Photodynamic DNA damage mediated by delta-aminolevulinic acid-induced porphyrins.
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.
Duez
P
P
Institut de Pharmacie, Service de Chimie Bioanalytique, de Toxicologie et de Chimie Physique Appliquée, Université Libre de Bruxelles, CP 205/1, Belgium. pduez@ulb.ac.be
Hanocq
M
M
Dubois
J
J
D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D004249:DNA Damage; D006801:Humans; D051379:Mice; D011524:Protoporphyrins / Q000096:biosynthesis / Q000737:chemistry / Q000633:toxicity*; D013050:Spectrometry, Fluorescence; D014407:Tumor Cells, Cultured
D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX