleic acid structure and nucleic acid-protein interactions, J. Photochem. Photobiol., B, 1998, 42, 109–124.

    CAS  PubMed  Google Scholar 

  35. R. O. Rahn, J. L. Hosszu, Photochemical Studies of Thymine in Ice, Photochem. Photobiol., 1969, 10, 131–137.

    CAS  PubMed  Google Scholar 

  36. P. Clivio, J. L. Fourrey, J. Gasche, A. Favre, DNA Photodamage Mechanistic Studies - Characterization of a Thietane Intermediate in a Model Reaction Relevant to 6-4 Lesions, J. Am. Chem. Soc., 1991, 113, 5481–5483.

    CAS  Google Scholar 

  37. P. Clivio, J. L. Fourrey, J. Gasche, A. Favre, Novel Insight into the Stereochemical Pathway Leading to (6-4) Pyrimidine-Pyrimidone Photoproducts in DNA, Tetrahedron Lett., 1992, 33, 1615–1618.

    CAS  Google Scholar 

  38. D. Perdiz, P. Grof, M. Mezzina, O. Nikaido, E. Moustacchi, E. Sage, Distribution and repair of bipyrimidine photoproducts in solar UV-irradiated mammalian cells. Possible role of Dewar photoproducts in solar mutagenesis, J. Biol. Chem., 2000, 275, 26732–26742.

    CAS  PubMed  Google Scholar 

  39. B. S. Rosenstein, D. L. Mitchell, The repair of DNA damages induced in normal human skin fibroblasts exposed to simulated sunlight, Radiat. Res., 1991, 126, 338–342.

    CAS  PubMed  Google Scholar 

  40. S. Courdavault, C. Baudouin, M. Charveron, B. Canguilhem, A. Favier, J. Cadet, T. Douki, Repair of the three main types of bipyrimidine DNA photoproducts in human keratinocytes exposed to UVB and UVA radiations, DNA Repair, 2005, 4, 836–844.

    CAS  PubMed  Google Scholar 

  41. B. Bartholomew, B. R. Braun, G. A. Kassavetis, E. P. Geiduschek, Probing close DNA contacts of RNA polymerase III transcription complexes with the photoactive nucleoside 4-thiodeoxythymidine, J. Biol. Chem., 1994, 269, 18090–18095.

    CAS  PubMed  Google Scholar 

  42. T. T. Nikiforov, B. A. Connolly, Oligodeoxynucleotides containing 4-thiothymidine and 6-thiodeoxyguanosine as affinity labels for the Eco RV restriction endonuclease and modification methylase, Nucleic Acids Res., 1992, 20, 1209–1214.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. J. T. Reardon, A. Sancar, Repair of DNA-polypeptide crosslinks by human excision nuclease, Proc. Natl. Acad. Sci. U. S. A., 2006, 103, 4056–4061.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. T. Nakano, A. Katafuchi, M. Matsubara, H. Terato, T. Tsuboi, T. Masuda, T. Tatsumoto, S. P. Pack, K. Makino, D. L. Croteau, B. Van Houten, K. Iijima, H. Tauchi, H. Ide, Homologous recombination but not nucleotide excision repair plays a pivotal role in tolerance of DNA-protein cross-links in mammalian cells, J. Biol. Chem., 2009, 284, 27065–27076.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. A. Ito, F. T. Robb, J. G. Peak, M. J. Peak, Base-specific damage induced by 4-thiouridine photosensitization with 334-nm radiation in M13 phage DNA, Photochem. Photobiol., 1988, 47, 231–240.

    CAS  PubMed  Google Scholar 

  46. M. C. Wei, T. Lindsten, V. K. Mootha, S. Weiler, A. Gross, M. Ashiya, C. B. Thompson, S. J. Korsmeyer, tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c, Genes Dev., 2000, 14, 2060–2071.

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  48. A. Ziegler, D. J. Leffell, S. Kunala, H. W. Sharma, M. Gailani, J. A. Simon, A. J. Halperin, H. P. Baden, P. E. Shapiro, A. E. Bale et al., Mutation hotspots due to sunlight in the p53 gene of nonmelanoma skin cancers, Proc. Natl. Acad. Sci. U. S. A., 1993, 90, 4216–4220.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. E. Sage, E. A. Drobetsky, E. Moustacchi, 8-Methoxypsoralen induced mutations are highly targeted at crosslinkable sites of photoaddition on the non-transcribed strand of a mammalian chromosomal gene, EMBO J., 1993, 12, 397–402.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. A. R. Young, I. A. Magnus, An Action Spectrum for 8-MOP Induced Sunburn Cells in Mammalian Epidermis, Br. J. Dermatol., 1981, 104, 541–548.

    CAS  PubMed  Google Scholar 

  51. K. H. Kaidbey, An Action Spectrum for 8-Methoxypsoralen-Sensitized Inhibition of DNA-Synthesis In vivo, J. Invest. Dermatol., 1985, 85, 98–101.

    CAS  PubMed  Google Scholar 

  52. R. M. Sayre, J. C. Dowdy, R. W. Gottschalk, Comparative effectiveness of clinically used light sources for cutaneous protoporphyrin IX-based photodynamic therapy, J. Cosmetic Laser Ther., 2011, 13, 63–68.

    Google Scholar 

  53. N. R. Attard, P. Karran, UVA photosensitization of thiopurines and skin cancer in organ transplant recipients, Photochem. Photobiol. Sci., 2012 10.1039/C1PP05194F.

    Google Scholar 

  54. A. Tewari, C. Lahmann, R. Sarkany, J. Bergemann, A. R. Young, Human erythema and matrix metalloproteinase-1 mRNA induction, in vivo, share an action spectrum which suggests common chromophores, Photochem. Photobiol. Sci., 2012 10.1039/C1PP05243H.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Olivier Reelfs.

Additional information

Contribution to the themed issue on the biology of UVA.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reelfs, O., Karran, P. & Young, A.R. 4-thiothymidine sensitization of DNA to UVA offers potential for a novel photochemotherapy. Photochem Photobiol Sci 11, 148–154 (2012). https://doi.org/10.1039/c1pp05188a

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1039/c1pp05188a

Navigation