Journal Article

Photodynamic DNA damage mediated by δ-aminolevulinic acid-induced porphyrins

P. Duez, M. Hanocq and J. Dubois

in Carcinogenesis

Volume 22, issue 5, pages 771-778
Published in print May 2001 | ISSN: 0143-3334
Published online May 2001 | e-ISSN: 1460-2180 | DOI:
Photodynamic DNA damage mediated by δ-aminolevulinic acid-induced porphyrins

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The mutagenic properties of UVA are thought to be predominantly radical-mediated, which supposes endogenous sensitizers. In order to investigate a possible role of porphyrins, their synthesis was induced in a murine leukemia P388D1 cell model by treatment with δ-aminolevulinic acid (δ-ala). Intra-cellular protoporphyrin IX reached a plateau after about 2 h, whereas soluble porphyrins, probably the photostable uro- and/or coproporphyrins, were excreted. Irradiation of treated cells by UVA (tanning lamp) but also by visible light was found to generate in DNA a significant increase of 8-oxo-7,8-dihydro-2′-deoxyguanosine, a mutagenic marker of oxidative damage. The different parameters involved in this photodynamic effect are reported, namely δ-ala concentration and loading time, light dosage and the influence of intracellular and medium-excreted porphyrins. These results point to an implication of porphyrins in solar-induced carcinogenicity but also in possible adverse effects of the medical applications of photodynamic therapy and diagnosis.

Keywords: δ-ala, δ-aminolevulinic acid; dG, 2′-deoxyguanosine; G, guanosine; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PBS, phosphate buffered saline; PDD, photodynamic diagnosis; PDT, photodynamic therapy; PP IX, protoporphyrin IX; ROS, reactive oxygen species.

Journal Article.  6710 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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