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Carcinogenesis, Vol. 22, No. 5, 771-778, May 2001
© 2001 Oxford University Press

CARCINOGENESIS

Photodynamic DNA damage mediated by {delta}-aminolevulinic acid-induced porphyrins

P. Duez1,, M. Hanocq and J. Dubois

Institut de Pharmacie, Service de Chimie Bioanalytique, de Toxicologie et de Chimie Physique Appliquée, Université Libre de Bruxelles, CP 205/1, Bd du Triomphe, 1050 Bruxelles, Belgium

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 {delta}-aminolevulinic acid ({delta}-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 {delta}-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.


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