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

被引:27
作者
Duez, P [1 ]
Hanocq, M [1 ]
Dubois, J [1 ]
机构
[1] Free Univ Brussels, Inst Pharm, Serv Chim Bioanalyt Toxicol & Chim Phys Appl, B-1050 Brussels, Belgium
关键词
D O I
10.1093/carcin/22.5.771
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 -amino-levulinic 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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收藏
页码:771 / 778
页数:8
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