Lasers in Medical Science

, Volume 1, Issue 1, pp 5–12 | Cite as

Porphyrin-sensitized photodynamic inactivation of cells: A review

  • Johan Moan


When mammalian cells are exposed to light in the presence of photosensitizers, such as porphyrins, a number of reactions takes place. The most important photoproduct is singlet oxygen, which reacts with and degrades a variety of biomolecules. This species can travel only about 0.1μm in a cell during its lifetime. Therefore, the structures most exposed to photodamage are those containing high concentrations of sensitizer. For porphyrins, membranes and mitochondria are such structures. Photosensitized damage to mitochondria and membranes has been observed by several techniques. The incubation time with sensitizers is critical since the rates of accumulation of sensitizer are different at different cellular locations. Several other aspects of the action of photosensitizers are reviewed: Have sublethal doses any effect on proliferation and DNA? How can photodynamic treatment act selectively on tumour tissue? Should photodynamic cancer treatment be combined with other therapies? Does photodynamic therapy work under low oxygen concentrations?

Key words

Photosensitization Porphyrins Cancer therapy Membrane damage 


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  1. 1.
    Policard A. Étude sur les aspects offerts par des tumeurs expérimentales examinée à la lumière de Wood.C R Soc Biol 1924,91:1423–4Google Scholar
  2. 2.
    Auler H, Banzer G. Untersuchungen über die Rolle der Porphyrine bei geschwulstkranken Menschen und Tieren.Z Krebsforsch 1943,53:65–8Google Scholar
  3. 3.
    Lipson RB, Baldes EJ, Olsen AM. The use of a derivative of hematoporphyrin in tumour detection.J Natl Cancer Inst 1961,26:1–11PubMedGoogle Scholar
  4. 4.
    Dougherty TJ, Potter WR, Weishaupt KR. The structure of the active component of hematoporphyrin derivative. In: Andreoni A, Cubeddu R (eds)Porphyrins in tumor phototherapy. New York: Plenum Press, 1984:23–35Google Scholar
  5. 5.
    Winkelman J, Slater G, Grossman J. The concentration in tumor and other tissues of parenterally administered tritium- and14C-labeled tetraporphyrine-sulfonate.Cancer Res 1967,27:2060–4PubMedGoogle Scholar
  6. 6.
    Jesionek A, von Tappeiner H. Zur Behandlung der Hautcarcinome mit fluorescierenden Stoffen.Dtsch Arch Klin Med 1905,82:223–7Google Scholar
  7. 7.
    Diamond I, Granelli SG, McDonagh AF et al. Photodynamic therapy of malignant tumours.Lancet 1972, ii:1175–7Google Scholar
  8. 8.
    Dougherty TJ. Activated dyes as antitumor agents.J Natl Cancer Inst 1974,52:1333–6PubMedGoogle Scholar
  9. 9.
    Moan J, Pettersen EO, Christensen T. The mechanism of photodynamic inactivation of human cells in vitro in the presence of haematoporphyrin.Br J Cancer 1979,39:398–407PubMedGoogle Scholar
  10. 10.
    Kosaki F, Saka T. Studies on the affinities of cells and their formative elements for porphyrin bodies.Mie Med J 1956,1:55–64Google Scholar
  11. 11.
    Moan J, Johannessen JV, Christensen T et al. Porphyrin-sensitized photoinactivation of human cells in vitro.Am J Pathol 1982,109:184–92PubMedGoogle Scholar
  12. 12.
    Malik Z, Djaldetti M. Destruction of erythroleukemia, myelocytic leukemia and Burkitt lymphoma cells by photoactivated protoporphyrin.Int J Cancer 1980,26:495–500PubMedGoogle Scholar
  13. 13.
    Dubbelman T, Leenhouts K, van Steveninck J. Photodynamic inactivation of L929 cells after treatment with hematoporphyrin derivative. In: Andreoni A, Cubeddy R (eds)Porphyrins in tumor phototherapy. New York: Plenum, 1984:167–75Google Scholar
  14. 14.
    Moan J, McGhie JB, Jacobsen PB. Photodynamic effects on cells in vitro exposed to hematoporphyrin derivative and light.Photochem Photobiol 1983,37:599–604PubMedGoogle Scholar
  15. 15.
    Girotti A, Deziel MR. Photodynamic action of protoporphyrin on resealed erythrocyte membranes: mechanisms of release of trapped markers. In: Kessel D, Dougherty TJ (eds)Porphyrin photosensitization. New York: Plenum, 1983:213–25Google Scholar
  16. 16.
    Van Steveninck J, Dubbelman T, Verweij H. Photo-dynamic membrane damage. In: Kessel D, Dougherty TJ (eds)Porphyrin photosensitization. New York: Plenum, 1983:226–40Google Scholar
  17. 17.
    Schothorst AA, DeHaas CAC, Suurmond D. Photo-chemical damage to skin fibroblasts caused by protoporphyrin and violet light.Arch Dermatol Res 1980,268:31–42CrossRefPubMedGoogle Scholar
  18. 18.
    Moan J. Porphyrin photosensitization of cells. In: Jori G, Perria C (eds)Photodynamic therapy of tumors and other diseases. Padova: Librero Publ, 1985: in pressGoogle Scholar
  19. 19.
    Moan J, Christensen T, Jacobsen PB. Porphyrin-sensitized photoinactivation of cells in vitro. In: Doiron DR, Gomer CF (eds)Porphyrin localization and treatment of tumors. New York: Alan R Liss, 1984:419–42Google Scholar
  20. 20.
    Moan J, Christensen T, Jacobsen PB. Photodynamic effects on cells in vitro labelled with hematoporphyrin derivative.Photobiochem Photobiophys 1984,7:349–58Google Scholar
  21. 21.
    Hilf R, Warne NW, Smail DB, Gibson SL. Photo-dynamic inactivation of selected intracellular enzymes by hematoporphyrin derivative and their relationship to tumor cell viability in vitro.Cancer Lett 1984,44:165–227Google Scholar
  22. 22.
    Hilf R, Smail DB, Murant RS et al. Hematoporphyrin derivative-induced photosensitivity of mitochondrial succinate dehydrogenase and selected cytosolic enzymes of R3230 AC mammary adenocarcinomas of rats.Cancer Res 1984,44:1483–8PubMedGoogle Scholar
  23. 23.
    Sandberg S, Romslo I. Porphyrin-induced photodamage at the cellular and the subcellular level as related to the solubility of the porphyrin.Clin Chim Acta 1981,109:193–201CrossRefPubMedGoogle Scholar
  24. 24.
    Sandberg S, Romslo I. Phototoxicity of uroporphyrin as related to its subcellular localization in rat livers after feeding with hexachlorobenzene.Photobiochem Photobiophys 1982,4:95–106Google Scholar
  25. 25.
    Christensen T. Multiplication of human NHIK 3025 cells exposed to porphyrins in combination with light.Br J Cancer 1981,44: 433–9PubMedGoogle Scholar
  26. 26.
    Moan J, Waksvik H, Christensen T. DNA single-strand breaks and sister chromatid exchanges induced by treatment with hematoporphyrin and light or by X-rays in human NHIK 3025 cells.Cancer Res 1980,40:2915–8PubMedGoogle Scholar
  27. 27.
    Gomer CJ, Rucker N, Banerjee A, Benedict WF. Comparison of mutagenicity and induction of sister chromatid exchange in Chinese hamster cells exposed to hematoporphyrin derivative, photoradiation, ionizing radiation, or UV radiation.Cancer Res 1983,43: 2622–7PubMedGoogle Scholar
  28. 28.
    Evensen JF, Moan J. Photodynamic action and chromosomal damage: a comparison of haematoporphyrin derivative (HPD) and light with X-irradiation.Br J Cancer 1982,45: 456–65PubMedGoogle Scholar
  29. 29.
    Christensen T, Feren K, Moan J, Pettersen E. Photo-dynamic effects of haematoporphyrin derivative on synchronous cells of different origin.Br J Cancer 1981,44:717–24PubMedGoogle Scholar
  30. 30.
    Moan J, Steen HB, Feren K, Christensen T. Uptake of hematoporphyrin derivative and sensitized photo-inactivation of C3H cells with different oncogenic potential.Cancer Lett 1981,14: 291–6CrossRefPubMedGoogle Scholar
  31. 31.
    Chang CT, Dougherty TJ. Photoradiation therapy: kinetics and thermodynamics of porphyrin uptake and loss in normal and malignant cells in culture.Radiat Res Soc 1978,74: 498–9Google Scholar
  32. 32.
    Henderson BW, Bellnier DA, Ziring B, Dougherty TJ. Aspects of the cellular uptake and retention of hematoporphyrin derivative and their correlation with the biological response to PRT in vivo.Adv Exp Med Biol 1983,160: 129–38PubMedGoogle Scholar
  33. 33.
    Mossman BT, Gray MJ, Silberman L, Lipson RL. Identification of neoplastic versus normal cells in human cervical cell culture.J Obstet Gynecol 1974,43: 635–9Google Scholar
  34. 34.
    Andreoni A, Cubeddu R, Silvestri SD, et al.Cancer Res 1983,43: 2076–80PubMedGoogle Scholar
  35. 35.
    Berns MW, Wilson M, Reutzepis P et al. Cell biology of hematoporphyrin derivative (HPD).Lasers Surg Med 1983,2: 261–6PubMedGoogle Scholar
  36. 36.
    Moan J, Smedshammer L, Christensen T. Photo-dynamic effects on human cells exposed to light in the presence of hematoporphyrin. pH effects.Cancer Lett 1980,9: 327–32CrossRefPubMedGoogle Scholar
  37. 37.
    Bugelski PJ, Porter CW, Dougherty TJ. Autoradiographic distribution of hematoporphyrin derivative in normal and tumor tissue of the mouse.Cancer Res 1981,41: 4606–12PubMedGoogle Scholar
  38. 38.
    Creekmore S, Zaharko DS. Modification of chemotherapeutic effects on L 12 10 cells using hematoporphyrin and light.Cancer Res 1983,43: 5252–7PubMedGoogle Scholar
  39. 39.
    Waldow SM, Dougherty TJ. Interaction of hyperthermia and photoradiation therapy.Radiat Res 1984,97: 380–5PubMedGoogle Scholar
  40. 40.
    Christensen T, Wahl A, Smedshammer L. Effects of haematoporphyrin derivative and light in combination with hyperthermia on cells in culture.Br J Cancer 1984,50: 85–9PubMedGoogle Scholar
  41. 41.
    Gomer CJ, Razum NJ. Acute skin response in albino mice following porphyrin photosensitization under oxic and anoxic conditions.Photochem Photobiol 1984,40: 435–9PubMedGoogle Scholar
  42. 42.
    Moan J, Sommer S. Oxygen dependence of the photo-sensitizing effect of hematoporphyrin derivative in NHIK 3025 cells.Cancer Res 1985,45:1608–9PubMedGoogle Scholar
  43. 43.
    Moan J, Sommer S. Action spectra for hematoporphyrin derivative and Photofrin II with respect to sensitization of human cells in vitro to photoinactivation.Photochem Photobiol 1984,40: 631–4PubMedGoogle Scholar
  44. 44.
    Rosseau J, Autenrieth D, van Lier JE. Synthesis, tissue distribution and tumor uptake of [99Tc] tetrasulfo-phthalocyanine.Int. J Appl Radiat Isot 1983,34: 571–9PubMedGoogle Scholar
  45. 45.
    Hisazumi H, Naito K, Misaki T et al. An experimental study of photodynamic therapy using a pulsed gold vapour laser. In: Jori G, Perria C (eds)Photodynamic therapy of tumors and other diseases. Padova: Librero Publ, 1985: in pressGoogle Scholar
  46. 46.
    Cowled PA, Grace JR, Forbes IJ. Comparison of the efficacy of pulsed and continuous-wave red laser light in induction of photo-cytotoxicity by haematoporphyrin derivative.Photochem Photobiol 1984,39:115–7PubMedGoogle Scholar

Copyright information

© Baillière Tindall 1986

Authors and Affiliations

  • Johan Moan
    • 1
  1. 1.Norsk Hydro's Institute for Cancer ResearchThe Norwegian Radium HospitalOslo 3Norway

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