title: Visible light generates oxidative DNA base modifications in high excess of strand breaks in mammalian cells.
abstract: The DNA damage induced by visible light in L1210 mouse leukaemia cells was analysed by an alkaline elution assay with specific repair endonucleases. DNA single-strand breaks and DNA modifications sensitive to FPG protein (formamidopyrimidine-DNA glycosylase), endonuclease III and exonuclease III were quantified in parallel. The light-induced cellular DNA damage was found to consist of many base modifications sensitive to FPG protein, which most probably are predominantly 7,8-dihydro-8-oxoguanine (8-hydroxyguanine) residues. Base modifications sensitive to endonuclease III are virtually absent. The yield of the FPG-sensitive base modifications is 10-fold higher than that of single-strand breaks plus AP sites (sites of base loss). The described ratios of the various modifications indicate that the damage most probably results from a reaction of DNA with singlet oxygen (type II reaction) or directly with an excited endogenous photosensitizer (type I reaction) and is not mediated by hydroxyl radicals. Experiments with cut-off filters indicate that wavelengths between 400 and 500 nm are responsible for most of the modifications. The FPG-sensitive base modifications are repaired efficiently (t1/2 approximately 1 h at 37 degrees C). This is perhaps why the light-induced DNA damage is apparently associated with only low mutagenicity.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Würzburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Pflaum
authors.forename: S
authors.initials: S
authors.lastname: Boiteux
authors.forename: B
authors.initials: B
authors.lastname: Epe
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000528:radiation effects; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D043382:DNA-Formamidopyrimidine Glycosylase; D007939:Leukemia L1210; D008027:Light; D051379:Mice; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen; D026082:Singlet Oxygen
chemical_list: D026082:Singlet Oxygen; D004247:DNA; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; D010100:Oxygen