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 endonu cleases. DNA single-strand breaks and DNA modifications sensitive to F PG protein (formamidopyrimidine-DNA glycosylase), endonuclease III and exonuclease m 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-ox oguanine (8-hydroxyguanine) residues. Base modifications sensitive to endonuclease m are virtually absent. The yield of the FPG-sensitive ba se modifications is III-fold higher than that of single-strand breaks plus AP sites (sites of base loss). The described ratios of the variou s modifications indicate that the damage most probably results from a reaction of DNA with singlet oxygen (type II reaction) or directly wit h an excited endogenous photosensitizer (type I reaction) and is not m ediated by hydroxyl radicals. Experiments with cut-off filters indicat e that wavelengths between 400 and 500 nm are responsible for most of the modifications. The FPG-sensitive base modifications are repaired e fficiently (t1/2 approximately 1 h at 37 degrees C). This is perhaps w hy the light-induced DNA damage is apparently associated with only low mutagenicity.