Visible light (>395 nm) causes micronuclei formation in mammalian cells without generation of cyclobutane pyrimidine dimers.
Solar radiation gives rise to DNA damage in mammalian cells not only directly by excitation of DNA, which generates predominantly pyrimidine dimers, but also indirectly by the excitation of endogenous photosensitizers, which causes oxidative DNA modifications. The latter mechanism has a low quantum yield, but it is the only one proceeding in the visible range of the spectrum. To investigate its relevance for the genotoxicity of sunlight, we have analysed the generation of micronuclei associated with the induction of oxidative DNA damage by visible light in melanoma cells and primary human skin fibroblasts. Similar yields of light-induced oxidative DNA base modifications sensitive to the repair glycosylase Fpg (7,8-dihydro-8-oxoguanine and other oxidative purine modifications) were observed in the normal fibroblasts and the malignant melanoma cells of the same donor. When irradiations were carried out at intervals to compensate for a photodecomposition of the endogenous chromophore, a significant generation of micronuclei was observed in both cell types. Cyclobutane pyrimidine dimers could be excluded to be responsible for the micronuclei induction at wavelengths >395 nm. Experiments with a cut-off filter indicate that the ratio of pyrimidine dimers and Fpg-sensitive oxidative modifications in irradiated cells not only reflects the relative contributions of direct and indirect mechanisms, but is also similar to the ratio by which the two mechanisms contribute to the generation of the micronuclei. The results suggest that indirectly generated oxidative DNA modifications can contribute significantly to the adverse effects of sunlight.
Hoffmann-Dörr
Simone
S
Institute of Pharmacy, University of Mainz, Staudinger Weg 5, 55099 Mainz, Germany.
Greinert
Rüdiger
R
Volkmer
Beate
B
Epe
Bernd
B
D000818:Animals; D006801:Humans; D008027:Light; D008297:Male; D008545:Melanoma / Q000473:pathology / Q000648:ultrastructure; D015162:Micronucleus Tests; D008875:Middle Aged; D011740:Pyrimidine Dimers; D014407:Tumor Cells, Cultured
D011740:Pyrimidine Dimers