title: Blue light induces mitochondrial DNA damage and free radical production in epithelial cells.
abstract: Exposure of biological chromophores to ultraviolet radiation can lead to photochemical damage. However, the role of visible light, particularly in the blue region of the spectrum, has been largely ignored. To test the hypothesis that blue light is toxic to non-pigmented epithelial cells, confluent cultures of human primary retinal epithelial cells were exposed to visible light (390-550 nm at 2.8 milliwatts/cm2) for up to 6 h. A small loss of mitochondrial respiratory activity was observed at 6 h compared with dark-maintained cells, and this loss became greater with increasing time. To investigate the mechanism of cell loss, the damage to mitochondrial and nuclear genes was assessed using the quantitative PCR. Light exposure significantly damaged mitochondrial DNA at 3 h (0.7 lesion/10 kb DNA) compared with dark-maintained controls. However, by 6 h of light exposure, the number of lesions was decreased in the surviving cells, indicating DNA repair. Isolated mitochondria exposed to light generated singlet oxygen, superoxide anion, and the hydroxyl radical. Antioxidants confirmed the superoxide anion to be the primary species responsible for the mitochondrial DNA lesions. The effect of lipofuscin, a photoinducible intracellular generator of reactive oxygen intermediates, was investigated for comparison. Exposure of lipofuscin-containing cells to visible light caused an increase in both mitochondrial and nuclear DNA lesions compared with non-pigmented cells. We conclude that visible light can cause cell dysfunction through the action of reactive oxygen species on DNA and that this may contribute to cellular aging, age-related pathologies, and tumorigenesis.
authors.affiliation: Retina Foundation of the Southwest, Dallas, Texas 75231, USA. bgodley@retinafoundation.org
authors.forename: Bernard F
authors.initials: BF
authors.lastname: Godley
authors.forename: Farrukh A
authors.initials: FA
authors.lastname: Shamsi
authors.forename: Fong-Qi
authors.initials: FQ
authors.lastname: Liang
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Jarrett
authors.forename: Sallyanne
authors.initials: S
authors.lastname: Davies
authors.forename: Mike
authors.initials: M
authors.lastname: Boulton
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D002498:Centrifugation; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology*; D005609:Free Radicals; D006801:Humans; D017665:Hydroxyl Radical; D008027:Light; D008062:Lipofuscin / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D016133:Polymerase Chain Reaction; D017382:Reactive Oxygen Species; D012160:Retina / Q000166:cytology; D013481:Superoxides / Q000378:metabolism; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: D000975:Antioxidants; D004272:DNA, Mitochondrial; D005609:Free Radicals; D008062:Lipofuscin; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D013481:Superoxides; D017665:Hydroxyl Radical; D004247:DNA; C022616:thiazolyl blue; D010100:Oxygen