Visible light generates oxidative DNA base modifications in high excess of strand breaks in mammalian cells.
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.
Pflaum
M
M
Institute of Pharmacology and Toxicology, University of Würzburg, Germany.
Boiteux
S
S
Epe
B
B
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
D026082:Singlet Oxygen; D004247:DNA; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; D010100:Oxygen