DNA Damage Caused by Laser Light Activated Hematoporphyrin Derivatives in Isolated Nuclei of Human Melanoma Cells

  • M. Artuc
  • M. Ramshad
  • C. Reinhold
  • H. Kappus
Part of the Archives of Toxicology book series (TOXICOLOGY, volume 12)


Hematoporphyrin derivatives (HPDs) are used in the chemotherapy of various tumors. They are a mixture of dimers and oligomers of hematoporphyrin linked by ether and ester bonds (for reviews see Kessel 1986a; Pottier and Truscott 1986). They accumulate in tumor cells and are cytotoxic after photosensitization with laser light. Reactive oxygen species formed during irradiation of HPDs are most likely responsible for the cytotoxicity observed (Keene et al. 1986; van Steveninck et al. 1986; Buettner and Hall 1987). However, the cellular target for these reactive oxygen species has not yet been identified. Critical oxidizable sites of mitochondria or the outer cellular membrane have been related to laser-activated HPD toxicity (Atlante et al. 1986; Kessel 1986b; Moan and Vistnes 1986; Salet 1986).


Reactive Oxygen Species Melanoma Cell Singlet Oxygen Human Malignant Melanoma Cell Line Hematoporphyrin Derivative 
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  1. Atlante A, Moreno G, Passarella S, Salet CH (1986) Hematoporphyrin derivative (photofrin II) photosensitization of isolated mitochondria: impairment of anion translocation. Biochem Biophys Res Commun 141:584–590PubMedCrossRefGoogle Scholar
  2. Blazek ER, Hariharan PV (1984) Alkaline elution studies of hematoporphyrin-derivative photosensitized DNA damage and repair in Chinese hamster ovary cells. Photochem Photobiol 40:5–13PubMedCrossRefGoogle Scholar
  3. Buettner GR, Hall RD (1987) Superoxide, hydrogen peroxide and singlet oxygen in hematoporphyrin derivative-cysteine, -NADH and -light systems. Biochim Biophys Acta 923:501–507PubMedCrossRefGoogle Scholar
  4. Dougherty TJ (1987) Photosensitizers: therapy and detection of malignant tumors. Photochem Photobiol 45:879–889PubMedCrossRefGoogle Scholar
  5. Gomer CJ, Smith DM (1980) Photoinactivation of Chinese hamster cells by hematoporphyrin derivative and red light. Photochem Photobiol 32:341–348PubMedCrossRefGoogle Scholar
  6. Halliwell B, Gutteridge JMC (1985) Free radicals in biology and medicine. Clarendon, OxfordGoogle Scholar
  7. Keene JP, Kessel D, Land EJ, Redmond RW, Truscott TG (1986) Direct detection of singlet oxygen sensitized by haematoporphyrin and related compounds. Photochem Photobiol 43:117–120PubMedCrossRefGoogle Scholar
  8. Kessel D (1986a) Review — photosensitization with derivatives of haematoporphyrin. Int J Radiat Biol 49:901–907CrossRefGoogle Scholar
  9. Kessel D (1986b) Sites of photosensitization by derivatives of hematoporphyrin. Photochem Photobiol 44:489–493PubMedCrossRefGoogle Scholar
  10. Mahmutoglu I, Kappus H (1985) Oxy radical formation during redox cycling of the bleomycin-iron (III) complex by NADPH-cytochrome P-450 reductase. Biochem Pharmacol 34:3091–3094PubMedCrossRefGoogle Scholar
  11. Mahmutoglu I, Kappus H (1987) Redox cycling of bleomycin-Fe (III) by an NADH-dependent enzyme, and DNA damage in isolated rat liver nuclei. Biochem Pharmacol 36:3677–3681PubMedCrossRefGoogle Scholar
  12. Moan J, Vistnes AI (1986) Porphyrin photosensitization of proteins in cell membranes as studied by spin-labelling and by quantification of DTNB-reactive SH-groups. Photochem Photobiol 44:15–19PubMedCrossRefGoogle Scholar
  13. Pottier R, Truscott TG (1986) The photochemistry of haematoporphyrin and related systems. Int J Radiat Biol 50:421–452CrossRefGoogle Scholar
  14. Salet Ch (1986) Hematoporphyrin and hematoporphyrin-derivative photosensitization of mitochondria. Biochimie 68:865–868PubMedCrossRefGoogle Scholar
  15. Schulte-Frohlinde D, von Sonntag C (1985) Radiolysis of DNA and model systems in the presence of oxygen. In: Sies H (ed) Oxidative stress. Academic, London, pp 11–40Google Scholar
  16. van Steveninck J, Tijssen K, Boegheim JPJ, van der Zee J, Dubbelman TMAR (1986) Pho-todynamic generation of hydroxyl radicals by hematoporphyrin derivative and light. Photochem Photobiol 44:711–716PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • M. Artuc
    • 1
  • M. Ramshad
    • 2
  • C. Reinhold
    • 1
  • H. Kappus
    • 1
  1. 1.Free University of BerlinBerlin 65Germany
  2. 2.Free University of BerlinBerlin 65Germany

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