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      Chronic irradiation with 222-nm UVC light induces neither DNA damage nor epidermal lesions in mouse skin, even at high doses

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          Abstract

          Surgical site infections (SSIs) represent an important clinical problem associated with increased levels of surgical morbidity and mortality. UVC irradiation during surgery has been considered to represent a possible strategy to prevent the development of SSI. 254-nm UVC induces marked levels of DNA damage by generating cyclobutyl pyrimidine dimers (CPD) in microorganisms. However, this effect is elicited not only in microorganisms, but also in human cells, and chronic exposure to 254-nm UVC has been established to represent a human health hazard. In contrast, despite short wavelength-UVC light, especially 222-nm UVC, having been demonstrated to elicit a bactericidal effect, single irradiation with a high dose of 222-nm UVC energy has been reported to not induce mutagenic or cytotoxic DNA lesions in mammalian cells. However, the effect of chronic irradiation with a high dose of 222-nm UVC to mammalian cells has not been determined. In this study, it was demonstrated that large numbers of CPD-expressing cells were induced in the epidermis of mice following treatment with a small amount of single exposure 254-nm UVC, and then less than half of these cells reduced within 24 h. Chronic 254-nm UVC irradiation was revealed to induce sunburn and desquamation in mouse skin. Histological analysis demonstrated that small numbers of CPD-expressing cells were detected only in hyperkeratotic stratum corneum after chronic irradiation with a high dose of 254-nm UVC, and that significant hyperplasia and intercellular edema were also induced in the epidermis of mice. In contrast, chronic irradiation with 222-nm UVC light was revealed not to induce mutagenic or cytotoxic effects in the epidermis of mice. These results indicated that 222-nm UVC light emitted from the lamp apparatus (or device), which was designed to attenuate harmful light present in wavelengths of more than 230 nm, represents a promising tool for the reduction of SSI incidence in patients and hospital staff.

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          Molecular Mechanisms of Ultraviolet Radiation-Induced DNA Damage and Repair

          DNA is one of the prime molecules, and its stability is of utmost importance for proper functioning and existence of all living systems. Genotoxic chemicals and radiations exert adverse effects on genome stability. Ultraviolet radiation (UVR) (mainly UV-B: 280–315 nm) is one of the powerful agents that can alter the normal state of life by inducing a variety of mutagenic and cytotoxic DNA lesions such as cyclobutane-pyrimidine dimers (CPDs), 6-4 photoproducts (6-4PPs), and their Dewar valence isomers as well as DNA strand breaks by interfering the genome integrity. To counteract these lesions, organisms have developed a number of highly conserved repair mechanisms such as photoreactivation, base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR). Additionally, double-strand break repair (by homologous recombination and nonhomologous end joining), SOS response, cell-cycle checkpoints, and programmed cell death (apoptosis) are also operative in various organisms with the expense of specific gene products. This review deals with UV-induced alterations in DNA and its maintenance by various repair mechanisms.
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            Mutations induced by ultraviolet light.

            The different ultraviolet (UV) wavelength components, UVA (320-400 nm), UVB (280-320 nm), and UVC (200-280 nm), have distinct mutagenic properties. A hallmark of UVC and UVB mutagenesis is the high frequency of transition mutations at dipyrimidine sequences containing cytosine. In human skin cancers, about 35% of all mutations in the p53 gene are transitions at dipyrimidines within the sequence 5'-TCG and 5'-CCG, and these are localized at several mutational hotspots. Since 5'-CG sequences are methylated along the p53 coding sequence in human cells, these mutations may be derived from sunlight-induced pyrimidine dimers forming at sequences that contain 5-methylcytosine. Cyclobutane pyrimidine dimers (CPDs) form preferentially at dipyrimidines containing 5-methylcytosine when cells are irradiated with UVB or sunlight. In order to define the contribution of 5-methylcytosine to sunlight-induced mutations, the lacI and cII transgenes in mouse fibroblasts were used as mutational targets. After 254 nm UVC irradiation, only 6-9% of the base substitutions were at dipyrimidines containing 5-methylcytosine. However, 24-32% of the solar light-induced mutations were at dipyrimidines that contain 5-methylcytosine and most of these mutations were transitions. Thus, CPDs forming preferentially at dipyrimidines with 5-methylcytosine are responsible for a considerable fraction of the mutations induced by sunlight in mammalian cells. Using mouse cell lines harboring photoproduct-specific photolyases and mutational reporter genes, we showed that CPDs (rather than 6-4 photoproducts or other lesions) are responsible for the great majority of UVB-induced mutations. An important component of UVB mutagenesis is the deamination of cytosine and 5-methylcytosine within CPDs. The mutational specificity of long-wave UVA (340-400 nm) is distinct from that of the shorter wavelength UV and is characterized mainly by G to T transversions presumably arising through mechanisms involving oxidized DNA bases. We also discuss the role of DNA damage-tolerant DNA polymerases in UV lesion bypass and mutagenesis.
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              Far-UVC light: A new tool to control the spread of airborne-mediated microbial diseases

              Airborne-mediated microbial diseases such as influenza and tuberculosis represent major public health challenges. A direct approach to prevent airborne transmission is inactivation of airborne pathogens, and the airborne antimicrobial potential of UVC ultraviolet light has long been established; however, its widespread use in public settings is limited because conventional UVC light sources are both carcinogenic and cataractogenic. By contrast, we have previously shown that far-UVC light (207–222 nm) efficiently inactivates bacteria without harm to exposed mammalian skin. This is because, due to its strong absorbance in biological materials, far-UVC light cannot penetrate even the outer (non living) layers of human skin or eye; however, because bacteria and viruses are of micrometer or smaller dimensions, far-UVC can penetrate and inactivate them. We show for the first time that far-UVC efficiently inactivates airborne aerosolized viruses, with a very low dose of 2 mJ/cm2 of 222-nm light inactivating >95% of aerosolized H1N1 influenza virus. Continuous very low dose-rate far-UVC light in indoor public locations is a promising, safe and inexpensive tool to reduce the spread of airborne-mediated microbial diseases.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: ValidationRole: Writing – original draft
                Role: Writing – original draft
                Role: ConceptualizationRole: InvestigationRole: Writing – original draft
                Role: ConceptualizationRole: Writing – original draft
                Role: ConceptualizationRole: Project administrationRole: SupervisionRole: Writing – original draft
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                25 July 2018
                2018
                : 13
                : 7
                : e0201259
                Affiliations
                [1 ] Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
                [2 ] Institute for Animal Experimentation, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
                [3 ] Department of Biopolymer and Health Science, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
                [4 ] Ushio Inc., Chiyoda-ku, Tokyo, Japan
                Georgetown University, UNITED STATES
                Author notes

                Competing Interests: I have read the journal's policy and the authors of this manuscript Yukihiro Morimoto and Tatsushi Igarashi have the following competing interests: Yukihiro Morimoto and Tatsushi Igarashi are provided support in the form of salaries from Ushio Inc., Tokyo, Japan. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0001-8807-7384
                http://orcid.org/0000-0002-9583-8919
                Article
                PONE-D-18-11468
                10.1371/journal.pone.0201259
                6059456
                30044862
                61a57c30-2808-45d4-b0d2-66ac94e2aa51
                © 2018 Narita et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 16 April 2018
                : 11 July 2018
                Page count
                Figures: 4, Tables: 0, Pages: 9
                Funding
                This work was supported by USHIO Inc., Tokyo, Japan. The funder provided support in the form of salaries for authors [Y. M. and T. I.] but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Physical sciences
                Physics
                Electromagnetic radiation
                Light
                Ultraviolet radiation
                Ultraviolet C
                Biology and Life Sciences
                Anatomy
                Integumentary System
                Skin
                Epidermis
                Medicine and Health Sciences
                Anatomy
                Integumentary System
                Skin
                Epidermis
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Research and Analysis Methods
                Experimental Organism Systems
                Model Organisms
                Mouse Models
                Research and Analysis Methods
                Model Organisms
                Mouse Models
                Research and Analysis Methods
                Experimental Organism Systems
                Animal Models
                Mouse Models
                Biology and life sciences
                Organisms
                Bacteria
                Staphylococcus
                Staphylococcus aureus
                Methicillin-resistant Staphylococcus aureus
                Biology and life sciences
                Microbiology
                Medical microbiology
                Microbial pathogens
                Bacterial pathogens
                Staphylococcus
                Staphylococcus aureus
                Methicillin-resistant Staphylococcus aureus
                Medicine and health sciences
                Pathology and laboratory medicine
                Pathogens
                Microbial pathogens
                Bacterial pathogens
                Staphylococcus
                Staphylococcus aureus
                Methicillin-resistant Staphylococcus aureus
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Lesions
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Lesions
                Biology and Life Sciences
                Anatomy
                Histology
                Medicine and Health Sciences
                Anatomy
                Histology
                Biology and life sciences
                Genetics
                DNA
                DNA damage
                Biology and life sciences
                Biochemistry
                Nucleic acids
                DNA
                DNA damage
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                All relevant data are within the paper.

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