Identification of Possible Reactive Oxygen Species Involved in Ultraviolet Radiation-Induced Oxidative DNA Damage

Zhang, Xueshu; Rosenstein, Barry S.; Wang, Yan; Lebwohl, Mark; Wei, Huachen

doi:10.1016/s0891-5849(97)00126-3

Cited by 199 publications

(124 citation statements)

References 31 publications

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“…Indeed, we found that the majority of UV-induced mutations in CS-B cells were G:C→T:A mutations, a signature of 8-oxo-dG-induced mutagenesis (Fig. 3F), which can be caused by direct oxidation of DNA by UV and, more indirectly, by singlet oxygen formation in cells following UV irradiation (24)(25)(26). This result is consistent with increased mutagenesis resulting from deficient oxidative DNA-damage repair in CS cells.…”

Section: Cs Cells Fail To Demonstrate Elevated Subclonal Frequenciessupporting

confidence: 79%

Why Cockayne syndrome patients do not get cancer despite their DNA repair deficiency

Reid-Bayliss

Arron

Loeb

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Cockayne syndrome (CS) and xeroderma pigmentosum (XP) are human photosensitive diseases with mutations in the nucleotide excision repair (NER) pathway, which repairs DNA damage from UV exposure. CS is mutated in the transcription-coupled repair (TCR) branch of the NER pathway and exhibits developmental and neurological pathologies. The XP-C group of XP patients have mutations in the global genome repair (GGR) branch of the NER pathway and have a very high incidence of UV-induced skin cancer. Cultured cells from both diseases have similar sensitivity to UV-induced cytotoxicity, but CS patients have never been reported to develop cancer, although they often exhibit photosensitivity. Because cancers are associated with increased mutations, especially when initiated by DNA damage, we examined UV-induced mutagenesis in both XP-C and CS cells, using duplex sequencing for high-sensitivity mutation detection. Duplex sequencing detects rare mutagenic events, independent of selection and in multiple loci, enabling examination of all mutations rather than just those that confer major changes to a specific protein. We found telomerase-positive normal and CS-B cells had increased background mutation frequencies that decreased upon irradiation, purging the population of subclonal variants. Primary XP-C cells had increased UV-induced mutation frequencies compared with normal cells, consistent with their GGR deficiency. CS cells, in contrast, had normal levels of mutagenesis despite their TCR deficiency. The lack of elevated UV-induced mutagenesis in CS cells reveals that their TCR deficiency, although increasing cytotoxicity, is not mutagenic. Therefore the absence of cancer in CS patients results from the absence of UV-induced mutagenesis rather than from enhanced lethality.

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Section: Cs Cells Fail To Demonstrate Elevated Subclonal Frequenciessupporting

confidence: 79%

Why Cockayne syndrome patients do not get cancer despite their DNA repair deficiency

Reid-Bayliss

Arron

Loeb

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Recombinant adenovirus, Ad.IkBM, was used as the shuttle vector for expressing this inhibitor. In these studies, adenoviral constructs expressing the dominant negative mutant form of IkB (Ad.IkBM) or LacZ gene (Ad.CMVLacZ) were infected into Hela cells at different MOI values (10,50,250, 1000 particles per cell). The following day, Hela cells were UV irradiated and nuclear extracts were prepared 1 h after treatment (optimal timepoint for activation of NF-B).…”

Section: Uv Modulation Of Raav Transduction Is Not Controlled By Nf-bmentioning

confidence: 99%

Cellular redox state alters recombinant adeno-associated virus transduction through tyrosine phosphatase pathways

Şanlıoğlu

Engelhardt

1999

Gene Ther

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“…14 However, an imbalance between ROS-producing levels and the antioxidant defense is in favor of the former upon UV irradiation and leads to cytotoxicity by proteins, lipids and DNA oxidation both in vitro and in vivo. [15][16][17][18] It has been shown that UVA and UVB irradiation of murine skin results in impairment of enzymatic and non-enzymatic antioxidants. 5 In addition, several studies have demonstrated that an increase in antioxidant defense systems can reduce the deleterious effects of UV-induced ROS.…”

Section: Introductionmentioning

confidence: 99%

Protection of normal human reconstructed epidermis from UV by catalase overexpression

et al. 2006

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Reactive oxygen species (ROS) generated by ultraviolet (UV) irradiation are counterbalanced by endogenous antioxidant systems. To test the hypothesis of a novel photoprotective approach, we irradiated epidermis reconstructed with normal human keratinocytes overexpressing sustainably lentivirus-mediated catalase (CAT), copper/zinc superoxide dismutase (CuZnSOD) or manganese superoxide dismutase (MnSOD) enzymes. We found that following UVB irradiation there was a marked decrease in sunburn cell formation, caspase-3 activation and p53 accumulation in human reconstructed epidermis overexpressing CAT. Moreover, UVA-induced hypertrophy and DNA oxidation (8-oxodeoxyguanosine) were decreased by CAT overexpression. These effects were not achieved by overexpression of CuZnSOD or MnSOD. In conclusion, vector-mediated CAT overexpression could be a promising photoprotective tool against deleterious effects of UV irradiation such skin cancer especially in monogenic/polygenic photosensitive disorders characterized by ROS accumulation.

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Identification of Possible Reactive Oxygen Species Involved in Ultraviolet Radiation-Induced Oxidative DNA Damage

Cited by 199 publications

References 31 publications

Why Cockayne syndrome patients do not get cancer despite their DNA repair deficiency

Why Cockayne syndrome patients do not get cancer despite their DNA repair deficiency

Cellular redox state alters recombinant adeno-associated virus transduction through tyrosine phosphatase pathways

Protection of normal human reconstructed epidermis from UV by catalase overexpression

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