Cadet J, Sage E, Douki T.. Ultraviolet radiation-mediated damage to cellular DNA. Mutat Res 571: 3-17

Laboratoire Lésions des Acides Nucléiques, Service de Chimie Inorganique et Biologique, CEA/DSM/Département de Recherche Fondamentale sur la Matière Condensée, CEA-Grenoble, Grenoble Cedex 9 F-38054, France.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis (Impact Factor: 3.68). 05/2005; 571(1-2):3-17. DOI: 10.1016/j.mrfmmm.2004.09.012
Source: PubMed


Emphasis is placed in this review article on recent aspects of the photochemistry of cellular DNA in which both the UVB and UVA components of solar radiation are implicated individually or synergistically. Interestingly, further mechanistic insights into the UV-induced formation of DNA photoproducts were gained from the application of new accurate and sensitive chromatographic and enzymic assays aimed at measuring base damage. Thus, each of the twelve possible dimeric photoproducts that are produced at the four main bipyrimidine sites can now be singled out as dinucleoside monophosphates that are enzymatically released from UV-irradiated DNA. This was achieved using a recently developed high-performance liquid chromatography-tandem mass spectrometry assay (HPLC-MS/MS) assay after DNA extraction and appropriate enzymic digestion. Interestingly, a similar photoproduct distribution pattern is observed in both isolated and cellular DNA upon exposure to low doses of either UVC or UVB radiation. This applies more specifically to the DNA of rodent and human cells, the cis-syn cyclobutadithymine being predominant over the two other main photolesions, namely thymine-cytosine pyrimidine (6-4) pyrimidone adduct and the related cyclobutyl dimer. UVA-irradiation was found to generate cyclobutane dimers at TT and to a lower extent at TC sites as a likely result of energy transfer mechanism involving still unknown photoexcited chromophore(s). Oxidative damage to DNA is also induced although less efficiently by UVA-mediated photosensitization processes that mostly involved 1O2 together with a smaller contribution of hydroxyl radical-mediated reactions through initially generated superoxide radicals.

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    • "The DNA repair of UVA-induced DNA damage occurs through three main mechanisms: (1) Photoreactivation, which involves the direct monomerization of CPDs and 6–4PPs by the action of photolyases enzymes in the presence of UVA/visible light; (2) Nucleotide Excision Repair (NER) which is critically important in the repair of UV-induced DNA lesion and is one of the most versatile and flexible repair systems found in most organisms; and (3) Base Excision Repair (BER) which acts on small DNA lesions such as oxidized bases, abasic sites and DNA single-strand breaks (Cadet et al., 2005; Rastogi et al., 2010). "
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    ABSTRACT: The increased incidence of solar ultraviolet radiation (UV) due to ozone depletion has been affecting both terrestrial and aquatic ecosystems and it may help to explain the enigmatic decline of amphibian populations in specific localities. In this work, influential events concerning the Antarctic ozone hole were identified in a dataset containing 35 years of ozone measurements over southern Brazil. The effects of environmental doses of UVB and UVA radiation were addressed on the morphology and development of Hypsiboas pulchellus tadpole (Anura: Hylidae), as well as on the induction of malformation after the conclusion of metamorphosis. These analyzes were complemented by the detection of micronucleus formation in blood cells. 72 ozone depletion events were identified from 1979 to 2013. Surprisingly, their yearly frequency increased three-fold during the last 17 years. The results clearly show that H. pulchellus tadpole are much more sensitive to UVB than UVA light, which reduces their survival and developmental rates. Additionally, the rates of micronucleus formation by UVB were considerably higher compared to UVA even after the activation of photolyases enzymes by a further photoreactivation treatment. Consequently, a higher occurrence of malformation was observed in UVB-irradiated individuals. These results demonstrate the severe genotoxic impact of UVB radiation on this treefrog species and its importance for further studies aimed to assess the impact of the increased levels of solar UVB radiation on declining species of the Hylidae family. Copyright © 2015 Elsevier Inc. All rights reserved.
    Ecotoxicology and Environmental Safety 05/2015; 118:190-198. DOI:10.1016/j.ecoenv.2015.04.029 · 2.76 Impact Factor
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    • "This dimerization distorts the DNA molecule, blocks the division and elongation of nucleic acids thus leading to cell death. Despite the well-known role of UVC irradiation as an antibacterial agent, its role to treat infections needs to be elucidated [102]. It is difficult to manage wound infections produced by multi drug resistant bacterial strains. "
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    ABSTRACT: Methicillin-resistant Staphylococcus aureus (MRSA) has become the most important drug-resistant microbial pathogen in countries throughout the world. Morbidity and mortality due to MRSA infections continue to increase despite efforts to improve infection control measures and to develop new antibiotics. Therefore alternative antimicrobial strategies that do not give rise to development of resistance are urgently required. A group of therapeutic interventions have been developed in the field of photomedicine with the common theme that they rely on electromagnetic radiation with wavelengths between 200 and 1000 nm broadly called "light". These techniques all use simple absorption of photons by specific chromophores to deliver the killing blow to microbial cells while leaving the surrounding host mammalian cells relatively unharmed. Photodynamic inactivation uses dyes called photosensitizers (PS) that bind specifically to MRSA cells and not host cells, and generate reactive oxygen species and singlet oxygen upon illumination. Sophisticated molecular strategies to target the PS to MRSA cells have been designed. Ultraviolet C radiation can damage microbial DNA without unduly harming host DNA. Blue light can excite endogenous porphyrins and flavins in MRSA cells that are not present in host cells. Near-infrared lasers can interfere with microbial membrane potentials without raising the temperature of the tissue. Taken together these innovative approaches towards harnessing the power of light suggest that the ongoing threat of MRSA may eventually be defeated.
    Current pharmaceutical design 03/2015; 21(16). DOI:10.2174/1381612821666150310102318 · 3.45 Impact Factor
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    • "The mechanism of DNA damage by ultraviolet radiation is well-defined in previous literature. Ultraviolet radiation usually causes the formation of pyrimidine dimers in DNA, but can also induce DNA damage through oxidative stress [44] [45]. There are virtually no studies available on the mechanisms of ammonium nitrate and ammonium sulfate induced DNA damage. "
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    ABSTRACT: Epidemiological studies have correlated exposure to ultraviolet-irradiated particulate matter with cardiovascular, respiratory, and lung diseases. This study investigated the DNA damage induced by two major inorganic particulate matter compounds found in diesel exhaust, ammonium nitrate and ammonium sulfate, on Burkitt's lymphoma (Raji) and hepatocellular carcinoma (HepG2) cell lines. We found a dose-dependent positive correlation of accumulated DNA damage at concentrations of ammonium nitrate (25μg/ml, 50μg/ml, 100μg/ml, 200μg/ml, 400μg/ml) with ultraviolet exposure (250J/m(2), 400J/m(2), 600J/m(2), 850J/m(2)), as measured by the comet assay in both cell lines. There was a significant difference between the treated ammonium nitrate samples and negative control samples in Raji and HepG2 cells (p<0.001). Apoptosis was shown in Raji and HepG2 cells when exposed to high concentrations of ammonium nitrate (200μg/ml and 400μg/ml) for 1h in samples without ultraviolet exposure, as assessed by the comet assay. However, the level of apoptosis greatly diminished after ultraviolet exposure at these concentrations. Over a 24h period, at intervals of 1, 4, 8, 12, 18, and 24h, we also observed that ammonium nitrate decreased viability in Raji and HepG2 cell lines and inhibited cell growth. Ammonium sulfate-induced DNA damage was minimal in both cell lines, but there remained a significant difference (p<0.05) between the ultraviolet radiation treated and negative control samples. These results indicate that the inorganic particulate compound, ammonium nitrate, induced DNA strand breaks at all concentrations, and indications of apoptosis at high concentrations in Raji and HepG2 cells, with ultraviolet radiation preventing apoptosis at high concentrations. We hypothesize that ultraviolet radiation may inhibit an essential cellular mechanism, possibly involving p53, thereby explaining this phenomenon. Further studies are necessary to characterize the roles of apoptosis inhibition induced by DNA damage caused by inorganic particulate matter.
    Mutation Research/Genetic Toxicology and Environmental Mutagenesis 09/2014; 771C:6-14. DOI:10.1016/j.mrgentox.2014.06.004 · 2.42 Impact Factor
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