Journal Article

High efficiency of 5-aminolevulinate-photodynamic treatment using UVA irradiation

Darius P. Buchczyk, Lars-Oliver Klotz, Kerstin Lang, Clemens Fritsch and Helmut Sies

in Carcinogenesis

Volume 22, issue 6, pages 879-883
Published in print June 2001 | ISSN: 0143-3334
Published online June 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.6.879
High efficiency of 5-aminolevulinate-photodynamic treatment using UVA irradiation

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Photodynamic therapy (PDT) is being used clinically for the treatment of skin cancers. One concept of delivering the employed photosensitizer directly to target cells is to stimulate cellular synthesis of sensitizers such as porphyrins. ALA (5-aminolevulinate) is applied as a precursor of porphyrins which then serve as endogenous photosensitizers. Upon irradiation, reactive oxygen species, predominantly singlet oxygen, are generated, leading to cell death. ALA–PDT using red light (550–750 nm) is known to lead to the activation of stress kinases, such as c-Jun-N-terminal kinase and p38. These kinases are also activated by UVA (320–400 nm), whose biological effects are mediated in part by singlet oxygen. In the present study, the efficiency of a combination of both treatment strategies, ALA–PDT and UVA, in cytotoxicity and activation of stress kinases was investigated taking human skin fibroblasts as a model. Compared with the commonly used ALA–PDT with red light (LD50 = 13.5 J/cm2), UVA–ALA–PDT was 40-fold more potent in killing cultured human skin fibroblasts (LD50 = 0.35 J/cm2) and still 10-fold more potent than ALA–PDT with green light (LD50 = 4.5 J/cm2). Its toxicity relied on the formation of singlet oxygen, as was shown employing modulators of singlet oxygen lifetime. In line with these data, strong activation of the stress kinase p38 was obtained in ALA-pretreated cells irradiated with UVA at doses two orders of magnitude lower than necessary for a comparable activation of p38 by UVA in control cells. Taken together, these data suggest UVA–ALA–PDT as a potentially interesting new approach in the photodynamic treatment of skin diseases.

Keywords: ALA, 5-aminolevulinic acid; DMEM, Dulbecco's modified Eagle's medium; DTT, dithiothreitol; HBSS, Hank's balanced salt solution; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; PDT, photodynamic therapy.

Journal Article.  3448 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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