[Biomarkers of radiation-induced DNA repair processes].

PubMed

Vallard, Alexis; Rancoule, Chloé; Guy, Jean-Baptiste; Espenel, Sophie; Sauvaigo, Sylvie; Rodriguez-Lafrasse, Claire; Magné, Nicolas

2017-11-01

The identification of DNA repair biomarkers is of paramount importance. Indeed, it is the first step in the process of modulating radiosensitivity and radioresistance. Unlike tools of detection and measurement of DNA damage, DNA repair biomarkers highlight the variations of DNA damage responses, depending on the dose and the dose rate. The aim of the present review is to describe the main biomarkers of radiation-induced DNA repair. We will focus on double strand breaks (DSB), because of their major role in radiation-induced cell death. The most important DNA repair biomarkers are DNA damage signaling proteins, with ATM, DNA-PKcs, 53BP1 and γ-H2AX. They can be analyzed either using immunostaining, or using lived cell imaging. However, to date, these techniques are still time and money consuming. The development of "omics" technologies should lead the way to new (and usable in daily routine) DNA repair biomarkers. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Molecular response of nasal mucosa to therapeutic exposure to broad-band ultraviolet radiation

PubMed Central

Mitchell, David; Paniker, Lakshmi; Sanchez, Guillermo; Bella, Zsolt; Garaczi, Edina; Szell, Marta; Hamid, Qutayba; Kemeny, Lajos; Koreck, Andrea

2010-01-01

Abstract Ultraviolet radiation (UVR) phototherapy is a promising new treatment for inflammatory airway diseases. However, the potential carcinogenic risks associated with this treatment are not well understood. UV-specific DNA photoproducts were used as biomarkers to address this issue. Radioimmunoassay was used to quantify cyclobutane pyrimidine dimers (CPDs) and (6–4) photoproducts in DNA purified from two milieus: nasal mucosa samples from subjects exposed to intranasal phototherapy and human airway (EpiAirway™) and human skin (EpiDerm™) tissue models. Immunohistochemistry was used to detect CPD formation and persistence in human nasal biopsies and human tissue models. In subjects exposed to broadband ultraviolet radiation, DNA damage frequencies were determined prior to as well as immediately after treatment and at increasing times post-treatment. We observed significant levels of DNA damage immediately after treatment and efficient removal of the damage within a few days. No residual damage was observed in human subjects exposed to multiple UVB treatments several weeks after the last treatment. To better understand the molecular response of the nasal epithelium to DNA damage, parallel experiments were conducted in EpiAirway and EpiDerm model systems. Repair rates in these two tissues were very similar and comparable to that observed in human skin. The data suggest that the UV-induced DNA damage response of respiratory epithelia is very similar to that of the human epidermis and that nasal mucosa is able to efficiently repair UVB induced DNA damage. PMID:18671762

Ultraviolet-B-induced DNA damage and ultraviolet-B tolerance mechanisms in species with different functional groups coexisting in subalpine moorlands.

PubMed

Wang, Qing-Wei; Kamiyama, Chiho; Hidema, Jun; Hikosaka, Kouki

2016-08-01

High doses of ultraviolet-B (UV-B; 280-315 nm) radiation can have detrimental effects on plants, and especially damage their DNA. Plants have DNA repair and protection mechanisms to prevent UV-B damage. However, it remains unclear how DNA damage and tolerance mechanisms vary among field species. We studied DNA damage and tolerance mechanisms in 26 species with different functional groups coexisting in two moorlands at two elevations. We collected current-year leaves in July and August, and determined accumulation of cyclobutane pyrimidine dimer (CPD) as UV-B damage and photorepair activity (PRA) and concentrations of UV-absorbing compounds (UACs) and carotenoids (CARs) as UV-B tolerance mechanisms. DNA damage was greater in dicot than in monocot species, and higher in herbaceous than in woody species. Evergreen species accumulated more CPDs than deciduous species. PRA was higher in Poaceae than in species of other families. UACs were significantly higher in woody than in herbaceous species. The CPD level was not explained by the mechanisms across species, but was significantly related to PRA and UACs when we ignored species with low CPD, PRA and UACs, implying the presence of another effective tolerance mechanism. UACs were correlated negatively with PRA and positively with CARs. Our results revealed that UV-induced DNA damage significantly varies among native species, and this variation is related to functional groups. DNA repair, rather than UV-B protection, dominates in UV-B tolerance in the field. Our findings also suggest that UV-B tolerance mechanisms vary among species under evolutionary trade-off and synergism.

Jatropha curcas leaf and bark fractions protect against ultraviolet radiation-B induced DNA damage in human peripheral blood lymphocytes.

PubMed

Sundari, J; Selvaraj, R; Rajendra Prasad, N; Elumalai, R

2013-11-01

The present study is conducted to investigate the antioxidant potential of Jatropha curcas root bark extract (RB4 fraction) and leaf extract (L1 fraction), and to study their effects on UVB-radiation-induced DNA damage in cultured human blood lymphocytes. In this study, J. curcas showed strong antioxidant property in different free radical scavenging systems. Both the fractions effectively scavenged hydroxyl (OH), superoxide anion (O₂(·-)), 1,1-diphenyl-2-picrylhydrazyl (DPPH·) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid radical cation (ABTS(·+)) in a concentration-dependent manner. The IC₅₀ (Inhibitory Concentration 50) values of J. curcas fractions were compared to standard ascorbic acid used in this study. The antioxidant potential of a compound was directly proportional to the photoprotective effect. In this study, human peripheral blood lymphocytes (HPBL) were exposed to UVB-radiation and there was an increase in comet attributes (% tail DNA, tail length, tail movement and Olive tail moment). Jatropha curcas RB4 fraction and L1 fraction treatment before UVB-irradiation significantly decreased the % tail DNA, tail length, tail moment and Olive tail moment in irradiated HPBL. These results suggested that J. curcas exhibited strong antioxidant property and RB4 and L1 fractions protected UVB-radiation-induced DNA damage in HPBL. Copyright © 2013 Elsevier B.V. All rights reserved.

Melanocortin 1 receptor genotype: an important determinant of the damage response of melanocytes to ultraviolet radiation

PubMed Central

Kadekaro, Ana Luisa; Leachman, Sancy; Kavanagh, Renny J.; Swope, Viki; Cassidy, Pamela; Supp, Dorothy; Sartor, Maureen; Schwemberger, Sandy; Babcock, George; Wakamatsu, Kazumasa; Ito, Shosuke; Koshoffer, Amy; Boissy, Raymond E.; Manga, Prashiela; Sturm, Richard A.; Abdel-Malek, Zalfa A.

2010-01-01

The melanocortin 1 receptor gene is a main determinant of human pigmentation, and a melanoma susceptibility gene, because its variants that are strongly associated with red hair color increase melanoma risk. To test experimentally the association between melanocortin 1 receptor genotype and melanoma susceptibility, we compared the responses of primary human melanocyte cultures naturally expressing different melanocortin 1 receptor variants to α-melanocortin and ultraviolet radiation. We found that expression of 2 red hair variants abolished the response to α-melanocortin and its photoprotective effects, evidenced by lack of functional coupling of the receptor, and absence of reduction in ultraviolet radiation-induced hydrogen peroxide generation or enhancement of repair of DNA photoproducts, respectively. These variants had different heterozygous effects on receptor function. Microarray data confirmed the observed differences in responses of melanocytes with functional vs. nonfunctional receptor to α-melanocortin and ultraviolet radiation, and identified DNA repair and antioxidant genes that are modulated by α-melanocortin. Our findings highlight the molecular mechanisms by which the melanocortin 1 receptor genotype controls genomic stability of and the mutagenic effect of ultraviolet radiation on human melanocytes.—Kadekaro, A. L., Leachman, S., Kavanagh, R. J., Swope, V., Cassidy, P., Supp, D., Sartor, M., Schwemberger, S., Babcock, G., Wakamatsu, K., Ito, S., Koshoffer, A., Boissy, R. E., Manga, P., Sturm, R. A., Abdel-Malek, Z. A. Melanocortin 1 receptor genotype: an important determinant of the damage response of melanocytes to ultraviolet radiation. PMID:20519635

Apigenin prevents ultraviolet-B radiation induced cyclobutane pyrimidine dimers formation in human dermal fibroblasts.

PubMed

Britto, S Mary; Shanthakumari, D; Agilan, B; Radhiga, T; Kanimozhi, G; Prasad, N Rajendra

2017-09-01

Exposure to solar ultraviolet-B (UVB) radiation leads to the formation of cyclobutane pyrimidine dimers (CPDs). We investigated the protective effect of apigenin against UVB-induced CPDs formation in human dermal fibroblasts cells (HDFa). For this purpose, HDFa cells were treated with apigenin (15μM) prior to UVB irradiation (20mJ/cm 2 ); DNA damage and subsequent molecular end points were observed. Exposure to UVB radiation increased significant CPDs formation in HDFa cells and the frequencies of CPDs were reduced by treatment with apigenin (15μM). UVB-induced CPDs downregulates the expression of nucleotide excision repair (NER) genes such as xeroderma pigmentosum complementation group C, B, G and F (XPC, XPB, XPG and XPF), transcription factor II human (TFIIH) and excision repair cross-complementation group 1 (ERCC1) in HDFa cells. Conversely, apigenin treatment restored UVB-induced loss of NER proteins in HDFa cells, which indicates its preventive effect against CPDs formation. Besides, single low dose UVB-exposure induced nuclear fragmentation, apoptotic frequency and apoptotic proteins expression (Bax and Caspase-3) have been prevented by the apigenin pretreatment. Furthermore, apigenin exhibits strong UV absorbance property and showed 10.08 SPF value. Thus, apigenin can protect skin cells against UVB-induced CPDs formation probably through its sunscreen effect. Hence, apigenin can be considered as an effective protective agent against UV induced skin damages. Copyright © 2017 Elsevier B.V. All rights reserved.

Systematic identification of DNA variants associated with ultraviolet radiation using a novel Geographic-Wide Association Study (GeoWAS).

PubMed

Hsu, Irving; Chen, Rong; Ramesh, Aditya; Corona, Erik; Kang, Hyunseok Peter; Ruau, David; Butte, Atul J

2013-06-20

Long-term environmental variables are widely understood to play important roles in DNA variation. Previously, clinical studies examining the impacts of these variables on the human genome were localized to a single country, and used preselected DNA variants. Furthermore, clinical studies or surveys are either not available or difficult to carry out for developing countries. A systematic approach utilizing bioinformatics to identify associations among environmental variables, genetic variation, and diseases across various geographical locations is needed but has been lacking. Using a novel Geographic-Wide Association Study (GeoWAS) methodology, we identified Single Nucleotide Polymorphisms (SNPs) in the Human Genome Diversity Project (HGDP) with population allele frequencies associated geographical ultraviolet radiation exposure, and then assessed the diseases known to be assigned with these SNPs. 2,857 radiation SNPs were identified from over 650,000 SNPs in 52 indigenous populations across the world. Using a quantitative disease-SNP database curated from 5,065 human genetic papers, we identified disease associations with those radiation SNPs. The correlation of the rs16891982 SNP in the SLC45A2 gene with melanoma was used as a case study for analysis of disease risk, and the results were consistent with the incidence and mortality rates of melanoma in published scientific literature. Finally, by analyzing the ontology of genes in which the radiation SNPs were significantly enriched, potential associations between SNPs and neurological disorders such as Alzheimer's disease were hypothesized. A systematic approach using GeoWAS has enabled us to identify DNA variation associated with ultraviolet radiation and their connections to diseases such as skin cancers. Our analyses have led to a better understating at the genetic level of why certain diseases are more predominant in specific geographical locations, due to the interactions between environmental variables such

Effect of DNA-injuring agents on B. stearothermophilus. Report 1. High resistance of B. stearothermophilus to N-nitroso-N-methylurea, ultraviolet and gamma radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gainullina, S.M.; Gumanova, A.V.; Vinogradova, N.A.

1978-01-01

The effects of DNA-attacking agents on thermophilic microorganisms were investigated. Bacillus stearothermophilus were treated with N-nitroso-N-methylurea, ultraviolet radiation or gamma radiation. Survival curves were plotted.

Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation

NASA Technical Reports Server (NTRS)

Sutherland, B. M.; Bennett, P. V.; Sidorkina, O.; Laval, J.; Lowenstein, D. I. (Principal Investigator)

2000-01-01

Clustered DNA damages-two or more closely spaced damages (strand breaks, abasic sites, or oxidized bases) on opposing strands-are suspects as critical lesions producing lethal and mutagenic effects of ionizing radiation. However, as a result of the lack of methods for measuring damage clusters induced by ionizing radiation in genomic DNA, neither the frequencies of their production by physiological doses of radiation, nor their repairability, nor their biological effects are known. On the basis of methods that we developed for quantitating damages in large DNAs, we have devised and validated a way of measuring ionizing radiation-induced clustered lesions in genomic DNA, including DNA from human cells. DNA is treated with an endonuclease that induces a single-strand cleavage at an oxidized base or abasic site. If there are two closely spaced damages on opposing strands, such cleavage will reduce the size of the DNA on a nondenaturing gel. We show that ionizing radiation does induce clustered DNA damages containing abasic sites, oxidized purines, or oxidized pyrimidines. Further, the frequency of each of these cluster classes is comparable to that of frank double-strand breaks; among all complex damages induced by ionizing radiation, double-strand breaks are only about 20%, with other clustered damage constituting some 80%. We also show that even low doses (0.1-1 Gy) of high linear energy transfer ionizing radiation induce clustered damages in human cells.

Using DNA origami nanostructures to determine absolute cross sections for UV photon-induced DNA strand breakage.

PubMed

Vogel, Stefanie; Rackwitz, Jenny; Schürman, Robin; Prinz, Julia; Milosavljević, Aleksandar R; Réfrégiers, Matthieu; Giuliani, Alexandre; Bald, Ilko

2015-11-19

We have characterized ultraviolet (UV) photon-induced DNA strand break processes by determination of absolute cross sections for photoabsorption and for sequence-specific DNA single strand breakage induced by photons in an energy range from 6.50 to 8.94 eV. These represent the lowest-energy photons able to induce DNA strand breaks. Oligonucleotide targets are immobilized on a UV transparent substrate in controlled quantities through attachment to DNA origami templates. Photon-induced dissociation of single DNA strands is visualized and quantified using atomic force microscopy. The obtained quantum yields for strand breakage vary between 0.06 and 0.5, indicating highly efficient DNA strand breakage by UV photons, which is clearly dependent on the photon energy. Above the ionization threshold strand breakage becomes clearly the dominant form of DNA radiation damage, which is then also dependent on the nucleotide sequence.

Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis in melanoma

NASA Astrophysics Data System (ADS)

Bald, Tobias; Quast, Thomas; Landsberg, Jennifer; Rogava, Meri; Glodde, Nicole; Lopez-Ramos, Dorys; Kohlmeyer, Judith; Riesenberg, Stefanie; van den Boorn-Konijnenberg, Debby; Hömig-Hölzel, Cornelia; Reuten, Raphael; Schadow, Benjamin; Weighardt, Heike; Wenzel, Daniela; Helfrich, Iris; Schadendorf, Dirk; Bloch, Wilhelm; Bianchi, Marco E.; Lugassy, Claire; Barnhill, Raymond L.; Koch, Manuel; Fleischmann, Bernd K.; Förster, Irmgard; Kastenmüller, Wolfgang; Kolanus, Waldemar; Hölzel, Michael; Gaffal, Evelyn; Tüting, Thomas

2014-03-01

Intermittent intense ultraviolet (UV) exposure represents an important aetiological factor in the development of malignant melanoma. The ability of UV radiation to cause tumour-initiating DNA mutations in melanocytes is now firmly established, but how the microenvironmental effects of UV radiation influence melanoma pathogenesis is not fully understood. Here we report that repetitive UV exposure of primary cutaneous melanomas in a genetically engineered mouse model promotes metastatic progression, independent of its tumour-initiating effects. UV irradiation enhanced the expansion of tumour cells along abluminal blood vessel surfaces and increased the number of lung metastases. This effect depended on the recruitment and activation of neutrophils, initiated by the release of high mobility group box 1 (HMGB1) from UV-damaged epidermal keratinocytes and driven by Toll-like receptor 4 (TLR4). The UV-induced neutrophilic inflammatory response stimulated angiogenesis and promoted the ability of melanoma cells to migrate towards endothelial cells and use selective motility cues on their surfaces. Our results not only reveal how UV irradiation of epidermal keratinocytes is sensed by the innate immune system, but also show that the resulting inflammatory response catalyses reciprocal melanoma-endothelial cell interactions leading to perivascular invasion, a phenomenon originally described as angiotropism in human melanomas by histopathologists. Angiotropism represents a hitherto underappreciated mechanism of metastasis that also increases the likelihood of intravasation and haematogenous dissemination. Consistent with our findings, ulcerated primary human melanomas with abundant neutrophils and reactive angiogenesis frequently show angiotropism and a high risk for metastases. Our work indicates that targeting the inflammation-induced phenotypic plasticity of melanoma cells and their association with endothelial cells represent rational strategies to specifically interfere

DNA Repair and Photoprotection: Mechanisms of Overcoming Environmental Ultraviolet Radiation Exposure in Halophilic Archaea

PubMed Central

Jones, Daniel L.; Baxter, Bonnie K.

2017-01-01

Halophilic archaea push the limits of life at several extremes. In particular, they are noted for their biochemical strategies in dealing with osmotic stress, low water activity and cycles of desiccation in their hypersaline environments. Another feature common to their habitats is intense ultraviolet (UV) radiation, which is a challenge that microorganisms must overcome. The consequences of high UV exposure include DNA lesions arising directly from bond rearrangement of adjacent bipyrimidines, or indirectly from oxidative damage, which may ultimately result in mutation and cell death. As such, these microorganisms have evolved a number of strategies to navigate the threat of DNA damage, which we differentiate into two categories: DNA repair and photoprotection. Photoprotection encompasses damage avoidance strategies that serve as a “first line of defense,” and in halophilic archaea include pigmentation by carotenoids, mechanisms of oxidative damage avoidance, polyploidy, and genomic signatures that make DNA less susceptible to photodamage. Photolesions that do arise are addressed by a number of DNA repair mechanisms that halophilic archaea efficiently utilize, which include photoreactivation, nucleotide excision repair, base excision repair, and homologous recombination. This review seeks to place DNA damage, repair, and photoprotection in the context of halophilic archaea and the solar radiation of their hypersaline environments. We also provide new insight into the breadth of strategies and how they may work together to produce remarkable UV-resistance for these microorganisms. PMID:29033920

DNA Repair and Photoprotection: Mechanisms of Overcoming Environmental Ultraviolet Radiation Exposure in Halophilic Archaea.

PubMed

Jones, Daniel L; Baxter, Bonnie K

2017-01-01

Halophilic archaea push the limits of life at several extremes. In particular, they are noted for their biochemical strategies in dealing with osmotic stress, low water activity and cycles of desiccation in their hypersaline environments. Another feature common to their habitats is intense ultraviolet (UV) radiation, which is a challenge that microorganisms must overcome. The consequences of high UV exposure include DNA lesions arising directly from bond rearrangement of adjacent bipyrimidines, or indirectly from oxidative damage, which may ultimately result in mutation and cell death. As such, these microorganisms have evolved a number of strategies to navigate the threat of DNA damage, which we differentiate into two categories: DNA repair and photoprotection. Photoprotection encompasses damage avoidance strategies that serve as a "first line of defense," and in halophilic archaea include pigmentation by carotenoids, mechanisms of oxidative damage avoidance, polyploidy, and genomic signatures that make DNA less susceptible to photodamage. Photolesions that do arise are addressed by a number of DNA repair mechanisms that halophilic archaea efficiently utilize, which include photoreactivation, nucleotide excision repair, base excision repair, and homologous recombination. This review seeks to place DNA damage, repair, and photoprotection in the context of halophilic archaea and the solar radiation of their hypersaline environments. We also provide new insight into the breadth of strategies and how they may work together to produce remarkable UV-resistance for these microorganisms.

Lethal cellular changes induced by near ultraviolet radiation.

PubMed

Tyrrell, R M

1979-01-01

There is clear evidence that significant quantities of lesions are induced in DNA by near-UV radiation and that these lesions, although susceptible to repair, may lead to cell death because of the simultaneous disruption of DNA repair systems by the same wavelengths. No particular DNA lesion can be linked to cell death in wild type strains. However, there are good grounds for speculating that a type of near-UV lesion exists which is rapidly "fixed" as a lethal event in cells as a result of the oxygen-dependent disruption of repair. There is a strong indication that the relative ability of various near-UV wavelengths to sensitize cells to heat, chemicals or other radiations is directly related to their efficiency in disrupting DNA repair systems in general. Some important specific questions remain. For example, it is important to ask why breaks formed at 365 nm and 405 nm, although apparently requiring a pol dependent pathway for their repair, do not produce the predicted lethal biological action in the strains tested. In general terms it is hoped to provide more comprehensive physico-chemical data in support of, or contradicting, the proposed model.

DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENTIAL FLUORESCENCE ASSAY

EPA Science Inventory

A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposur...

DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENNTIAL FLUORESENCE ASSAY

EPA Science Inventory

A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposures...

Are there mechanistic differences between ultraviolet and visible radiation induced skin pigmentation?

PubMed

Ramasubramaniam, Rajagopal; Roy, Arindam; Sharma, Bharati; Nagalakshmi, Surendra

2011-12-01

Most of the studies on sunlight-induced pigmentation of skin are mainly focused on ultraviolet (UV) radiation-induced pigmentation and ways to prevent it. Recent studies have shown that the visible component of sunlight can also cause significant skin pigmentation. In the current study, the extent of pigmentation induced by UV and visible regions of sunlight in subjects with Fitzpatrick skin type IV-V was measured and compared with pigmentation induced by total sunlight. The immediate pigment darkening (IPD) induced by the visible fraction of sunlight is not significantly different from that induced by the UV fraction. However, the persistent pigment darkening (PPD) induced by visible fraction of sunlight in significantly lower than that induced by the UV fraction. The dose responses of IPD induced by UV, visible light and total sunlight suggest that both UV and visible light interact with the same precursor although UV is 25 times more efficient in inducing pigmentation per J cm(-2) of irradiation compared to visible radiation. The measured diffused reflection spectra and decay kinetics of UV and visible radiation-induced pigmentation are very similar, indicating that the nature of the transient and persistent species involved in both the processes are also likely to be same.

The effects of topically applied glycolic acid and salicylic acid on ultraviolet radiation-induced erythema, DNA damage and sunburn cell formation in human skin.

PubMed

Kornhauser, Andrija; Wei, Rong-Rong; Yamaguchi, Yuji; Coelho, Sergio G; Kaidbey, Kays; Barton, Curtis; Takahashi, Kaoruko; Beer, Janusz Z; Miller, Sharon A; Hearing, Vincent J

2009-07-01

alpha-Hydroxy acids (alphaHAs) are reported to reduce signs of aging in the skin and are widely used cosmetic ingredients. Several studies suggest that alphaHA can increase the sensitivity of skin to ultraviolet radiation. More recently, beta-hydroxy acids (betaHAs), or combinations of alphaHA and betaHA have also been incorporated into antiaging skin care products. Concerns have also arisen about increased sensitivity to ultraviolet radiation following use of skin care products containing beta-HA. To determine whether topical treatment with glycolic acid, a representative alphaHA, or with salicylic acid, a betaHA, modifies the short-term effects of solar simulated radiation (SSR) in human skin. Fourteen subjects participated in this study. Three of the four test sites on the mid-back of each subject were treated daily Monday-Friday, for a total of 3.5 weeks, with glycolic acid (10%), salicylic acid (2%), or vehicle (control). The fourth site received no treatment. After the last treatment, each site was exposed to SSR, and shave biopsies from all four sites were obtained. The endpoints evaluated in this study were erythema (assessed visually and instrumentally), DNA damage and sunburn cell formation. Treatment with glycolic acid resulted in increased sensitivity of human skin to SSR, measured as an increase in erythema, DNA damage and sunburn cell formation. Salicylic acid did not produce significant changes in any of these biomarkers. Short-term topical application of glycolic acid in a cosmetic formulation increased the sensitivity of human skin to SSR, while a comparable treatment with salicylic acid did not.

Silibinin inhibits ultraviolet B radiation-induced DNA-damage and apoptosis by enhancing interleukin-12 expression in JB6 cells and SKH-1 hairless mouse skin.

PubMed

Narayanapillai, Sreekanth; Agarwal, Chapla; Deep, Gagan; Agarwal, Rajesh

2014-06-01

Recent studies have demonstrated silibinin efficacy against ultraviolet B (UVB)-induced skin carcinogenesis via different mechanisms in cell lines and animal models; however, its role in regulating interleukin-12 (IL-12), an immunomodulatory cytokine that reduces UVB-induced DNA damage and apoptosis, is not known. Here, we report that UVB irradiation causes caspase 3 and PARP cleavage and apoptosis, and addition of recombinant IL-12 or silibinin immediately after UVB significantly protects UVB-induced apoptosis in JB6 cells. IL-12 antibody-mediated blocking of IL-12 activity compromised the protective effects of both IL-12 and silibinin. Both silibinin and IL-12 also accelerated the repair of UVB-caused cyclobutane-pyrimidine dimers (CPDs) in JB6 cells. Additional studies confirmed that indeed silibinin causes a significant increase in IL-12 levels in UVB-irradiated JB6 cells as well as in mouse skin epidermis, and that similar to cell-culture findings, silibinin topical application immediately after UVB exposure causes a strong protection against UVB-induced TUNEL positive cells in epidermis possibly through a significantly accelerated repair of UVB-caused CPDs. Together, these findings for the first time provide an important insight regarding the pharmacological mechanism wherein silibinin induces endogenous IL-12 in its efficacy against UVB-caused skin damages. In view of the fact that an enhanced endogenous IL-12 level could effectively remove UVB-caused DNA damage and associated skin cancer, our findings suggest that the use of silibinin in UVB-damaged human skin would also be a practical and translational strategy to manage solar radiation-caused skin damages as well as skin cancer. © 2013 Wiley Periodicals, Inc.

Different susceptibility of cells of porcine skin and internal organs to ultraviolet A-induced breaking of nuclear DNA.

PubMed

Brozyna, Anna; Chwirot, Barbara W

2005-01-01

There is a continuously growing interest in medical applications of ultraviolet radiation (UV-A and long-wavelength UV-B) especially for laser surgery, phototherapy and photodiagnostics of human internal organs. UV-B and UV-A radiation is potentially mutagenic, however, there has been very little information published to date concerning the significance of possible deleterious action of such photons on cells of internal tissues. The aim of this study is to compare the sensitivities of skin cells to those of internal organs upon exposure to UV-A. To assess this sensitivity we have determined the UV-A dose-dependent frequency of nuclear DNA breaks detected with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) technique. The materials for the study were macroscopic samples of porcine skin, colon and esophagus. The UV-A dose ranged from 0.1 to 1000 mJ/cm2, which is similar to doses received by cells in regions examined with laser-induced fluorescence or by cells surrounding areas subject to a laser ablation. To reduce the influence of DNA repair processes the tissue samples were kept at a low temperature during the irradiation and were deep frozen immediately after completing the irradiation procedure. The cells of the internal organs are much more susceptible to UV-A-induced breaking of DNA than the skin cells. The percentage fractions and the spatial distributions of the damaged cells and the characteristics of the UV-A dose dependence seem to vary by type of internal organ.

Role of Ultraviolet Radiation in Papillomavirus-Induced Disease

PubMed Central

Uberoi, Aayushi; Yoshida, Satoshi; Frazer, Ian H.; Pitot, Henry C.; Lambert, Paul F.

2016-01-01

Human papillomaviruses are causally associated with 5% of human cancers. The recent discovery of a papillomavirus (MmuPV1) that infects laboratory mice provides unique opportunities to study the life cycle and pathogenesis of papillomaviruses in the context of a genetically manipulatable host organism. To date, MmuPV1-induced disease has been found largely to be restricted to severely immunodeficient strains of mice. In this study, we report that ultraviolet radiation (UVR), specifically UVB spectra, causes wild-type strains of mice to become highly susceptible to MmuPV1-induced disease. MmuPV1-infected mice treated with UVB develop warts that progress to squamous cell carcinoma. Our studies further indicate that UVB induces systemic immunosuppression in mice that correlates with susceptibility to MmuPV1-associated disease. These findings provide new insight into how MmuPV1 can be used to study the life cycle of papillomaviruses and their role in carcinogenesis, the role of host immunity in controlling papillomavirus-associated pathogenesis, and a basis for understanding in part the role of UVR in promoting HPV infection in humans. PMID:27244228

Role of Ultraviolet Radiation in Papillomavirus-Induced Disease.

PubMed

Uberoi, Aayushi; Yoshida, Satoshi; Frazer, Ian H; Pitot, Henry C; Lambert, Paul F

2016-05-01

Human papillomaviruses are causally associated with 5% of human cancers. The recent discovery of a papillomavirus (MmuPV1) that infects laboratory mice provides unique opportunities to study the life cycle and pathogenesis of papillomaviruses in the context of a genetically manipulatable host organism. To date, MmuPV1-induced disease has been found largely to be restricted to severely immunodeficient strains of mice. In this study, we report that ultraviolet radiation (UVR), specifically UVB spectra, causes wild-type strains of mice to become highly susceptible to MmuPV1-induced disease. MmuPV1-infected mice treated with UVB develop warts that progress to squamous cell carcinoma. Our studies further indicate that UVB induces systemic immunosuppression in mice that correlates with susceptibility to MmuPV1-associated disease. These findings provide new insight into how MmuPV1 can be used to study the life cycle of papillomaviruses and their role in carcinogenesis, the role of host immunity in controlling papillomavirus-associated pathogenesis, and a basis for understanding in part the role of UVR in promoting HPV infection in humans.

UV and ionizing radiations induced DNA damage, differences and similarities

NASA Astrophysics Data System (ADS)

Ravanat, Jean-Luc; Douki, Thierry

2016-11-01

Both UV and ionizing radiations damage DNA. Two main mechanisms, so-called direct and indirect pathways, are involved in the degradation of DNA induced by ionizing radiations. The direct effect of radiation corresponds to direct ionization of DNA (one electron ejection) whereas indirect effects are produced by reactive oxygen species generated through water radiolysis, including the highly reactive hydroxyl radicals, which damage DNA. UV (and visible) light damages DNA by again two distinct mechanisms. UVC and to a lesser extend UVB photons are directly absorbed by DNA bases, generating their excited states that are at the origin of the formation of pyrimidine dimers. UVA (and visible) light by interaction with endogenous or exogenous photosensitizers induce the formation of DNA damage through photosensitization reactions. The excited photosensitizer is able to induce either a one-electron oxidation of DNA (type I) or to produce singlet oxygen (type II) that reacts with DNA. In addition, through an energy transfer from the excited photosensitizer to DNA bases (sometime called type III mechanism) formation of pyrimidine dimers could be produced. Interestingly it has been shown recently that pyrimidine dimers are also produced by direct absorption of UVA light by DNA, even if absorption of DNA bases at these wavelengths is very low. It should be stressed that some excited photosensitizers (such as psoralens) could add directly to DNA bases to generate adducts. The review will described the differences and similarities in terms of damage formation (structure and mechanisms) between these two physical genotoxic agents.

DNA damage induced by the direct effect of radiation

NASA Astrophysics Data System (ADS)

Yokoya, A.; Shikazono, N.; Fujii, K.; Urushibara, A.; Akamatsu, K.; Watanabe, R.

2008-10-01

We have studied the nature of DNA damage induced by the direct effect of radiation. The yields of single- (SSB) and double-strand breaks (DSB), base lesions and clustered damage were measured using the agarose gel electrophoresis method after exposing to various kinds of radiations to a simple model DNA molecule, fully hydrated closed-circular plasmid DNA (pUC18). The yield of SSB does not show significant dependence on linear energy transfer (LET) values. On the other hand, the yields of base lesions revealed by enzymatic probes, endonuclease III (Nth) and formamidopyrimidine DNA glycosylase (Fpg), which excise base lesions and leave a nick at the damage site, strongly depend on LET values. Soft X-ray photon (150 kVp) irradiation gives a maximum yield of the base lesions detected by the enzymatic probes as SSB and clustered damage, which is composed of one base lesion and proximate other base lesions or SSBs. The clustered damage is visualized as an enzymatically induced DSB. The yields of the enzymatically additional damages strikingly decrease with increasing levels of LET. These results suggest that in higher LET regions, the repair enzymes used as probes are compromised because of the dense damage clustering. The studies using simple plasmid DNA as a irradiation sample, however, have a technical difficulty to detect multiple SSBs in a plasmid DNA. To detect the additional SSBs induced in opposite strand of the first SSB, we have also developed a novel technique of DNA-denaturation assay. This allows us to detect multiply induced SSBs in both strand of DNA, but not induced DSB.

Role of p53 in silibinin-mediated inhibition of ultraviolet B radiation-induced DNA damage, inflammation and skin carcinogenesis.

PubMed

Rigby, Cynthia M; Roy, Srirupa; Deep, Gagan; Guillermo-Lagae, Ruth; Jain, Anil K; Dhar, Deepanshi; Orlicky, David J; Agarwal, Chapla; Agarwal, Rajesh

2017-01-01

Non-melanoma skin cancers (NMSC) are a growing problem given that solar ultraviolet B (UVB) radiation exposure is increasing most likely due to depletion of the atmospheric ozone layer and lack of adequate sun protection. Better preventive methods are urgently required to reduce UV-caused photodamage and NMSC incidence. Earlier, we have reported that silibinin treatment activates p53 and reduces photodamage and NMSC, both in vitro and in vivo; but whether silibinin exerts its protective effects primarily through p53 remains unknown. To address this question, we generated p53 heterozygous (p53 +/- ) and p53 knockout (p53 -/- ) mice on SKH-1 hairless mouse background, and assessed silibinin efficacy in both short- and long-term UVB exposure experiments. In the chronic UVB-exposed skin tumorigenesis study, compared to p53 +/+ mice, p53 +/- mice developed skin tumors earlier and had higher tumor number, multiplicity and volume. Silibinin topical treatment significantly reduced the tumor number, multiplicity and volume in p53 +/+ mice but silibinin' protective efficacy was significantly compromised in p53 +/- mice. Additionally, silibinin treatment failed to inhibit precursor skin cancer lesions in p53 -/- mice but improved the survival of the mice. In short-term studies, silibinin application accelerated the removal of UVB-induced DNA damage in p53 +/+ mice while its efficacy was partially compromised in p53 -/- mice. Interestingly, silibinin treatment also inhibited the UVB-induced inflammatory markers in skin tissue. These results further confirmed that absence of the p53 allele predisposes mice to photodamage and photocarcinogenesis, and established that silibinin mediates its protection against UVB-induced photodamage, inflammation and photocarcinogenesis partly through p53 activation. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Role of p53 in silibinin-mediated inhibition of ultraviolet B radiation-induced DNA damage, inflammation and skin carcinogenesis

PubMed Central

Rigby, Cynthia M.; Roy, Srirupa; Deep, Gagan; Guillermo-Lagae, Ruth; Jain, Anil K.; Dhar, Deepanshi; Orlicky, David J.; Agarwal, Chapla; Agarwal, Rajesh

2017-01-01

Non-melanoma skin cancers (NMSC) are a growing problem given that solar ultraviolet B (UVB) radiation exposure is increasing most likely due to depletion of the atmospheric ozone layer and lack of adequate sun protection. Better preventive methods are urgently required to reduce UV-caused photodamage and NMSC incidence. Earlier, we have reported that silibinin treatment activates p53 and reduces photodamage and NMSC, both in vitro and in vivo; but whether silibinin exerts its protective effects primarily through p53 remains unknown. To address this question, we generated p53 heterozygous (p53+/−) and p53 knockout (p53−/−) mice on SKH-1 hairless mouse background, and assessed silibinin efficacy in both short- and long-term UVB exposure experiments. In the chronic UVB-exposed skin tumorigenesis study, compared to p53+/+ mice, p53+/− mice developed skin tumors earlier and had higher tumor number, multiplicity and volume. Silibinin topical treatment significantly reduced the tumor number, multiplicity and volume in p53+/+ mice but silibinin’ protective efficacy was significantly compromised in p53+/− mice. Additionally, silibinin treatment failed to inhibit precursor skin cancer lesions in p53−/− mice but improved the survival of the mice. In short-term studies, silibinin application accelerated the removal of UVB-induced DNA damage in p53+/+ mice while its efficacy was partially compromised in p53−/− mice. Interestingly, silibinin treatment also inhibited the UVB-induced inflammatory markers in skin tissue. These results further confirmed that absence of the p53 allele predisposes mice to photodamage and photocarcinogenesis, and established that silibinin mediates its protection against UVB-induced photodamage, inflammation and photocarcinogenesis partly through p53 activation. PMID:27729375

Radiation-induced transmethylation and transsulfuration in the system DNA-methionine

NASA Astrophysics Data System (ADS)

Köhnlein, W.; Merwitz, O.; Ohneseit, P.

Evidence is presented for the radiation-induced transmethylation and transsulfuration in a DNA-methionine model system. The extent of such alkylation of DNA is found to be comparable with that of alkylating agents. Therefore, both processes could be initial steps in radiation carcinogenesis. The protective effect of methionine on DNA strand breaks, due to scavenging of OH radicals, causes the formation of methyl and thiyl radicals.

Ultraviolet-radiation-induced methane emissions from meteorites and the Martian atmosphere.

PubMed

Keppler, Frank; Vigano, Ivan; McLeod, Andy; Ott, Ulrich; Früchtl, Marion; Röckmann, Thomas

2012-05-30

Almost a decade after methane was first reported in the atmosphere of Mars there is an intensive discussion about both the reliability of the observations--particularly the suggested seasonal and latitudinal variations--and the sources of methane on Mars. Given that the lifetime of methane in the Martian atmosphere is limited, a process on or below the planet's surface would need to be continuously producing methane. A biological source would provide support for the potential existence of life on Mars, whereas a chemical origin would imply that there are unexpected geological processes. Methane release from carbonaceous meteorites associated with ablation during atmospheric entry is considered negligible. Here we show that methane is produced in much larger quantities from the Murchison meteorite (a type CM2 carbonaceous chondrite) when exposed to ultraviolet radiation under conditions similar to those expected at the Martian surface. Meteorites containing several per cent of intact organic matter reach the Martian surface at high rates, and our experiments suggest that a significant fraction of the organic matter accessible to ultraviolet radiation is converted to methane. Ultraviolet-radiation-induced methane formation from meteorites could explain a substantial fraction of the most recently estimated atmospheric methane mixing ratios. Stable hydrogen isotope analysis unambiguously confirms that the methane released from Murchison is of extraterrestrial origin. The stable carbon isotope composition, in contrast, is similar to that of terrestrial microbial origin; hence, measurements of this signature in future Mars missions may not enable an unambiguous identification of biogenic methane.

Nuclear aggregates of polyamines in a radiation-induced DNA damage model.

PubMed

Iacomino, Giuseppe; Picariello, Gianluca; Stillitano, Ilaria; D'Agostino, Luciano

2014-02-01

Polyamines (PA) are believed to protect DNA minimizing the effect of radiation damage either by inducing DNA compaction and aggregation or acting as scavengers of free radicals. Using an in vitro pDNA double strand breakage assay based on gel electrophoretic mobility, we compared the protective capability of PA against γ-radiation with that of compounds generated by the supramolecular self-assembly of nuclear polyamines and phosphates, named Nuclear Aggregates of Polyamines (NAPs). Both unassembled PA and in vitro produced NAPs (ivNAPs) were ineffective in conferring pDNA protection at the sub-mM concentration. Single PA showed an appreciable protective effect only at high (mM) concentrations. However, concentrations of spermine (4+) within a critical range (0.481 mM) induced pDNA precipitation, an event that was not observed with NAPs-pDNA interaction. We conclude that the interaction of individual PA is ineffective to assure DNA protection, simultaneously preserving the flexibility and charge density of the double strand. Furthermore, data obtained by testing polyamine and ivNAPS with the current radiation-induced DNA damage model support the concept that PA-phosphate aggregates are the only forms through which PA interact with DNA. Copyright © 2013 Elsevier Ltd. All rights reserved.

Radiation-induced DNA-protein cross-links: Mechanisms and biological significance.

PubMed

Nakano, Toshiaki; Xu, Xu; Salem, Amir M H; Shoulkamy, Mahmoud I; Ide, Hiroshi

2017-06-01

Ionizing radiation produces various DNA lesions such as base damage, DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs), and DNA-protein cross-links (DPCs). Of these, the biological significance of DPCs remains elusive. In this article, we focus on radiation-induced DPCs and review the current understanding of their induction, properties, repair, and biological consequences. When cells are irradiated, the formation of base damage, SSBs, and DSBs are promoted in the presence of oxygen. Conversely, that of DPCs is promoted in the absence of oxygen, suggesting their importance in hypoxic cells, such as those present in tumors. DNA and protein radicals generated by hydroxyl radicals (i.e., indirect effect) are responsible for DPC formation. In addition, DPCs can also be formed from guanine radical cations generated by the direct effect. Actin, histones, and other proteins have been identified as cross-linked proteins. Also, covalent linkages between DNA and protein constituents such as thymine-lysine and guanine-lysine have been identified and their structures are proposed. In irradiated cells and tissues, DPCs are repaired in a biphasic manner, consisting of fast and slow components. The half-time for the fast component is 20min-2h and that for the slow component is 2-70h. Notably, radiation-induced DPCs are repaired more slowly than DSBs. Homologous recombination plays a pivotal role in the repair of radiation-induced DPCs as well as DSBs. Recently, a novel mechanism of DPC repair mediated by a DPC protease was reported, wherein the resulting DNA-peptide cross-links were bypassed by translesion synthesis. The replication and transcription of DPC-bearing reporter plasmids are inhibited in cells, suggesting that DPCs are potentially lethal lesions. However, whether DPCs are mutagenic and induce gross chromosomal alterations remains to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

Toll-Like Receptor-4 deficiency enhances repair of ultraviolet radiation induced cutaneous DNA damage by nucleotide excision repair mechanism

PubMed Central

Ahmad, Israr; Simanyi, Eva; Guroji, Purushotham; Tamimi, Iman A; delaRosa, Hillary J; Nagar, Anusuiya; Nagar, Priyamvada; Katiyar, Santosh K; Elmets, Craig A; Yusuf, Nabiha

2014-01-01

UVB-induced DNA damage plays a critical role in development of photoimmunosuppression. The purpose of this study was to determine whether repair of UVB-induced DNA damage is regulated by Toll-like receptor-4 (TLR4). When TLR4 gene knockout (TLR4-/-) and TLR4 competent (TLR4+/+) mice were subjected to 90 mJ/cm2 UVB radiation locally, DNA damage in the form of CPD, were repaired more efficiently in the skin and bone marrow dendritic cells (BMDC) of TLR4-/- mice in comparison to TLR4+/+ mice. Expression of DNA repair gene XPA (Xeroderma pigmentosum complementation group A) was significantly lower in skin and BMDC of TLR4+/+ mice than TLR4-/- mice after UVB exposure. When cytokine levels were compared in these strains after UVB exposure, BMDC from UV-irradiated TLR4-/- mice produced significantly more interleukin (IL)-12 and IL-23 cytokines (p<0.05) than BMDC from TLR4+/+ mice. Addition of anti-IL-12 and anti-IL-23 antibodies to BMDC of TLR4-/- mice (before UVB exposure) inhibited repair of CPD, with a concomitant decrease in XPA expression. Addition of TLR4 agonist to TLR4+/+ BMDC cultures decreased XPA expression and inhibited CPD repair. Thus, strategies to inhibit TLR4 may allow for immunopreventive and immunotherapeutic approaches for managing UVB-induced cutaneous DNA damage and skin cancer. PMID:24326454

Effects of early life exposure to ultraviolet C radiation on mitochondrial DNA content, transcription, ATP production, and oxygen consumption in developing Caenorhabditis elegans

PubMed Central

2013-01-01

Background Mitochondrial DNA (mtDNA) is present in multiple copies per cell and undergoes dramatic amplification during development. The impacts of mtDNA damage incurred early in development are not well understood, especially in the case of types of mtDNA damage that are irreparable, such as ultraviolet C radiation (UVC)-induced photodimers. Methods We exposed first larval stage nematodes to UVC using a protocol that results in accumulated mtDNA damage but permits nuclear DNA (nDNA) repair. We then measured the transcriptional response, as well as oxygen consumption, ATP levels, and mtDNA copy number through adulthood. Results Although the mtDNA damage persisted to the fourth larval stage, we observed only a relatively minor ~40% decrease in mtDNA copy number. Transcriptomic analysis suggested an inhibition of aerobic metabolism and developmental processes; mRNA levels for mtDNA-encoded genes were reduced ~50% at 3 hours post-treatment, but recovered and, in some cases, were upregulated at 24 and 48 hours post-exposure. The mtDNA polymerase γ was also induced ~8-fold at 48 hours post-exposure. Moreover, ATP levels and oxygen consumption were reduced in response to UVC exposure, with marked reductions of ~50% at the later larval stages. Conclusions These results support the hypothesis that early life exposure to mitochondrial genotoxicants could result in mitochondrial dysfunction at later stages of life, thereby highlighting the potential health hazards of time-delayed effects of these genotoxicants in the environment. PMID:23374645

Solar ultraviolet radiation induces biological alterations in human skin in vitro: relevance of a well-balanced UVA/UVB protection.

PubMed

Bernerd, Francoise; Marionnet, Claire; Duval, Christine

2012-06-01

Cutaneous damages such as sunburn, pigmentation, and photoaging are known to be induced by acute as well as repetitive sun exposure. Not only for basic research, but also for the design of the most efficient photoprotection, it is crucial to understand and identify the early biological events occurring after ultraviolet (UV) exposure. Reconstructed human skin models provide excellent and reliable in vitro tools to study the UV-induced alterations of the different skin cell types, keratinocytes, fibroblasts, and melanocytes in a dose- and time-dependent manner. Using different in vitro human skin models, the effects of UV light (UVB and UVA) were investigated. UVB-induced damages are essentially epidermal, with the typical sunburn cells and DNA lesions, whereas UVA radiation-induced damages are mostly located within the dermal compartment. Pigmentation can also be obtained after solar simulated radiation exposure of pigmented reconstructed skin model. Those models are also highly adequate to assess the potential of sunscreens to protect the skin from UV-associated damage, sunburn reaction, photoaging, and pigmentation. The results showed that an effective photoprotection is provided by broad-spectrum sunscreens with a potent absorption in both UVB and UVA ranges.

The Effects of Topically Applied Glycolic Acid and Salicylic Acid on Ultraviolet Radiation-Induced Erythema, DNA Damage and Sunburn Cell Formation in Human Skin

PubMed Central

Kornhauser, Andrija; Wei, Rong-Rong; Yamaguchi, Yuji; Coelho, Sergio G.; Kaidbey, Kays; Barton, Curtis; Takahashi, Kaoruko; Beer, Janusz Z.; Miller, Sharon A.; Hearing, Vincent J.

2009-01-01

Background α-Hydroxy acids (αHA) are reported to reduce signs of aging in the skin and are widely used cosmetic ingredients. Several studies suggest that αHA can increase the sensitivity of skin to ultraviolet radiation. More recently, β-hydroxy acids (βHA), or combinations of αHA and βHA have also been incorporated into antiaging skin care products. Concerns have also arisen about increased sensitivity to ultraviolet radiation following use of skin care products containing β-HA. Objective To determine whether topical treatment with glycolic acid, a representative αHA, or with salicylic acid, a βHA, modifies the short-term effects of solar simulated radiation (SSR) in human skin. Methods Fourteen subjects participated in this study. Three of the four test sites on the mid-back of each subject were treated daily Monday - Friday, for a total of 3.5 weeks, with glycolic acid (10%), salicylic acid (2%), or vehicle (control). The fourth site received no treatment. After the last treatment, each site was exposed to SSR, and shave biopsies from all 4 sites were obtained. The endpoints evaluated in this study were erythema (assessed visually and instrumentally), DNA damage and sunburn cell formation. Results Treatment with glycolic acid resulted in increased sensitivity of human skin to SSR, measured as an increase in erythema, DNA damage and sunburn cell formation. Salicylic acid did not produce significant changes in any of these biomarkers. Conclusions Short-term topical application of glycolic acid in a cosmetic formulation increased the sensitivity of human skin to SSR, while a comparable treatment with salicylic acid did not. PMID:19411163

Inhibition of seagrass photosynthesis by ultraviolet-B radiation.

PubMed

Trocine, R P; Rice, J D; Wells, G N

1981-07-01

Effects of ultraviolet-B radiation on the photosynthesis of seagrasses (Halophila engelmanni Aschers, Halodule wrightii Aschers, and Syringodium filiforme Kütz) were examined. The intrinsic tolerance of each seagrass to ultraviolet-B, the presence and effectiveness of photorepair mechanisms to ultraviolet-B-induced photosynthetic inhibition, and the role of epiphytic growth as a shield from ultraviolet-B were investigated.Halodule was found to possess the greatest photosynthetic tolerance for ultraviolet-B. Photosynthesis in Syringodium was slightly more sensitive to ultraviolet-B while Halophila showed relatively little photosynthetic tolerance. Evidence for a photorepair mechanism was found only in Halodule. This mechanism effectively attenuated photosynthetic inhibition induced by ultraviolet-B dose rates and dosages in excess of natural conditions. Syringodium appeared to rely primarily on a thick epidermal cell layer to reduce photosynthetic damage. Halophila seemed to have no morphological or photorepair capabilities to deal with ultraviolet-B. This species appeared to rely on epiphytic and detrital shielding and the shade provided by other seagrasses to reduce ultraviolet-B irradiation to tolerable levels. The presence of epiphytes on leaf surfaces was found to reduce the extent of photosynthetic inhibition from ultraviolet-B exposure in all species.Observations obtained in this study seem to suggest the possibility of anthocyanin and/or other flavonoid synthesis as an adaptation to long term ultraviolet-B irradiation by these species. In addition, Halophila appears to obtain an increased photosynthetic tolerance to ultraviolet-B as an indirect benefit of chloroplast clumping to avoid photo-oxidation by intense levels of photosynthetically active radiation.

Parkin regulates translesion DNA synthesis in response to UV radiation.

PubMed

Zhu, Xuefei; Ma, Xiaolu; Tu, Yingfeng; Huang, Min; Liu, Hongmei; Wang, Fengli; Gong, Juanjuan; Wang, Jiuqiang; Li, Xiaoling; Chen, Qian; Shen, Hongyan; Zhu, Shu; Wang, Yun; Liu, Yang; Guo, Caixia; Tang, Tie-Shan

2017-05-30

Deficiency of Parkin is a major cause of early-onset Parkinson's disease (PD). Notably, PD patients also exhibit a significantly higher risk in melanoma and other skin tumors, while the mechanism remains largely unknown. In this study, we show that depletion of Parkin causes compromised cell viability and genome stability after ultraviolet (UV) radiation. We demonstrate that Parkin promotes efficient Rad18-dependent proliferating cell nuclear antigen (PCNA) monoubiquitination by facilitating the formation of Replication protein A (RPA)-coated ssDNA upon UV radiation. Furthermore, Parkin is found to physically interact with NBS1 (Nijmegen breakage syndrome 1), and to be required for optimal recruitment of NBS1 and DNA polymerase eta (Polη) to UV-induced damage sites. Consequently, depletion of Parkin leads to increased UV-induced mutagenesis. These findings unveil an important role of Parkin in protecting genome stability through positively regulating translesion DNA synthesis (TLS) upon UV damage, providing a novel mechanistic link between Parkin deficiency and predisposition to skin cancers in PD patients.

Human Retinal Transmitochondrial Cybrids with J or H mtDNA Haplogroups Respond Differently to Ultraviolet Radiation: Implications for Retinal Diseases

PubMed Central

Malik, Deepika; Hsu, Tiffany; Falatoonzadeh, Payam; Cáceres-del-Carpio, Javier; Tarek, Mohamed; Chwa, Marilyn; Atilano, Shari R.; Ramirez, Claudio; Nesburn, Anthony B.; Boyer, David S.; Kuppermann, Baruch D.; Jazwinski, S. Michal; Miceli, Michael V.; Wallace, Douglas C.; Udar, Nitin; Kenney, M. Cristina

2014-01-01

Background It has been recognized that cells do not respond equally to ultraviolet (UV) radiation but it is not clear whether this is due to genetic, biochemical or structural differences of the cells. We have a novel cybrid (cytoplasmic hybrids) model that allows us to analyze the contribution of mitochondrial DNA (mtDNA) to cellular response after exposure to sub-lethal dose of UV. mtDNA can be classified into haplogroups as defined by accumulations of specific single nucleotide polymorphisms (SNPs). Recent studies have shown that J haplogroup is high risk for age-related macular degeneration while the H haplogroup is protective. This study investigates gene expression responses in J cybrids versus H cybrids after exposure to sub-lethal doses of UV-radiation. Methodology/Principal Findings Cybrids were created by fusing platelets isolated from subjects with either H (n = 3) or J (n = 3) haplogroups with mitochondria-free (Rho0) ARPE-19 cells. The H and J cybrids were cultured for 24 hours, treated with 10 mJ of UV-radiation and cultured for an additional 120 hours. Untreated and treated cybrids were analyzed for growth rates and gene expression profiles. The UV-treated and untreated J cybrids had higher growth rates compared to H cybrids. Before treatment, J cybrids showed lower expression levels for CFH, CD55, IL-33, TGF-A, EFEMP-1, RARA, BCL2L13 and BBC3. At 120 hours after UV-treatment, the J cybrids had decreased CFH, RARA and BBC3 levels but increased CD55, IL-33 and EFEMP-1 compared to UV-treated H cybrids. Conclusion/Significance In cells with identical nuclei, the cellular response to sub-lethal UV-radiation is mediated in part by the mtDNA haplogroup. This supports the hypothesis that differences in growth rates and expression levels of complement, inflammation and apoptosis genes may result from population-specific, hereditary SNP variations in mtDNA. Therefore, when analyzing UV-induced damage in tissues, the mtDNA haplogroup background may be

DNA damage in cells exhibiting radiation-induced genomic instability

DOE PAGES

Keszenman, Deborah J.; Kolodiuk, Lucia; Baulch, Janet E.

2015-02-22

Cells exhibiting radiation induced genomic instability exhibit varied spectra of genetic and chromosomal aberrations. Even so, oxidative stress remains a common theme in the initiation and/or perpetuation of this phenomenon. Isolated oxidatively modified bases, abasic sites, DNA single strand breaks and clustered DNA damage are induced in normal mammalian cultured cells and tissues due to endogenous reactive oxygen species generated during normal cellular metabolism in an aerobic environment. While sparse DNA damage may be easily repaired, clustered DNA damage may lead to persistent cytotoxic or mutagenic events that can lead to genomic instability. In this study, we tested the hypothesismore » that DNA damage signatures characterised by altered levels of endogenous, potentially mutagenic, types of DNA damage and chromosomal breakage are related to radiation-induced genomic instability and persistent oxidative stress phenotypes observed in the chromosomally unstable progeny of irradiated cells. The measurement of oxypurine, oxypyrimidine and abasic site endogenous DNA damage showed differences in non-double-strand breaks (DSB) clusters among the three of the four unstable clones evaluated as compared to genomically stable clones and the parental cell line. These three unstable clones also had increased levels of DSB clusters. The results of this study demonstrate that each unstable cell line has a unique spectrum of persistent damage and lead us to speculate that alterations in DNA damage signaling and repair may be related to the perpetuation of genomic instability.« less

Is UV-induced DNA damage greater at higher elevation?

PubMed

Wang, Qing-Wei; Hidema, Jun; Hikosaka, Kouki

2014-05-01

• Although ultraviolet radiation (UV) is known to have negative effects on plant growth, there has been no direct evidence that plants growing at higher elevations are more severely affected by ultraviolet-B (UV-B) radiation, which is known to increase with elevation. We examined damage to DNA, a primary target of UV-B, in the widespread species Polygonum sachalinense (Fallopia sachalinensis) and Plantago asiatica at two elevations.• We sampled leaves of both species at 300 and 1700 m above sea level every 2 h for 11 d across the growing season and determined the level of cyclobutane pyrimidine dimer (CPD), a major product of UV damage to DNA.• The CPD level was significantly influenced by the time of day, date, elevation, and their interactions in both species. The CPD level tended to be higher at noon or on sunny days. DNA damage was more severe at 1700 m than at 300 m: on average, 8.7% greater at high elevation in P. asiatica and 7.8% greater in P. sachalinense Stepwise multiple regression analysis indicated that the CPD level was explained mainly by UV-B and had no significant relationship with other environmental factors such as temperature and photosynthetically active radiation.• UV-induced DNA damage in plants is greater at higher elevations. © 2014 Botanical Society of America, Inc.

Solar simulated ultraviolet radiation damages murine neonatal skin and alters Langerhans cell development, but does not induce inflammation.

PubMed

McGee, Heather M; Dharmadasa, Thanuja; Woods, Gregory M

2009-06-01

Development of melanoma has been linked to excessive childhood exposure to sunlight. As neonates have a relatively underdeveloped immune system, it is likely that the immune system reacts differently to the exposure, leading to alterations in this development. This study was designed to assess changes in development of the skin immune system following neonatal irradiation. Ultraviolet radiation exposure led to relative depletion of Langerhans cells, however this was not due to migration or cell death, but rather restriction of Langerhans cells populating the epidermis. During this time, there was evidence of cellular damage, however there was no induction of an inflammatory response. It therefore appears that neonatal exposure to ultraviolet radiation leads to a skew towards a tolerogenic immune response, which may lead to a reduced ability to respond to ultraviolet radiation-induced tumours.

An ultraviolet simulator for the incident Martian surface radiation and its applications

NASA Astrophysics Data System (ADS)

Kolb, C.; Abart, R.; Bérces, A.; Garry, J. R. C.; Hansen, A. A.; Hohenau, W.; Kargl, G.; Lammer, H.; Patel, M. R.; Rettberg, P.; Stan-Lotter, H.

2005-10-01

Ultraviolet (UV) radiation can act on putative organic/biological matter at the Martian surface in several ways. Only absorbed, but not transmitted or reflected, radiation energy can be photo-chemically effective. The most important biological UV effects are due to photochemical reactions in nucleic acids, DNA or RNA, which constitute the genetic material of all cellular organisms and viruses. Protein or lipid effects generally play a minor role, but they are also relevant in some cases. UV radiation can induce wavelengths-specific types of DNA damage. At the same time it can also induce the photo-reversion reaction of a UV induced DNA photoproduct of nucleic acid bases, the pyrimidine dimers. Intense UVB and UVC radiation, experienced on early Earth and present-day Mars, has been revealed to be harmful to all organisms, including extremophile bacteria and spores. Moreover, the formation of oxidants, catalytically produced in the Martian environment through UV irradiation, may be responsible for the destruction of organic matter on Mars. Following this, more laboratory simulations are vital in order to investigate and understand UV effects on organic matter in the case of Mars. We have designed a radiation apparatus that simulates the anticipated Martian UV surface spectrum between 200 and 400 nm (UVC UVA). The system comprises a UV enhanced xenon arc lamp, special filter-sets and mirrors to simulate the effects of the Martian atmospheric column and dust loading. We describe the technical setup and performance of the system and discuss its uses for different applications. The design is focused on portability, therefore, the Mars-UV simulator represents a device for several different Mars simulation facilities with specific emphasis on Mars research topics.

EFFECT OF ARSENICALS ON ULTRAVIOLET-RADIATION-INDUCED GROWTH ARREST AND RELATED SIGNALING EVENTS IN HUMAN KERATINOCYTES

EPA Science Inventory

The molecular mechanisms mediating arsenic-induced carcinogenesis are not well understood. The role of confounding factors such as ultraviolet radiation (UV), add another level of complexity to the study of arsenic carcinogenesis and the cancer risk assessment to humans. We hypot...

Production of thymine glycols in DNA by radiation and chemical carcinogens as detected by a monoclonal antibody.

PubMed Central

Leadon, S. A.

1987-01-01

In order to understand the role in carcinogenesis of damage indirectly induced by chemical carcinogens, it is important to identify the primary DNA lesions. We have measured the formation and repair of one type of DNA modification, 5,6-dihydroxydihydrothymine (thymine glycol), following exposure of cultured human cells to the carcinogens N-hydroxy-2-naphthylamine or benzo(a)pyrene. The efficiency of production of thymine glycols in DNA by these carcinogens was compared to that by ionizing radiation and ultraviolet light. Thymine glycols were detected using a monoclonal antibody against this product in a sensitive immunoassay. We found that thymine glycols were produced in DNA in a dose dependent manner after exposure to the carcinogens and that their production was reduced if either catalase or superoxide dismutase or both were present at the time of treatment. The efficiency of thymine glycol production following exposure to the chemical carcinogens was greater than that following equi-toxic doses of radiation. Thymine glycols were efficiently removed from the DNA of human cells following treatment with either the chemical carcinogens, ionizing radiation or ultraviolet light. PMID:3477281

Inhibition of Seagrass Photosynthesis by Ultraviolet-B Radiation 1

PubMed Central

Trocine, Robert P.; Rice, John D.; Wells, Gary N.

1981-01-01

Effects of ultraviolet-B radiation on the photosynthesis of seagrasses (Halophila engelmanni Aschers, Halodule wrightii Aschers, and Syringodium filiforme Kütz) were examined. The intrinsic tolerance of each seagrass to ultraviolet-B, the presence and effectiveness of photorepair mechanisms to ultraviolet-B-induced photosynthetic inhibition, and the role of epiphytic growth as a shield from ultraviolet-B were investigated. Halodule was found to possess the greatest photosynthetic tolerance for ultraviolet-B. Photosynthesis in Syringodium was slightly more sensitive to ultraviolet-B while Halophila showed relatively little photosynthetic tolerance. Evidence for a photorepair mechanism was found only in Halodule. This mechanism effectively attenuated photosynthetic inhibition induced by ultraviolet-B dose rates and dosages in excess of natural conditions. Syringodium appeared to rely primarily on a thick epidermal cell layer to reduce photosynthetic damage. Halophila seemed to have no morphological or photorepair capabilities to deal with ultraviolet-B. This species appeared to rely on epiphytic and detrital shielding and the shade provided by other seagrasses to reduce ultraviolet-B irradiation to tolerable levels. The presence of epiphytes on leaf surfaces was found to reduce the extent of photosynthetic inhibition from ultraviolet-B exposure in all species. Observations obtained in this study seem to suggest the possibility of anthocyanin and/or other flavonoid synthesis as an adaptation to long term ultraviolet-B irradiation by these species. In addition, Halophila appears to obtain an increased photosynthetic tolerance to ultraviolet-B as an indirect benefit of chloroplast clumping to avoid photo-oxidation by intense levels of photosynthetically active radiation. Images PMID:16661893

Silibinin enhances the repair of ultraviolet B-induced DNA damage by activating p53-dependent nucleotide excision repair mechanism in human dermal fibroblasts

PubMed Central

Guillermo-Lagae, Ruth; Deep, Gagan; Ting, Harold; Agarwal, Chapla; Agarwal, Rajesh

2015-01-01

Ultraviolet radiation B (UVB) is the main cause of DNA damage in epidermal cells; and if not repaired, this DNA damage leads to skin cancer. In earlier studies, we have reported that natural flavonolignan silibinin exerts strong chemopreventive efficacy against UVB-induced skin damage and carcinogenesis; however mechanistic studies are still being actively pursued. Here, we investigated the role of nucleotide excision repair (NER) pathway in silibinin's efficacy to repair UVB-induced DNA damage. Normal human dermal fibroblasts (NHDFs) were exposed to UVB (1 mJ/cm2) with pre- or post- silibinin (100 μM) treatment, and cyclobutane pyrimidine dimers (CPDs) formation/repair was measured. Results showed that post-UVB silibinin treatment accelerates DNA repair via activating the NER pathway including the expression of XPA (xeroderma pigmentosum complementation group A), XPB, XPC, and XPG. In UVB exposed fibroblasts, silibinin treatment also increased p53 and GADD45α expression; the key regulators of the NER pathway and DNA repair. Consistently, post-UVB silibinin treatment increased the mRNA transcripts of XPA and GADD45α. Importantly, silibinin showed no effect on UVB-induced DNA damage repair in XPA- and XPB-deficient human dermal fibroblasts suggesting their key role in silibinin-mediated DNA damage repair. Moreover, in the presence of pifithrin-α, an inhibitor of p53, the DNA repair efficacy of silibinin was compromised associated with a reduction in XPA and GADD45α transcripts. Together, these findings suggest that silibinin's efficacy against UVB-induced photodamage is primarily by inhibiting NER and p53; and these findings further support silibinin's usage as a potential inexpensive, effective, and non-toxic agent for skin cancer chemoprevention. PMID:26447614

Silibinin enhances the repair of ultraviolet B-induced DNA damage by activating p53-dependent nucleotide excision repair mechanism in human dermal fibroblasts.

PubMed

Guillermo-Lagae, Ruth; Deep, Gagan; Ting, Harold; Agarwal, Chapla; Agarwal, Rajesh

2015-11-24

Ultraviolet radiation B (UVB) is the main cause of DNA damage in epidermal cells; and if not repaired, this DNA damage leads to skin cancer. In earlier studies, we have reported that natural flavonolignan silibinin exerts strong chemopreventive efficacy against UVB-induced skin damage and carcinogenesis; however mechanistic studies are still being actively pursued. Here, we investigated the role of nucleotide excision repair (NER) pathway in silibinin's efficacy to repair UVB-induced DNA damage. Normal human dermal fibroblasts (NHDFs) were exposed to UVB (1 mJ/cm2) with pre- or post- silibinin (100 μM) treatment, and cyclobutane pyrimidine dimers (CPDs) formation/repair was measured. Results showed that post-UVB silibinin treatment accelerates DNA repair via activating the NER pathway including the expression of XPA (xeroderma pigmentosum complementation group A), XPB, XPC, and XPG. In UVB exposed fibroblasts, silibinin treatment also increased p53 and GADD45α expression; the key regulators of the NER pathway and DNA repair. Consistently, post-UVB silibinin treatment increased the mRNA transcripts of XPA and GADD45α. Importantly, silibinin showed no effect on UVB-induced DNA damage repair in XPA- and XPB-deficient human dermal fibroblasts suggesting their key role in silibinin-mediated DNA damage repair. Moreover, in the presence of pifithrin-α, an inhibitor of p53, the DNA repair efficacy of silibinin was compromised associated with a reduction in XPA and GADD45α transcripts. Together, these findings suggest that silibinin's efficacy against UVB-induced photodamage is primarily by inhibiting NER and p53; and these findings further support silibinin's usage as a potential inexpensive, effective, and non-toxic agent for skin cancer chemoprevention.

Inhibition of seagrass photosynthesis by ultraviolet-B radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trocine, R.P.; Rice, J.D.; Wells, G.N.

1981-07-01

Effects of ultraviolet-B radiation on the photosynthesis of seagrasses (Halophila engelmanni Aschers, Halodule wrightii Aschers, and Syringodium filiforme (Kuetz) were examined. The intrinsic tolerance of each seagrass to ultraviolet-B, the presence and effectiveness of photorepair mechanisms to ultraviolet-B-induced photosynthetic inhibition, and the role of epiphytic growth as a shield from ultraviolet-B were investigated. Halodule was found to possess the greatest photosynthetic tolerance for ultraviolet-B. Photosynthesis in Syringodium was slightly more sensitive to ultraviolet-B while Halophila showed relatively little photosynthetic tolerance. Evidence for a photorepair mechanism was found only in Halodule. Syringodium appeared to rely primarily on a thick epidermal cellmore » layer to reduce photosynthetic damage. Halophila seemed to have no morphological or photorepair capabilities to deal with ultraviolet-B. This species appeared to rely on epiphytic and detrital shielding and the shade provided by other seagrasses to reduce ultraviolet-B irradiation to tolerable levels. The presence of epiphytes on leaf surfaces was found to reduce the extent of photosynthetic inhibition from ultraviolet-B exposure in all species. Halophila appears to obtain an increased photosynthetic tolerance to ultraviolet-B as an indirect benefit of chloroplast clumping to avoid photo-oxidation by intense levels of photosynthetically active radiation.« less

Photoprotection beyond ultraviolet radiation--effective sun protection has to include protection against infrared A radiation-induced skin damage.

PubMed

Schroeder, P; Calles, C; Benesova, T; Macaluso, F; Krutmann, J

2010-01-01

Solar radiation is well known to damage human skin, for example by causing premature skin ageing (i.e. photoageing). We have recently learned that this damage does not result from ultraviolet (UV) radiation alone, but also from longer wavelengths, in particular near-infrared radiation (IRA radiation, 760-1,440 nm). IRA radiation accounts for more than one third of the solar energy that reaches human skin. While infrared radiation of longer wavelengths (IRB and IRC) does not penetrate deeply into the skin, more than 65% of the shorter wavelength (IRA) reaches the dermis. IRA radiation has been demonstrated to alter the collagen equilibrium of the dermal extracellular matrix in at least two ways: (a) by leading to an increased expression of the collagen-degrading enzyme matrix metalloproteinase 1, and (b) by decreasing the de novo synthesis of the collagen itself. IRA radiation exposure therefore induces similar biological effects to UV radiation, but the underlying mechanisms are substantially different, specifically, the cellular response to IRA irradiation involves the mitochondrial electron transport chain. Effective sun protection requires specific strategies to prevent IRA radiation-induced skin damage. 2010 S. Karger AG, Basel.

Effects of ultraviolet radiation, visible light, and infrared radiation on erythema and pigmentation: a review.

PubMed

Sklar, Lindsay R; Almutawa, Fahad; Lim, Henry W; Hamzavi, Iltefat

2013-01-01

The effects of ultraviolet radiation, visible light, and infrared radiation on cutaneous erythema, immediate pigment darkening, persistent pigment darkening, and delayed tanning are affected by a variety of factors. Some of these factors include the depth of cutaneous penetration of the specific wavelength, the individual skin type, and the absorption spectra of the different chromophores in the skin. UVB is an effective spectrum to induce erythema, which is followed by delayed tanning. UVA induces immediate pigment darkening, persistent pigment darkening, and delayed tanning. At high doses, UVA (primarily UVA2) can also induce erythema in individuals with skin types I-II. Visible light has been shown to induce erythema and a tanning response in dark skin, but not in fair skinned individuals. Infrared radiation produces erythema, which is probably a thermal effect. In this article we reviewed the available literature on the effects of ultraviolet radiation, visible light, and infrared radiation on the skin in regards to erythema and pigmentation. Much remains to be learned on the cutaneous effects of visible light and infrared radiation.

Resistance of a lizard (the green anole, Anolis carolinensis; Polychridae) to ultraviolet radiation-induced immunosuppression

USGS Publications Warehouse

Cope, R.B.; Fabacher, D.L.; Lieske, C.; Miller, C.A.

2001-01-01

The green anole (Anolis carolinensis) is the most northerly distributed of its Neotropical genus. This lizard avoids a winter hibernation phase by the use of sun basking behaviors. Inevitably, this species is exposed to high doses of ambient solar ultraviolet radiation (UVR). Increases in terrestrial ultraviolet-B (UV-B) radiation secondary to stratospheric ozone depletion and habitat perturbation potentially place this species at risk of UVR-induced immunosuppression. Daily exposure to subinflammatory UVR (8 kJ/m2/day UV-B, 85 kJ/m2/day ultraviolet A [UV-A]), 6 days per week for 4 weeks (total cumulative doses of 192 kJ/m2 UV-B, 2.04 × 103 kJ/m2 UV-A) did not suppress the anole's acute or delayed type hypersensitivity (DTH) response to horseshoe crab hemocyanin. In comparison with the available literature UV-B doses as low as 0.1 and 15.9 kJ/m2 induced suppression of DTH responses in mice and humans, respectively. Exposure of anoles to UVR did not result in the inhibition of ex vivo splenocyte phagocytosis of fluorescein labeled Escherichia coli or ex vivo splenocyte nitric oxide production. Doses of UV-B ranging from 0.35 to 45 kJ/m2 have been reported to suppress murine splenic/peritoneal macrophage phagocytosis and nitric oxide production. These preliminary studies demonstrate the resistance of green anoles to UVR-induced immunosuppression. Methanol extracts of anole skin contained two peaks in the ultraviolet wavelength range that could be indicative of photoprotective substances. However, the resistance of green anoles to UVR is probably not completely attributable to absorption by UVR photoprotective substances in the skin but more likely results from a combination of other factors including absorption by the cutis and absorption and reflectance by various components of the dermis.

UVA photoactivation of DNA containing halogenated thiopyrimidines induces cytotoxic DNA lesions

PubMed Central

Brem, Reto; Zhang, Xiaohui; Xu, Yao-Zhong; Karran, Peter

2015-01-01

Photochemotherapy, the combination of a photosensitiser and ultraviolet (UV) or visible light, is an effective treatment for skin conditions including cancer. The high mutagenicity and non-selectivity of photochemotherapy regimes warrants the development of alternative approaches. We demonstrate that the thiopyrimidine nucleosides 5-bromo-4-thiodeoxyuridine (SBrdU) and 5-iodo-4-thiodeoxyuridine (SIdU) are incorporated into the DNA of cultured human and mouse cells where they synergistically sensitise killing by low doses of UVA radiation. The DNA halothiopyrimidine/UVA combinations induce DNA interstrand crosslinks, DNA-protein crosslinks, DNA strand breaks, nucleobase damage and lesions that resemble UV-induced pyrimidine(6-4)pyrimidone photoproducts. These are potentially lethal DNA lesions and cells defective in their repair are hypersensitive to killing by SBrdU/UVA and SIdU/UVA. DNA SIdU and SBrdU generate lethal DNA photodamage by partially distinct mechanisms that reflect the different photolabilities of their C–I and C–Br bonds. Although singlet oxygen is involved in photolesion formation, DNA SBrdU and SIdU photoactivation does not detectably increase DNA 8-oxoguanine levels. The absence of significant collateral damage to normal guanine suggests that UVA activation of DNA SIdU or SBrdU might offer a strategy to target hyperproliferative skin conditions that avoids the extensive formation of a known mutagenic DNA lesion. PMID:25747491

GSK126 (EZH2 inhibitor) interferes with ultraviolet A radiation-induced photoaging of human skin fibroblast cells

PubMed Central

Qin, Haiyan; Zhang, Guang; Zhang, Lianbo

2018-01-01

Polycomb group genes (PcG) encode chromatin modification proteins that are involved in the epigenetic regulation of cell differentiation, proliferation and the aging processes. The key subunit of the PcG complex, enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), has a central role in a variety of mechanisms, such as the formation of chromatin structure, gene expression regulation and DNA damage. In the present study, ultraviolet A (UVA) was used to radiate human dermal fibroblasts in order to construct a photo-aged cell model. Subsequently, the cell viability assay, Hoechst staining, apoptosis detection using flow cytometry, senescence-associated β-galactosidase (SA-β-gal) staining and erythrocyte exclusion experiments were performed. GSK126, a histone methylation enzyme inhibitor of EZH2, was used as an experimental factor. Results suggested that GSK126 downregulated the mRNA expression levels of EZH2 and upregulated the mRNA expression levels of BMI-1. Notably, GSK126 affected the transcription of various photoaging-related genes and thus protected against photoaging induced by UVA radiation. PMID:29545866

Parkin regulates translesion DNA synthesis in response to UV radiation

PubMed Central

Huang, Min; Liu, Hongmei; Wang, Fengli; Gong, Juanjuan; Wang, Jiuqiang; Li, Xiaoling; Chen, Qian; Shen, Hongyan; Zhu, Shu; Wang, Yun; Liu, Yang; Guo, Caixia; Tang, Tie-Shan

2017-01-01

Deficiency of Parkin is a major cause of early-onset Parkinson's disease (PD). Notably, PD patients also exhibit a significantly higher risk in melanoma and other skin tumors, while the mechanism remains largely unknown. In this study, we show that depletion of Parkin causes compromised cell viability and genome stability after ultraviolet (UV) radiation. We demonstrate that Parkin promotes efficient Rad18-dependent proliferating cell nuclear antigen (PCNA) monoubiquitination by facilitating the formation of Replication protein A (RPA)-coated ssDNA upon UV radiation. Furthermore, Parkin is found to physically interact with NBS1 (Nijmegen breakage syndrome 1), and to be required for optimal recruitment of NBS1 and DNA polymerase eta (Polη) to UV-induced damage sites. Consequently, depletion of Parkin leads to increased UV-induced mutagenesis. These findings unveil an important role of Parkin in protecting genome stability through positively regulating translesion DNA synthesis (TLS) upon UV damage, providing a novel mechanistic link between Parkin deficiency and predisposition to skin cancers in PD patients. PMID:28430587

Whales Use Distinct Strategies to Counteract Solar Ultraviolet Radiation

PubMed Central

Martinez-Levasseur, Laura M.; Birch-Machin, Mark A.; Bowman, Amy; Gendron, Diane; Weatherhead, Elizabeth; Knell, Robert J.; Acevedo-Whitehouse, Karina

2013-01-01

A current threat to the marine ecosystem is the high level of solar ultraviolet radiation (UV). Large whales have recently been shown to suffer sun-induced skin damage from continuous UV exposure. Genotoxic consequences of such exposure remain unknown for these long-lived marine species, as does their capacity to counteract UV-induced insults. We show that UV exposure induces mitochondrial DNA damage in the skin of seasonally sympatric fin, sperm, and blue whales and that this damage accumulates with age. However, counteractive molecular mechanisms are markedly different between species. For example, sperm whales, a species that remains for long periods at the sea surface, activate genotoxic stress pathways in response to UV exposure whereas the paler blue whale relies on increased pigmentation as the season progresses. Our study also shows that whales can modulate their responses to fluctuating levels of UV, and that different evolutionary constraints may have shaped their response strategies. PMID:23989080

An Overview of Ultraviolet B Radiation-Induced Skin Cancer Chemoprevention by Silibinin.

PubMed

Kumar, Rahul; Deep, Gagan; Agarwal, Rajesh

2015-06-01

Skin cancer incidences are rising worldwide, and one of the major causative factors is excessive exposure to solar ultraviolet radiation (UVR). Annually, ~5 million skin cancer patients are treated in United States, mostly with nonmelanoma skin cancer (NMSC), which is also frequent in other Western countries. As sunscreens do not provide adequate protection against deleterious effects of UVR, additional and alternative chemoprevention strategies are urgently needed to reduce skin cancer burden. Over the last couple of decades, extensive research has been conducted to understand the molecular basis of skin carcinogenesis, and to identifying novel agents which could be useful in the chemoprevention of skin cancer. In this regard, several natural non-toxic compounds have shown promising efficacy in preventing skin carcinogenesis at initiation, promotion and progression stages, and are considered important in better management of skin cancer. Consistent with this, we and others have studied and established the notable efficacy of natural flavonolignan silibinin against UVB-induced skin carcinogenesis. Extensive pre-clinical animal and cell culture studies report strong anti-inflammatory, anti-oxidant, DNA damage repair, immune-modulatory and anti-proliferative properties of silibinin. Molecular studies have identified that silibinin targets pleotropic signaling pathways including mitogenic, cell cycle, apoptosis, autophagy, p53, NF-κB, etc. Overall, the skin cancer chemopreventive potential of silibinin is well supported by comprehensive mechanistic studies, suggesting its greater use against UV-induced cellular damages and photocarcinogenesis.

An Overview of Ultraviolet B Radiation-Induced Skin Cancer Chemoprevention by Silibinin

PubMed Central

Kumar, Rahul; Deep, Gagan; Agarwal, Rajesh

2015-01-01

Skin cancer incidences are rising worldwide, and one of the major causative factors is excessive exposure to solar ultraviolet radiation (UVR). Annually, ~5 million skin cancer patients are treated in United States, mostly with nonmelanoma skin cancer (NMSC), which is also frequent in other Western countries. As sunscreens do not provide adequate protection against deleterious effects of UVR, additional and alternative chemoprevention strategies are urgently needed to reduce skin cancer burden. Over the last couple of decades, extensive research has been conducted to understand the molecular basis of skin carcinogenesis, and to identifying novel agents which could be useful in the chemoprevention of skin cancer. In this regard, several natural non-toxic compounds have shown promising efficacy in preventing skin carcinogenesis at initiation, promotion and progression stages, and are considered important in better management of skin cancer. Consistent with this, we and others have studied and established the notable efficacy of natural flavonolignan silibinin against UVB-induced skin carcinogenesis. Extensive pre-clinical animal and cell culture studies report strong anti-inflammatory, anti-oxidant, DNA damage repair, immune-modulatory and anti-proliferative properties of silibinin. Molecular studies have identified that silibinin targets pleotropic signaling pathways including mitogenic, cell cycle, apoptosis, autophagy, p53, NF-κB, etc. Overall, the skin cancer chemopreventive potential of silibinin is well supported by comprehensive mechanistic studies, suggesting its greater use against UV-induced cellular damages and photocarcinogenesis. PMID:26097804

DETECTION OF LOW DOSE RADIATION-AND CHEMICALLY-INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENTIAL FLUORESCENCE ASSAYS

EPA Science Inventory

Rapid, sensitive and simple assays for radiation- and chemically-induced DNA damage can be of significant benefit to a number of fields including radiation biology, clinical research, and environmental monitoring. Although temperature-induced DNA strand separation has been use...

Photoprotection of human skin beyond ultraviolet radiation.

PubMed

Grether-Beck, Susanne; Marini, Alessandra; Jaenicke, Thomas; Krutmann, Jean

2014-01-01

Photoprotection of human skin by means of sunscreens or daily skin-care products is traditionally centered around the prevention of acute (e.g. sunburn) and chronic (e.g. skin cancer and photoaging) skin damage that may result from exposure to ultraviolet rays (UVB and UVA). Within the last decade, however, it has been appreciated that wavelengths beyond the ultraviolet spectrum, in particular visible light and infrared radiation, contribute to skin damage in general and photoaging of human skin in particular. As a consequence, attempts have been made to develop skin care/sunscreen products that not only protect against UVB or UVA radiation but provide photoprotection against visible light and infrared radiation as well. In this article, we will briefly review the current knowledge about the mechanisms responsible for visible light/infrared radiation-induced skin damage and then, based on this information, discuss strategies that have been successfully used or may be employed in the future to achieve photoprotection of human skin beyond ultraviolet radiation. In this regard we will particularly focus on the use of topical antioxidants and the challenges that result from the task of showing their efficacy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cell damage caused by ultraviolet B radiation in the desert cyanobacterium Phormidium tenue and its recovery process.

PubMed

Wang, Gaohong; Deng, Songqiang; Liu, Jiafeng; Ye, Chaoran; Zhou, Xiangjun; Chen, Lanzhou

2017-10-01

Phormidium tenue, a cyanobacterium that grows in the topsoil of biological soil crusts (BSCs), has the highest recovery rate among desert crust cyanobacteria after exposure to ultraviolet B (UV-B) radiation. However, the mechanism underlying its recovery process is unclear. To address this issue, we measured chlorophyll a fluorescence, generation of reactive oxygen species (ROS), lipid peroxidation, and repair of DNA breakage in P. tenue following exposure to UV-B. We found that UV-B radiation at all doses tested reduced photosynthesis and induced cell damage in P. tenue. However, P. tenue responded to UV-B radiation by rapidly reducing photosynthetic activity, which protects the cell by leaking less ROS. Antioxidant enzymes, DNA damage repair systems, and UV absorbing pigments were then induced to mitigate the damage caused by UV-B radiation. The addition of exogenous antioxidant chemicals ascorbate and N-acetylcysteine also mitigated the harmful effects caused by UV-B radiation and enhanced the recovery process. These chemicals could aid in the resistance of P. tenue to the exposure of intense UV-B radiation in desertified areas when inoculated onto the sand surface to form artificial algal crusts. Copyright © 2017. Published by Elsevier Inc.

Ultraviolet radiation and nanoparticle induced intracellular free radicals generation measured in human keratinocytes by electron paramagnetic resonance spectroscopy.

PubMed

Rancan, F; Nazemi, B; Rautenberg, S; Ryll, M; Hadam, S; Gao, Q; Hackbarth, S; Haag, S F; Graf, C; Rühl, E; Blume-Peytavi, U; Lademann, J; Vogt, A; Meinke, M C

2014-05-01

Several nanoparticle-based formulations used in cosmetics and dermatology are exposed to sunlight once applied to the skin. Therefore, it is important to study possible synergistic effects of nanoparticles and ultraviolet radiation. Electron paramagnetic resonance spectroscopy (EPR) was used to detect intracellular free radicals induced by ultraviolet B (UVB) radiation and amorphous silica nanoparticle and to evaluate the influence of nanoparticle surface chemistry on particle cytotoxicity toward HaCaT cells. Uncoated titanium dioxide nanoparticles served as positive control. In addition, particle intracellular uptake, viability, and induction of interleukin-6 were measured. We found that photo-activated titanium dioxide particles induced a significant amount of intracellular free radicals. On the contrary, no intracellular free radicals were generated by the investigated silica nanoparticles in the dark as well as under UVB radiation. However, under UVB exposure, the non-functionalized silica nanoparticles altered the release of IL-6. At the same concentrations, the amino-functionalized silica nanoparticles had no influence on UVB-induced IL-6 release. EPR spectroscopy is a useful technique to measure nanoparticle-induced intracellular free radicals. Non-toxic concentrations of silica particles enhanced the toxicity of UVB radiation. This synergistic effect was not mediated by particle-generated free radicals and correlated with particle surface charge and intracellular distribution. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Photo-protection by 3-bromo-4, 5-dihydroxybenzaldehyde against ultraviolet B-induced oxidative stress in human keratinocytes.

PubMed

Hyun, Yu Jae; Piao, Mei Jing; Zhang, Rui; Choi, Yung Hyun; Chae, Sungwook; Hyun, Jin Won

2012-09-01

Exposure of the skin to ultraviolet B (UVB) radiation leads to epidermal damage and the generation of reactive oxygen species (ROS) in skin cells, including keratinocytes. Therefore, the photo-protective effect of 3-bromo-4, 5-dihydroxybenzaldehyde (BDB) against UVB was assessed in human HaCaT keratinocytes exposed to UVB radiation in vitro. BDB restored cell viability, which decreased upon exposure to UVB radiation. BDB exhibited scavenging activity against 1, 1-diphenyl-2-picrylhydrazyl radicals, intracellular ROS induced by hydrogen peroxide (H(2)O(2)) or UVB radiation, the superoxide anion generated by the xanthine/xanthine oxidase system, and the hydroxyl radical generated by the Fenton reaction (FeSO(4)+H(2)O(2)). Moreover, BDB absorbed UVB and decreased injury resulting from UVB-induced oxidative stress to lipids, proteins and DNA. Finally, BDB reduced UVB-induced apoptosis, as exemplified by fewer apoptotic bodies and a reduction in DNA fragmentation. Taken together, these results suggest that BDB protects human keratinocytes against UVB-induced oxidative stress by scavenging ROS and absorbing UVB rays, thereby reducing injury to cellular components. Copyright © 2012 Elsevier Inc. All rights reserved.

The Role of DNA Methylation Changes in Radiation-Induced Bystander Effects in cranial irradiated Mice

NASA Astrophysics Data System (ADS)

Zhang, Meng; Sun, Yeqing; Xue, Bei; Wang, Xinwen; Wang, Jiawen

2016-07-01

Heavy-ion radiation could lead to bystander effect in neighboring non-hit cells by signals released from directly-irradiated cells. The exact mechanisms of radiation-induced bystander effect in distant organ remain obscure, yet accumulating evidence points to the role of DNA methylation changes in bystander effect. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male Balb/c and C57BL mice were cranial exposed to 40, 200, 2000mGy dose of carbon heavy-ion radiation, while the rest of the animal body was shielded. The γH2AX foci as the DNA damage biomarker in directly irradiation organ ear and the distant organ liver were detected on 0, 1, 2, 6, 12 and 24h after radiation, respectively. Methylation-sensitive amplifcation polymorphism (MSAP) was used to monitor the level of polymorphic genomic DNA methylation changed with dose and time effects. The results show that cranial irradiated mice could induce the γH2AX foci and genomic DNA methylation changes significantly in both the directly irradiation organ ear and the distant organ liver. The percent of DNA methylation changes were time-dependent and tissue-specific. Demethylation polymorphism rate were highest separately at 1 h in 200 mGy and 6 h in 2000 mGy after irradiation in ear. The global DNA methylation changes tended to occur in the CG sites. We also found that the numbers of γH2AX foci and the genomic methylation changes of heavy-ion radiation-induced bystander effect in liver could be obvious 1 h after radiation and achieved the maximum at 6 h, while the changes could recover gradually at 12 h. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in both directly radiation organ ear and distant organ liver. Moreover, our findings are important to understand the molecular mechanism of radiation induced bystander effects in vivo. Keywords: Heavy-ion radiation; Bystander effect; DNA methylation; γH2

Complex DNA Damage: A Route to Radiation-Induced Genomic Instability and Carcinogenesis.

PubMed

Mavragani, Ifigeneia V; Nikitaki, Zacharenia; Souli, Maria P; Aziz, Asef; Nowsheen, Somaira; Aziz, Khaled; Rogakou, Emmy; Georgakilas, Alexandros G

2017-07-18

Cellular effects of ionizing radiation (IR) are of great variety and level, but they are mainly damaging since radiation can perturb all important components of the cell, from the membrane to the nucleus, due to alteration of different biological molecules ranging from lipids to proteins or DNA. Regarding DNA damage, which is the main focus of this review, as well as its repair, all current knowledge indicates that IR-induced DNA damage is always more complex than the corresponding endogenous damage resulting from endogenous oxidative stress. Specifically, it is expected that IR will create clusters of damage comprised of a diversity of DNA lesions like double strand breaks (DSBs), single strand breaks (SSBs) and base lesions within a short DNA region of up to 15-20 bp. Recent data from our groups and others support two main notions, that these damaged clusters are: (1) repair resistant, increasing genomic instability (GI) and malignant transformation and (2) can be considered as persistent "danger" signals promoting chronic inflammation and immune response, causing detrimental effects to the organism (like radiation toxicity). Last but not least, the paradigm shift for the role of radiation-induced systemic effects is also incorporated in this picture of IR-effects and consequences of complex DNA damage induction and its erroneous repair.

Effects of solar ultraviolet radiations on Bacillus subtilis spores and T-7 bacteriophage

NASA Technical Reports Server (NTRS)

Spizizen, J.; Isherwood, J. E.; Taylor, G. R.

1975-01-01

Spores of Bacillus subtilis HA 101 and the DNA polymerase I-defective mutant HA 101 (59)F were exposed to selected wavelengths of solar ultraviolet light and space vacuum during the return of Apollo 16. In addition, coliphage T-7 suspensions were exposed to solar ultraviolet radiation as part of the Microbial Response to Space Environment Experiment. Optical filters were employed to provide different energy levels at wavelengths 254 nm and 280 nm. Dose-response curves for lethal and mutagenic effects were compared with ground-based data. A close parallel was observed between the results of solar radiation and ground tests with spores of the two strains. However, significantly greater inactivation of T-7 bacteriophage was observed after exposure to solar ultraviolet radiation.

UV Radiation Damage and Bacterial DNA Repair Systems

ERIC Educational Resources Information Center

Zion, Michal; Guy, Daniel; Yarom, Ruth; Slesak, Michaela

2006-01-01

This paper reports on a simple hands-on laboratory procedure for high school students in studying both radiation damage and DNA repair systems in bacteria. The sensitivity to ultra-violet (UV) radiation of both "Escherichia coli" and "Serratia marcescens" is tested by radiating them for varying time periods. Two growth temperatures are used in…

Study of terahertz-radiation-induced DNA damage in human blood leukocytes

NASA Astrophysics Data System (ADS)

Angeluts, A. A.; Gapeyev, A. B.; Esaulkov, M. N.; Kosareva, O. G.; Matyunin, S. N.; Nazarov, M. M.; Pashovkin, T. N.; Solyankin, P. M.; Cherkasova, O. P.; Shkurinov, A. P.

2014-03-01

We have carried out the studies aimed at assessing the effect of terahertz radiation on DNA molecules in human blood leukocytes. Genotoxic testing of terahertz radiation was performed in three different oscillation regimes, the blood leukocytes from healthy donors being irradiated for 20 minutes with the mean intensity of 8 - 200 μW cm-2 within the frequency range of 0.1 - 6.5 THz. Using the comet assay it is shown that in the selected regimes such radiation does not induce a direct DNA damage in viable human blood leukocytes.

Chemiexcitation of Melanin Derivatives Induces DNA Photoproducts Long after UV Exposure

PubMed Central

Premi, Sanjay; Wallisch, Silvia; Mano, Camila M.; Weiner, Adam B.; Bacchiocchi, Antonella; Wakamatsu, Kazumasa; Bechara, Etelvino J. H.; Halaban, Ruth; Douki, Thierry; Brash, Douglas E.

2015-01-01

Mutations in sunlight-induced melanoma arise from cyclobutane pyrimidine dimers (CPD), DNA photoproducts that are typically created picoseconds after an ultraviolet (UV) photon is absorbed at thymine or cytosine. Here we show that in melanocytes, CPD are generated for >3 hours after exposure to UVA, a major component of the radiation in sunlight and in tanning beds. These “dark CPD” constitute the majority of CPD and include the cytosine-containing CPD that initiate UV-signature C→T mutations. Dark CPD arise when UV-induced reactive oxygen and nitrogen species combine to excite an electron in fragments of the pigment melanin. This creates a quantum triplet state that has the energy of a UV photon but that induces CPD by energy transfer to DNA in a radiation-independent manner. Melanin may thus be carcinogenic as well as protective against cancer. These findings also validate the long-standing suggestion that chemically-generated excited electronic states are relevant to mammalian biology. PMID:25700512

Complex DNA Damage: A Route to Radiation-Induced Genomic Instability and Carcinogenesis

PubMed Central

Mavragani, Ifigeneia V.; Nikitaki, Zacharenia; Souli, Maria P.; Aziz, Asef; Nowsheen, Somaira; Aziz, Khaled; Rogakou, Emmy

2017-01-01

Cellular effects of ionizing radiation (IR) are of great variety and level, but they are mainly damaging since radiation can perturb all important components of the cell, from the membrane to the nucleus, due to alteration of different biological molecules ranging from lipids to proteins or DNA. Regarding DNA damage, which is the main focus of this review, as well as its repair, all current knowledge indicates that IR-induced DNA damage is always more complex than the corresponding endogenous damage resulting from endogenous oxidative stress. Specifically, it is expected that IR will create clusters of damage comprised of a diversity of DNA lesions like double strand breaks (DSBs), single strand breaks (SSBs) and base lesions within a short DNA region of up to 15–20 bp. Recent data from our groups and others support two main notions, that these damaged clusters are: (1) repair resistant, increasing genomic instability (GI) and malignant transformation and (2) can be considered as persistent “danger” signals promoting chronic inflammation and immune response, causing detrimental effects to the organism (like radiation toxicity). Last but not least, the paradigm shift for the role of radiation-induced systemic effects is also incorporated in this picture of IR-effects and consequences of complex DNA damage induction and its erroneous repair. PMID:28718816

Using natural dietary sources of antioxidants to protect against ultraviolet and visible radiation-induced DNA damage: an investigation of human green tea ingestion.

PubMed

Malhomme de la Roche, Helena; Seagrove, Susan; Mehta, Anisha; Divekar, Preshita; Campbell, Sandra; Curnow, Alison

2010-11-03

Oral ingestion of green tea is a potent dietary source of antioxidant polyphenols. These compounds are of interest as they may be able to provide additional protection to the body to help prevent the deleterious effects of ultraviolet A and visible radiation (UVA/VIS) produced indirectly via reactive oxygen species (ROS) in sunlight exposed skin. A small clinical study was conducted in ten healthy adult volunteers. Samples of whole blood were obtained from each before and 30, 60 and 90 min following ingestion of three breakfast cups of green tea (540 ml in total) prepared in a standardised manner. Peripheral leucocytes were isolated from each blood sample and exposed to increasing periods of UVA/VIS irradiation in the laboratory (0, 9, 12 or 18 min). Alkaline single cell gel electrophoresis (the comet assay) was then conducted to determine the level of DNA damage in each sample from each individual. The findings support those of our previous pilot study and indicate that drinking green tea did significantly reduce the genotoxic effects observed in peripheral blood cells 60 min following ingestion when artificially exposed to 12 min of UVA/VIS irradiation in the laboratory. It is postulated that this protection is afforded by the polyphenol compounds (known to be contained within green tea) via scavenging or quenching of the damaging ROS induced by this form of light exposure. Further investigation should consider whether this dietary-induced protection could be extended to cells of the skin. Copyright © 2010 Elsevier B.V. All rights reserved.

[UV-induced DNA damage and protective effects of antioxidants on DNA damage in human lens epithelial cells studied with comet assay].

PubMed

Wu, Zhi-hong; Wang, Mian-rong; Yan, Qi-chang; Pu, Wei; Zhang, Jin-song

2006-11-01

To investigate the mechanism of UV-induced DNA damage and repair and the protective effects of antioxidants on DNA damage in human lens epithelial cells. Human lens epithelial cells were irradiated at UV-doses 0.0 (control group), 2.5, 5.0, 7.5, 10.0 mJ/cm(2) (treated group 1 - 4). The amounts of DNA single strand breaks (SSB) were measured with the alkaline comet assay (CA). The spontaneous repair of DNA SSB after exposure to UV at 10.0 mJ/cm(2) was also determined in human lens epithelial cells. Human lens epithelial cells were treated with different concentration of VitaminC (VitC), taurine, superoxide dismutase (SOD) and epigallocatechin gallate (EGCG) before and after ultraviolet radiation, the effects of antioxidants on DNA damage was examined with alkaline comet assay. The amount of DNA SSB in control group and treated groups 1 - 4 showed increased tendency, was dose-dependent to the dose of UV irradiation, the differences of DNA SSB in 5 group were significantly (P < 0.01). UV-induced DNA SSB at 10.0 mJ/cm(2) in human lens epithelial cells, the half repair time was 60 minutes. Human lens epithelial cells were treated with different concentrations of taurine, SOD and EGCG before ultraviolet radiation. The differences of DNA damage in control and various antioxidant treated groups was statistically significant (F = 6.591, 13.542, 4.626 in cells treated with taurine, SOD and EGCG, respectively, P < 0.01), the difference of VitC effect on DNA in control and treated group were not significantly (F = 1.451, P > 0.05). Human lens epithelial cells were treated with different concentration of VitC, taurine, SOD and EGCG after ultraviolet radiation. The differences of DNA damage between the control and treated group were statistically significant (F = 6.571, 4.810, 6.824, 9.182 in cells treated with VitC, taurine, SOD and EGCG, respectively, P < 0.01). The differences of protective effects on DNA damage in these four different kinds of antioxidants added before UV

Mitochondria regulate DNA damage and genomic instability induced by high LET radiation

NASA Astrophysics Data System (ADS)

Zhang, Bo; Davidson, Mercy M.; Hei, Tom K.

2014-04-01

High linear energy transfer (LET) radiation including α particles and heavy ions is the major type of radiation found in space and is considered a potential health risk for astronauts. Even though the chance that these high LET particles traversing through the cytoplasm of cells is higher than that through the nuclei, the contribution of targeted cytoplasmic irradiation to the induction of genomic instability and other chromosomal damages induced by high LET radiation is not known. In the present study, we investigated whether mitochondria are the potential cytoplasmic target of high LET radiation in mediating cellular damage using a mitochondrial DNA (mtDNA) depleted (ρ0) human small airway epithelial (SAE) cell model and a precision charged particle microbeam with a beam width of merely one micron. Targeted cytoplasmic irradiation by high LET α particles induced DNA oxidative damage and double strand breaks in wild type ρ+ SAE cells. Furthermore, there was a significant increase in autophagy and micronuclei, which is an indication of genomic instability, together with the activation of nuclear factor kappa-B (NF-κB) and mitochondrial inducible nitric oxide synthase (iNOS) signaling pathways in ρ+ SAE cells. In contrast, ρ0 SAE cells exhibited a significantly lower response to these same endpoints examined after cytoplasmic irradiation with high LET α particles. The results indicate that mitochondria are essential in mediating cytoplasmic radiation induced genotoxic damage in mammalian cells. Furthermore, the findings may shed some light in the design of countermeasures for space radiation.

ULTRAVIOLET RADIATION AND ARSENIC INTERACTIONS: EFFECTS ON CLADOCERANS

EPA Science Inventory

The effects of arsenic and ultraviolet radiation (UV) on cladocerans have been examined separately, however the interaction of these two stresses has not been explored. Potential synergism between these two stresses is possible as arsenic is known to inhibit repair of UV induced ...

Both Complexity and Location of DNA Damage Contribute to Cellular Senescence Induced by Ionizing Radiation

PubMed Central

Zhang, Xurui; Ye, Caiyong; Sun, Fang; Wei, Wenjun; Hu, Burong; Wang, Jufang

2016-01-01

Persistent DNA damage is considered as a main cause of cellular senescence induced by ionizing radiation. However, the molecular bases of the DNA damage and their contribution to cellular senescence are not completely clear. In this study, we found that both heavy ions and X-rays induced senescence in human uveal melanoma 92–1 cells. By measuring senescence associated-β-galactosidase and cell proliferation, we identified that heavy ions were more effective at inducing senescence than X-rays. We observed less efficient repair when DNA damage was induced by heavy ions compared with X-rays and most of the irreparable damage was complex of single strand breaks and double strand breaks, while DNA damage induced by X-rays was mostly repaired in 24 hours and the remained damage was preferentially associated with telomeric DNA. Our results suggest that DNA damage induced by heavy ion is often complex and difficult to repair, thus presents as persistent DNA damage and pushes the cell into senescence. In contrast, persistent DNA damage induced by X-rays is preferentially associated with telomeric DNA and the telomere-favored persistent DNA damage contributes to X-rays induced cellular senescence. These findings provide new insight into the understanding of high relative biological effectiveness of heavy ions relevant to cancer therapy and space radiation research. PMID:27187621

DELAY OF CLEAVAGE OF THE ARBACIA EGG BY ULTRAVIOLET RADIATION

PubMed Central

Blum, Harold F.; Price, Judith P.

1950-01-01

While our data do not permit us to state the exact locus or mode of action of ultraviolet radiation in the Arbacia egg, certain general conclusions may be reached. The amount of delay of cleavage of these eggs is determined by two principal factors: (1) The extent of an effect, resulting from photochemical action induced by ultraviolet radiation, which is reversible in a biological sense, the reversibility not being directly dependent upon the process of cell division. (2) The sensitivity of the cell division process to the effects of the ultraviolet-induced photochemical reaction. This factor varies with the stage of cell division, the cell being insensitive during a period corresponding to most of mitosis. It seems likely that these findings may apply to cell division in general, but, since the quantitative relationships observed must, in this case, reflect the integration of two semi-independent factors, the over-all picture may appear quite different for different kinds of cells. PMID:15410486

Nuclear DNA damage-triggered NLRP3 inflammasome activation promotes UVB-induced inflammatory responses in human keratinocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hasegawa, Tatsuya, E-mail: tatsuya.hasegawa@to.shiseido.co.jp; Nakashima, Masaya; Suzuki, Yoshiharu

Ultraviolet (UV) radiation in sunlight can result in DNA damage and an inflammatory reaction of the skin commonly known as sunburn, which in turn can lead to cutaneous tissue disorders. However, little has been known about how UV-induced DNA damage mediates the release of inflammatory mediators from keratinocytes. Here, we show that UVB radiation intensity-dependently increases NLRP3 gene expression and IL-1β production in human keratinocytes. Knockdown of NLRP3 with siRNA suppresses UVB-induced production of not only IL-1β, but also other inflammatory mediators, including IL-1α, IL-6, TNF-α, and PGE{sub 2}. In addition, inhibition of DNA damage repair by knockdown of XPA,more » which is a major component of the nucleotide excision repair system, causes accumulation of cyclobutane pyrimidine dimer (CPD) and activation of NLRP3 inflammasome. In vivo immunofluorescence analysis confirmed that NLRP3 expression is also elevated in UV-irradiated human epidermis. Overall, our findings indicate that UVB-induced DNA damage initiates NLRP3 inflammasome activation, leading to release of various inflammatory mediators from human keratinocytes. - Highlights: • UVB radiation induces NLRP3 inflammasome activation in human keratinocytes. • NLRP3 knockdown suppresses production of UVB-induced inflammatory mediators. • UVB-induced DNA damage triggers NLRP3 inflammasome activation. • NLRP3 expression in human epidermis is elevated in response to UV radiation.« less

EPA attenuates ultraviolet radiation-induced downregulation of aquaporin-3 in human keratinocytes.

PubMed

Jeon, Byoung-Kook; Kang, Moon-Kyung; Lee, Ghang-Tai; Lee, Kun-Kuk; Lee, Ho-Sub; Woo, Won-Hong; Mun, Yeun-Ja

2015-08-01

Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid (ω-3 PUFA) that protects against photodamage and photocarcinogenesis in mammals. Aquaporin-3 (AQP3) is a water/glycerol transport protein that is found in basal layer keratinocytes. In this study, we have investigated the protective effect of EPA against ultraviolet B (UVB)-induced AQP3 downregulation in human keratinocytes. EPA treatment was found to increase AQP3 gene and protein expression in human epidermal keratinocytes (HaCaT). Using a specific inhibitor, we observed that the effect of EPA on AQP3 expression was mediated by extracellular signal-regulated kinase (ERK) activation. UVB radiation induced AQP3 downregulation in HaCaT cells, and it was found that EPA treatment attenuated UVB-induced AQP3 reduction and the associated cell death. UVB-induced downregulation of AQP3 was blocked by EPA and p38 inhibitor SB203580. Collectively, the present results show that EPA increased AQP3 expression and that this led to a reduction UVB-induced photodamage.

Redundancy of mammalian Y family DNA polymerases in cellular responses to genomic DNA lesions induced by ultraviolet light

PubMed Central

Jansen, Jacob G.; Temviriyanukul, Piya; Wit, Niek; Delbos, Frédéric; Reynaud, Claude-Agnès; Jacobs, Heinz; de Wind, Niels

2014-01-01

Short-wave ultraviolet light induces both mildly helix-distorting cyclobutane pyrimidine dimers (CPDs) and severely distorting (6–4) pyrimidine pyrimidone photoproducts ((6–4)PPs). The only DNA polymerase (Pol) that is known to replicate efficiently across CPDs is Polη, a member of the Y family of translesion synthesis (TLS) DNA polymerases. Phenotypes of Polη deficiency are transient, suggesting redundancy with other DNA damage tolerance pathways. Here we performed a comprehensive analysis of the temporal requirements of Y-family Pols ι and κ as backups for Polη in (i) bypassing genomic CPD and (6–4)PP lesions in vivo, (ii) suppressing DNA damage signaling, (iii) maintaining cell cycle progression and (iv) promoting cell survival, by using mouse embryonic fibroblast lines with single and combined disruptions in these Pols. The contribution of Polι is restricted to TLS at a subset of the photolesions. Polκ plays a dominant role in rescuing stalled replication forks in Polη-deficient mouse embryonic fibroblasts, both at CPDs and (6–4)PPs. This dampens DNA damage signaling and cell cycle arrest, and results in increased survival. The role of relatively error-prone Pols ι and κ as backups for Polη contributes to the understanding of the mutator phenotype of xeroderma pigmentosum variant, a syndrome caused by Polη defects. PMID:25170086

Perilla frutescens leaves extract ameliorates ultraviolet radiation-induced extracellular matrix damage in human dermal fibroblasts and hairless mice skin.

PubMed

Bae, Jung-Soo; Han, Mira; Shin, Hee Soon; Kim, Min-Kyoung; Shin, Chang-Yup; Lee, Dong Hun; Chung, Jin Ho

2017-01-04

Perilla frutescens (L.) Britt. (Lamiaceae) is a traditional herb that is consumed in East Asian countries as a traditional medicine. This traditional herb has been documented for centuries to treat various diseases such as depression, allergies, inflammation and asthma. However, the effect of Perilla frutescens on skin has not been characterized well. The present study aimed to investigate the effect of Perilla frutescens leaves extract (PLE) on ultraviolet radiation-induced extracellular matrix damage in human dermal fibroblasts and hairless mice skin. Human dermal fibroblasts and Skh-1 hairless mice were irradiated with UV and treated with PLE. Protein and mRNA levels of various target molecules were analyzed by western blotting and quantitative RT-PCR, respectively. Histological changes of mouse skin were analyzed by H&E staining. To elucidate underlying mechanism of PLE, activator protein-1 (AP-1) DNA binding assay and the measurement of reactive oxygen species (ROS) were performed. PLE significantly inhibited basal and UV-induced MMP-1 and MMP-3 expression dose-dependently, and also decreased UV-induced phosphorylation of extracellular signal-regulated kinases and c-Jun N-terminal kinases. This inhibitory effects of PLE on MMP-1 and MMP-3 were mediated by reduction of ROS generation and AP-1 DNA binding activity induced by UV. Furthermore, PLE promoted type I procollagen production irrespective of UV irradiation. In the UV-irradiated animal model, PLE significantly reduced epidermal skin thickness and MMP-13 expression induced by UV. Our results demonstrate that PLE has the protective effect against UV-induced dermal matrix damage. Therefore, we suggest that PLE can be a potential agent for prevention of skin aging. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Vacuum and ultraviolet radiation effects on binders and pigments for spacecraft thermal control coatings

NASA Technical Reports Server (NTRS)

Progar, D. J.; Wade, W. R.

1971-01-01

An evaluation of several silicone resin binders and powdered inorganic pigments for potential use in spacecraft thermal-control paint formulations is presented. The pigments were selected on the basis of a hypothesis relating the heat of formation of a compound to the compound's resistance to ultra-radiation-induced degradation. Reflectance measurements were made in situ to determine degradation rates due to ultraviolet radiation. The tested polydimethylsiloxane resins were not significantly affected by long exposures to ultraviolet radiation. All the pigments, which were dispersed in a polydimethylsiloxane resin, were degraded by ultraviolet radiation as determined by an increase of solar absorptance. For the materials evaluated in this study, no evidence was found to indicate that pigments with high heats of formation were resistant to ultraviolet degradation.

Protective effect of cerium ion against ultraviolet B radiation-induced water stress in soybean seedlings.

PubMed

Mao, Chun Xia; Chen, Min Min; Wang, Lei; Zou, Hua; Liang, Chan Juan; Wang, Li Hong; Zhou, Qing

2012-06-01

Effects of cerium ion (Ce(III)) on water relations of soybean seedlings (Glycine max L.) under ultraviolet B radiation (UV-B, 280-320 nm) stress were investigated under laboratory conditions. UV-B radiation not only affected the contents of two osmolytes (proline, soluble sugar) in soybean seedlings, but also inhibited the transpiration in soybean seedlings by decreasing the stomatal density and conductance. The two effects caused the inhibition in the osmotic and metabolic absorption of water, which decreased the water content and the free water/bound water ratio. Obviously, UV-B radiation led to water stress, causing the decrease in the photosynthesis in soybean seedlings. The pretreatment with 20 mg L(-1) Ce(III) could alleviate UV-B-induced water stress by regulating the osmotic and metabolic absorption of water in soybean seedlings. The alleviated effect caused the increase in the photosynthesis and the growth of soybean seedlings. It is one of the protective effect mechanisms of Ce(III) against the UV-B radiation-induced damage to plants.

Identification of potentially cytotoxic lesions induced by UVA photoactivation of DNA 4-thiothymidine in human cells

PubMed Central

Reelfs, Olivier; Macpherson, Peter; Ren, Xiaolin; Xu, Yao-Zhong; Karran, Peter; Young, Antony R.

2011-01-01

Photochemotherapy—in which a photosensitizing drug is combined with ultraviolet or visible radiation—has proven therapeutic effectiveness. Existing approaches have drawbacks, however, and there is a clinical need to develop alternatives offering improved target cell selectivity. DNA substitution by 4-thiothymidine (S4TdR) sensitizes cells to killing by ultraviolet A (UVA) radiation. Here, we demonstrate that UVA photoactivation of DNA S4TdR does not generate reactive oxygen or cause direct DNA breakage and is only minimally mutagenic. In an organotypic human skin model, UVA penetration is sufficiently robust to kill S4TdR-photosensitized epidermal cells. We have investigated the DNA lesions responsible for toxicity. Although thymidine is the predominant UVA photoproduct of S4TdR in dilute solution, more complex lesions are formed when S4TdR-containing oligonucleotides are irradiated. One of these, a thietane/S5-(6-4)T:T, is structurally related to the (6-4) pyrimidine:pyrimidone [(6-4) Py:Py] photoproducts induced by UVB/C radiation. These lesions are detectable in DNA from S4TdR/UVA-treated cells and are excised from DNA more efficiently by keratinocytes than by leukaemia cells. UVA irradiation also induces DNA interstrand crosslinking of S4TdR-containing duplex oligonucleotides. Cells defective in repairing (6-4) Py:Py DNA adducts or processing DNA crosslinks are extremely sensitive to S4TdR/UVA indicating that these lesions contribute significantly to S4TdR/UVA cytotoxicity. PMID:21890905

Inactivation of NADPH oxidases NOX4 and NOX5 protects human primary fibroblasts from ionizing radiation-induced DNA damage.

PubMed

Weyemi, Urbain; Redon, Christophe E; Aziz, Towqir; Choudhuri, Rohini; Maeda, Daisuke; Parekh, Palak R; Bonner, Michael Y; Arbiser, Jack L; Bonner, William M

2015-03-01

Human exposure to ionizing radiation from medical procedures has increased sharply in the last three decades. Recent epidemiological studies suggest a direct relationship between exposure to ionizing radiation and health problems, including cancer incidence. Therefore, minimizing the impact of radiation exposure in patients has become a priority in the development of future clinical practices. Crucial players in radiation-induced DNA damage include reactive oxygen species (ROS), but the sources of these have remained elusive. To the best of our knowledge, we show here for the first time that two members of the ROS-generating NADPH oxidase family (NOXs), NOX4 and NOX5, are involved in radiation-induced DNA damage. Depleting these two NOXs in human primary fibroblasts resulted in reduced levels of DNA damage as measured by levels of radiation-induced foci, a marker of DNA double-strand breaks (DSBs) and the comet assay coupled with increased cell survival. NOX involvement was substantiated with fulvene-5, a NOXs-specific inhibitor. Moreover, fulvene-5 mitigated radiation-induced DNA damage in human peripheral blood mononuclear cells ex vivo. Our results provide evidence that the inactivation of NOXs protects cells from radiation-induced DNA damage and cell death. These findings suggest that NOXs inhibition may be considered as a future pharmacological target to help minimize the negative effects of radiation exposure for millions of patients each year.

Inactivation of NADPH Oxidases NOX4 and NOX5 Protects Human Primary Fibroblasts from Ionizing Radiation-Induced DNA Damage

PubMed Central

Weyemi, Urbain; Redon, Christophe E.; Aziz, Towqir; Choudhuri, Rohini; Maeda, Daisuke; Parekh, Palak R.; Bonner, Michael Y.; Arbiser, Jack L.; Bonner, William M.

2015-01-01

Human exposure to ionizing radiation from medical procedures has increased sharply in the last three decades. Recent epidemiological studies suggest a direct relationship between exposure to ionizing radiation and health problems, including cancer incidence. Therefore, minimizing the impact of radiation exposure in patients has become a priority in the development of future clinical practices. Crucial players in radiation-induced DNA damage include reactive oxygen species (ROS), but the sources of these have remained elusive. To the best of our knowledge, we show here for the first time that two members of the ROS-generating NADPH oxidase family (NOXs), NOX4 and NOX5, are involved in radiation-induced DNA damage. Depleting these two NOXs in human primary fibroblasts resulted in reduced levels of DNA damage as measured by levels of radiation-induced foci, a marker of DNA double-strand breaks (DSBs) and the comet assay coupled with increased cell survival. NOX involvement was substantiated with fulvene-5, a NOXs-specific inhibitor. Moreover, fulvene-5 mitigated radiation-induced DNA damage in human peripheral blood mononuclear cells ex vivo. Our results provide evidence that the inactivation of NOXs protects cells from radiation-induced DNA damage and cell death. These findings suggest that NOXs inhibition may be considered as a future pharmacological target to help minimize the negative effects of radiation exposure for millions of patients each year. PMID:25706776

Solar ultraviolet radiation cataract.

PubMed

Löfgren, Stefan

2017-03-01

Despite being a treatable disease, cataract is still the leading cause for blindness in the world. Solar ultraviolet radiation is epidemiologically linked to cataract development, while animal and in vitro studies prove a causal relationship. However, the pathogenetic pathways for the disease are not fully understood and there is still no perfect model for human age related cataract. This non-comprehensive overview focus on recent developments regarding effects of solar UV radiation wavebands on the lens. A smaller number of fundamental papers are also included to provide a backdrop for the overview. Future studies are expected to further clarify the cellular and subcellular mechanisms for UV radiation-induced cataract and especially the isolated or combined temporal and spatial effects of UVA and UVB in the pathogenesis of human cataract. Regardless of the cause for cataract, there is a need for advances in pharmaceutical or other treatment modalities that do not require surgical replacement of the lens. Copyright © 2016. Published by Elsevier Ltd.

Ultraviolet Radiations: Skin Defense-Damage Mechanism.

PubMed

Mohania, Dheeraj; Chandel, Shikha; Kumar, Parveen; Verma, Vivek; Digvijay, Kumar; Tripathi, Deepika; Choudhury, Khushboo; Mitten, Sandeep Kumar; Shah, Dilip

2017-01-01

UV-radiations are the invisible part of light spectra having a wavelength between visible rays and X-rays. Based on wavelength, UV rays are subdivided into UV-A (320-400 nm), UV-B (280-320 nm) and UV-C (200-280 nm). Ultraviolet rays can have both harmful and beneficial effects. UV-C has the property of ionization thus acting as a strong mutagen, which can cause immune-mediated disease and cancer in adverse cases. Numbers of genetic factors have been identified in human involved in inducing skin cancer from UV-radiations. Certain heredity diseases have been found susceptible to UV-induced skin cancer. UV radiations activate the cutaneous immune system, which led to an inflammatory response by different mechanisms. The first line of defense mechanism against UV radiation is melanin (an epidermal pigment), and UV absorbing pigment of skin, which dissipate UV radiation as heat. Cell surface death receptor (e.g. Fas) of keratinocytes responds to UV-induced injury and elicits apoptosis to avoid malignant transformation. In addition to the formation of photo-dimers in the genome, UV also can induce mutation by generating ROS and nucleotides are highly susceptible to these free radical injuries. Melanocortin 1 receptor (MC1R) has been known to be implicated in different UV-induced damages such as pigmentation, adaptive tanning, and skin cancer. UV-B induces the formation of pre-vitamin D3 in the epidermal layer of skin. UV-induced tans act as a photoprotection by providing a sun protection factor (SPF) of 3-4 and epidermal hyperplasia. There is a need to prevent the harmful effects and harness the useful effects of UV radiations.

Biological Sensors for Solar Ultraviolet Radiation

PubMed Central

Yagura, Teiti; Makita, Kazuo; Yamamoto, Hiromasa; Menck, Carlos F.M.; Schuch, André P.

2011-01-01

Solar ultraviolet (UV) radiation is widely known as a genotoxic environmental agent that affects Earth ecosystems and the human population. As a primary consequence of the stratospheric ozone layer depletion observed over the last decades, the increasing UV incidence levels have heightened the concern regarding deleterious consequences affecting both the biosphere and humans, thereby leading to an increase in scientific efforts to understand the role of sunlight in the induction of DNA damage, mutagenesis, and cell death. In fact, the various UV-wavelengths evoke characteristic biological impacts that greatly depend on light absorption of biomolecules, especially DNA, in living organisms, thereby justifying the increasing importance of developing biological sensors for monitoring the harmful impact of solar UV radiation under various environmental conditions. In this review, several types of biosensors proposed for laboratory and field application, that measure the biological effects of the UV component of sunlight, are described. Basically, the applicability of sensors based on DNA, bacteria or even mammalian cells are presented and compared. Data are also presented showing that on using DNA-based sensors, the various types of damage produced differ when this molecule is exposed in either an aqueous buffer or a dry solution. Apart from the data thus generated, the development of novel biosensors could help in evaluating the biological effects of sunlight on the environment. They also emerge as alternative tools for using live animals in the search for protective sunscreen products. PMID:22163847

Whey peptides prevent chronic ultraviolet B radiation-induced skin aging in melanin-possessing male hairless mice.

PubMed

Kimura, Yoshiyuki; Sumiyoshi, Maho; Kobayashi, Toshiya

2014-01-01

Whey proteins or peptides exhibit various actions, including an antioxidant action, an anticancer action, and a protective action against childhood asthma and atopic syndrome. The effects of orally administered whey peptides (WPs) on chronic ultraviolet B (UVB) radiation-induced cutaneous changes, including changes in cutaneous thickness, elasticity, wrinkle formation, etc., have not been examined. In this study, we studied the preventive effects of WPs on cutaneous aging induced by chronic UVB irradiation in melanin-possessing male hairless mice (HRM). UVB (36-180 mJ/cm(2)) was irradiated to the dorsal area for 17 wk in HRM, and the measurements of cutaneous thickness and elasticity in UVB irradiated mice were performed every week. WPs (200 and 400 mg/kg, twice daily) were administered orally for 17 wk. WPs inhibited the increase in cutaneous thickness, wrinkle formation, and melanin granules and the reduction in cutaneous elasticity associated with photoaging. Furthermore, it has been reported that UVB irradiation-induced skin aging is closely associated with the increase in expression of matrix metalloproteinase (MMP), vascular endothelial growth factor (VEGF), Ki-67-, and 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells. WPs also prevented increases in the expression of MMP-2 and pro-MMP-9, VEGF, and Ki-67- and 8-OHdG-positive cells induced by chronic UVB irradiation. It was found that WPs prevent type IV collagen degradation, angiogenesis, proliferation, and DNA damage caused by UVB irradiation. Overall, these results demonstrate the considerable benefit of WPs for protection against solar UV-irradiated skin aging as a supplemental nutrient.

Ursolic Acid-Regulated Energy Metabolism—Reliever or Propeller of Ultraviolet-Induced Oxidative Stress and DNA Damage?

PubMed Central

Lee, Yuan-Hao; Sun, Youping; Glickman, Randolph D.

2014-01-01

Ultraviolet (UV) light is a leading cause of diseases, such as skin cancers and cataracts. A main process mediating UV-induced pathogenesis is the production of reactive oxygen species (ROS). Excessive ROS levels induce the formation of DNA adducts (e.g., pyrimidine dimers) and result in stalled DNA replication forks. In addition, ROS promotes phosphorylation of tyrosine kinase-coupled hormone receptors and alters downstream energy metabolism. With respect to the risk of UV-induced photocarcinogenesis and photodamage, the antitumoral and antioxidant functions of natural compounds become important for reducing UV-induced adverse effects. One important question in the field is what determines the differential sensitivity of various types of cells to UV light and how exogenous molecules, such as phytochemicals, protect normal cells from UV-inflicted damage while potentiating tumor cell death, presumably via interaction with intracellular target molecules and signaling pathways. Several endogenous molecules have emerged as possible players mediating UV-triggered DNA damage responses. Specifically, UV activates the PIKK (phosphatidylinositol 3-kinase-related kinase) family members, which include DNA-PKcs, ATM (ataxia telangiectasia mutated) and mTOR (mammalian target of rapamycin), whose signaling can be affected by energy metabolism; however, it remains unclear to what extent the activation of hormone receptors regulates PIKKs and whether this crosstalk occurs in all types of cells in response to UV. This review focuses on proteomic descriptions of the relationships between cellular photosensitivity and the phenotypic expression of the insulin/insulin-like growth receptor. It covers the cAMP-dependent pathways, which have recently been shown to regulate the DNA repair machinery through interactions with the PIKK family members. Finally, this review provides a strategic illustration of how UV-induced mitogenic activity is modulated by the insulin sensitizer, ursolic

Clustered DNA damages induced by high and low LET radiation, including heavy ions

NASA Technical Reports Server (NTRS)

Sutherland, B. M.; Bennett, P. V.; Schenk, H.; Sidorkina, O.; Laval, J.; Trunk, J.; Monteleone, D.; Sutherland, J.; Lowenstein, D. I. (Principal Investigator)

2001-01-01

Clustered DNA damages--here defined as two or more lesions (strand breaks, oxidized purines, oxidized pyrimidines or abasic sites) within a few helical turns--have been postulated as difficult to repair accurately, and thus highly significant biological lesions. Further, attempted repair of clusters may produce double strand breaks (DSBs). However, until recently, there was no way to measure ionizing radiation-induced clustered damages, except DSB. We recently described an approach for measuring classes of clustered damages (oxidized purine clusters, oxidized pyrimidine clusters, abasic clusters, along with DSB). We showed that ionizing radiation (gamma rays and Fe ions, 1 GeV/amu) does induce such clusters in genomic DNA in solution and in human cells. These studies also showed that each damage cluster results from one radiation hit (and its track), thus indicating that they can be induced by very low doses of radiation, i.e. two independent hits are not required for cluster induction. Further, among all complex damages, double strand breaks comprise--at most-- 20%, with the other clustered damages being at least 80%.

Excision repair of UV radiation-induced DNA damage in Caenorhabditis elegans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hartman, P.S.; Hevelone, J.; Dwarakanath, V.

1989-06-01

Radioimmunoassays were used to monitor the removal of antibody-binding sites associated with the two major UV radiation-induced DNA photoproducts (cyclobutane dimers and (6-4) photoproducts). Unlike with cultured human cells, where (6-4) photoproducts are removed more rapidly than cyclobutane dimers, the kinetics of repair were similar for both lesions. Repair capacity in wild type diminished throughout development. The radioimmunoassays were also employed to confirm the absence of photoreactivation in C. elegans. In addition, three radiation-sensitive mutants (rad-1, rad-2, rad-7) displayed normal repair capacities. An excision defect was much more pronounced in larvae than embryos in the fourth mutant tested (rad-3). Thismore » correlates with the hypersensitivity pattern of this mutant and suggests that DNA repair may be developmentally regulated in C. elegans. The mechanism of DNA repair in C. elegans as well as the relationship between the repair of specific photoproducts and UV radiation sensitivity during development are discussed.« less

Leptin deficiency-induced obesity exacerbates ultraviolet B radiation-induced cyclooxygenase-2 expression and cell survival signals in ultraviolet B-irradiated mouse skin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharma, Som D.; Katiyar, Santosh K., E-mail: skatiyar@uab.ed; Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294

Obesity has been implicated in several inflammatory diseases and in different types of cancer. Chronic inflammation induced by exposure to ultraviolet (UV) radiation has been implicated in various skin diseases, including melanoma and nonmelanoma skin cancers. As the relationship between obesity and susceptibility to UV radiation-caused inflammation is not clearly understood, we assessed the role of obesity on UVB-induced inflammation, and mediators of this inflammatory response, using the genetically obese (leptin-deficient) mouse model. Leptin-deficient obese (ob/ob) mice and wild-type counterparts (C57/BL6 mice) were exposed to UVB radiation (120 mJ/cm{sup 2}) on alternate days for 1 month. The mice were thenmore » euthanized and skin samples collected for analysis of biomarkers of inflammatory responses using immunohistochemistry, western blotting, ELISA and real-time PCR. Here, we report that the levels of inflammatory responses were higher in the UVB-exposed skin of the ob/ob obese mice than those in the UVB-exposed skin of the wild-type non-obese mice. The levels of UVB-induced cyclooxygenase-2 expression, prostaglandin-E{sub 2} production, proinflammatory cytokines (i.e., tumor necrosis factor-alpha, interleukin-1beta, interleukin-6), and proliferating cell nuclear antigen and cell survival signals (phosphatidylinositol-3-kinase and p-Akt-Ser{sup 473}) were higher in the skin of the ob/ob obese mice than the those in skin of their wild-type non-obese counterparts. Compared with the wild-type non-obese mice, the leptin-deficient obese mice also exhibited greater activation of NF-kappaB/p65 and fewer apoptotic cells in the UVB-irradiated skin. Our study suggests for the first time that obesity in mice is associated with greater susceptibility to UVB-induced inflammatory responses and, therefore, obesity may increase susceptibility to UVB-induced inflammation-associated skin diseases, including the risk of skin cancer.« less

An immunohistochemical panel to assess ultraviolet radiation-associated oxidative skin injury.

PubMed

Mamalis, A; Fiadorchanka, N; Adams, L; Serravallo, M; Heilman, E; Siegel, D; Brody, N; Jagdeo, J

2014-05-01

Ultraviolet (UV) radiation results in a significant loss in years of healthy life, approximately 1.5 million disability-adjusted life years (DALYs), and is associated with greater than 60,000 deaths annually worldwide that are attributed to melanoma and other skin cancers. Currently, there are no standardized biomarkers or assay panels to assess oxidative stress skin injury patterns in human skin exposed to ionizing radiation. Using biopsy specimens from chronic solar UV-exposed and UV-protected skin, we demonstrate that UV radiation-induced oxidative skin injury can be evaluated by an immunohistochemical panel that stains 8-hydroxydeoxyguanosine (8-OH-dG) to assess DNA adducts, 4-hydroxy-2-nonenal (HNE) to assess lipid peroxidation, and advanced glycation end products (AGEs) to assess protein damage. We believe this panel contains the necessary cellular biomarkers to evaluate topical agents, such as sunscreens and anti-oxidants that are designed to prevent oxidative skin damage and may reduce UV-associated skin aging, carcinogenesis, and inflammatory skin diseases. We envision that this panel will become an important tool for researchers developing topical agents to protect against UV radiation and other oxidants and ultimately lead to reductions in lost years of healthy life, DALYs, and annual deaths associated with UV radiation.

Ultraviolet radiation changes

NASA Technical Reports Server (NTRS)

Mckenzie, Richard L.; Frederick, John E.; Ilyas, Mohammad; Filyushkin, V.; Wahner, Andreas; Stamnes, K.; Muthusubramanian, P.; Blumthaler, M.; Roy, Colin E.; Madronich, Sasha

1991-01-01

A major consequence of ozone depletion is an increase in solar ultraviolet (UV) radiation received at the Earth's surface. This chapter discusses advances that were made since the previous assessment (World Meteorological Organization (WMO)) to our understanding of UV radiation. The impacts of these changes in UV on the biosphere are not included, because they are discussed in the effects assessment.

Beta HPV38 oncoproteins act with a hit-and-run mechanism in ultraviolet radiation-induced skin carcinogenesis in mice.

PubMed

Viarisio, Daniele; Müller-Decker, Karin; Accardi, Rosita; Robitaille, Alexis; Dürst, Matthias; Beer, Katrin; Jansen, Lars; Flechtenmacher, Christa; Bozza, Matthias; Harbottle, Richard; Voegele, Catherine; Ardin, Maude; Zavadil, Jiri; Caldeira, Sandra; Gissmann, Lutz; Tommasino, Massimo

2018-01-01

Cutaneous beta human papillomavirus (HPV) types are suspected to be involved, together with ultraviolet (UV) radiation, in the development of non-melanoma skin cancer (NMSC). Studies in in vitro and in vivo experimental models have highlighted the transforming properties of beta HPV E6 and E7 oncoproteins. However, epidemiological findings indicate that beta HPV types may be required only at an initial stage of carcinogenesis, and may become dispensable after full establishment of NMSC. Here, we further investigate the potential role of beta HPVs in NMSC using a Cre-loxP-based transgenic (Tg) mouse model that expresses beta HPV38 E6 and E7 oncogenes in the basal layer of the skin epidermis and is highly susceptible to UV-induced carcinogenesis. Using whole-exome sequencing, we show that, in contrast to WT animals, when exposed to chronic UV irradiation K14 HPV38 E6/E7 Tg mice accumulate a large number of UV-induced DNA mutations, which increase proportionally with the severity of the skin lesions. The mutation pattern detected in the Tg skin lesions closely resembles that detected in human NMSC, with the highest mutation rate in p53 and Notch genes. Using the Cre-lox recombination system, we observed that deletion of the viral oncogenes after development of UV-induced skin lesions did not affect the tumour growth. Together, these findings support the concept that beta HPV types act only at an initial stage of carcinogenesis, by potentiating the deleterious effects of UV radiation.

Beta HPV38 oncoproteins act with a hit-and-run mechanism in ultraviolet radiation-induced skin carcinogenesis in mice

PubMed Central

Müller-Decker, Karin; Accardi, Rosita; Flechtenmacher, Christa; Bozza, Matthias; Harbottle, Richard; Voegele, Catherine; Ardin, Maude; Zavadil, Jiri; Gissmann, Lutz

2018-01-01

Cutaneous beta human papillomavirus (HPV) types are suspected to be involved, together with ultraviolet (UV) radiation, in the development of non-melanoma skin cancer (NMSC). Studies in in vitro and in vivo experimental models have highlighted the transforming properties of beta HPV E6 and E7 oncoproteins. However, epidemiological findings indicate that beta HPV types may be required only at an initial stage of carcinogenesis, and may become dispensable after full establishment of NMSC. Here, we further investigate the potential role of beta HPVs in NMSC using a Cre-loxP-based transgenic (Tg) mouse model that expresses beta HPV38 E6 and E7 oncogenes in the basal layer of the skin epidermis and is highly susceptible to UV-induced carcinogenesis. Using whole-exome sequencing, we show that, in contrast to WT animals, when exposed to chronic UV irradiation K14 HPV38 E6/E7 Tg mice accumulate a large number of UV-induced DNA mutations, which increase proportionally with the severity of the skin lesions. The mutation pattern detected in the Tg skin lesions closely resembles that detected in human NMSC, with the highest mutation rate in p53 and Notch genes. Using the Cre-lox recombination system, we observed that deletion of the viral oncogenes after development of UV-induced skin lesions did not affect the tumour growth. Together, these findings support the concept that beta HPV types act only at an initial stage of carcinogenesis, by potentiating the deleterious effects of UV radiation. PMID:29324843

Protection of radiation induced DNA and membrane damages by total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst.

PubMed

Smina, T P; Maurya, D K; Devasagayam, T P A; Janardhanan, K K

2015-05-25

The total triterpenes isolated from the fruiting bodies of Ganoderma lucidum was examined for its potential to prevent γ-radiation induced membrane damage in rat liver mitochondria and microsomes. The effects of total triterpenes on γ-radiation-induced DNA strand breaks in pBR 322 plasmid DNA in vitro and human peripheral blood lymphocytes ex vivo were evaluated. The protective effect of total triterpenes against γ-radiation-induced micronuclei formations in mice bone marrow cells in vivo were also evaluated. The results indicated the significant effectiveness of Ganoderma triterpenes in protecting the DNA and membrane damages consequent to the hazardous effects of radiation. The findings suggest the potential use of Ganoderma triterpenes in radio therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Increased resistance to ionizing and ultraviolet radiation in Escherichia coli JM83 is associated with a chromosomal rearrangement.

PubMed

McLean, K M; Gutman, P D; Minton, K W; Clark, E P

1992-06-01

Cells cope with radiation damage through several mechanisms: (1) increased DNA repair activity, (2) scavenging and inactivation of radiation-induced radical molecules, and (3) entry into a G0-like quiescent state. We have investigated a chromosomal rearrangement to elucidate further the molecular and genetic mechanisms underlying these phenomena. A mutant of Escherichia coli JM83 (phi 80dlacZ delta M15) was isolated that demonstrated significantly increased resistance to both ionizing and ultraviolet radiation. Surviving fractions of mutant and wild-type cells were measured following exposure to standardized doses of radiation. Increased radioresistance was directly related to a chromosomal alteration near the bacteriophage phi 80 attachment site (attB), as initially detected by the LacZ- phenotype of the isolate. Southern hybridization of chromosomal DNA from the mutant and wild-type E. coli JM83 strains indicated that a deletion had occurred. We propose that the deletion near the attB locus produces the radioresistant phenotype of the E. coli JM83 LacZ- mutant, perhaps through the alteration or inactivation of a gene or its controlling element(s).

European Code against Cancer 4th Edition: Ultraviolet radiation and cancer.

PubMed

Greinert, Rüdiger; de Vries, Esther; Erdmann, Friederike; Espina, Carolina; Auvinen, Anssi; Kesminiene, Ausrele; Schüz, Joachim

2015-12-01

Ultraviolet radiation (UVR) is part of the electromagnetic spectrum emitted naturally from the sun or from artificial sources such as tanning devices. Acute skin reactions induced by UVR exposure are erythema (skin reddening), or sunburn, and the acquisition of a suntan triggered by UVR-induced DNA damage. UVR exposure is the main cause of skin cancer, including cutaneous malignant melanoma, basal-cell carcinoma, and squamous-cell carcinoma. Skin cancer is the most common cancer in fair-skinned populations, and its incidence has increased steeply over recent decades. According to estimates for 2012, about 100,000 new cases of cutaneous melanoma and about 22,000 deaths from it occurred in Europe. The main mechanisms by which UVR causes cancer are well understood. Exposure during childhood appears to be particularly harmful. Exposure to UVR is a risk factor modifiable by individuals' behaviour. Excessive exposure from natural sources can be avoided by seeking shade when the sun is strongest, by wearing appropriate clothing, and by appropriately applying sunscreens if direct sunlight is unavoidable. Exposure from artificial sources can be completely avoided by not using sunbeds. Beneficial effects of sun or UVR exposure, such as for vitamin D production, can be fully achieved while still avoiding too much sun exposure and the use of sunbeds. Taking all the scientific evidence together, the recommendation of the 4th edition of the European Code Against Cancer for ultraviolet radiation is: "Avoid too much sun, especially for children. Use sun protection. Do not use sunbeds." Copyright © 2015 International Agency for Research on Cancer. Published by Elsevier Ltd. All rights reserved.

Topically Applied Carvedilol Attenuates Solar Ultraviolet Radiation Induced Skin Carcinogenesis.

PubMed

Huang, Kevin M; Liang, Sherry; Yeung, Steven; Oiyemhonlan, Etuajie; Cleveland, Kristan H; Parsa, Cyrus; Orlando, Robert; Meyskens, Frank L; Andresen, Bradley T; Huang, Ying

2017-10-01

In previous studies, the β-blocker carvedilol inhibited EGF-induced epidermal cell transformation and chemical carcinogen-induced mouse skin hyperplasia. As exposure to ultraviolet (UV) radiation leads to skin cancer, the present study examined whether carvedilol can prevent UV-induced carcinogenesis. Carvedilol absorbs UV like a sunscreen; thus, to separate pharmacological from sunscreen effects, 4-hydroxycarbazole (4-OHC), which absorbs UV to the same degree as carvedilol, served as control. JB6 P + cells, an established epidermal model for studying tumor promotion, were used for evaluating the effect of carvedilol on UV-induced neoplastic transformation. Both carvedilol and 4-OHC (1 μmol/L) blocked transformation induced by chronic UV (15 mJ/cm 2 ) exposure for 8 weeks. However, EGF-mediated transformation was inhibited by only carvedilol but not by 4-OHC. Carvedilol (1 and 5 μmol/L), but not 4-OHC, attenuated UV-induced AP-1 and NF-κB luciferase reporter activity, suggesting a potential anti-inflammatory activity. In a single-dose UV (200 mJ/cm 2 )-induced skin inflammation mouse model, carvedilol (10 μmol/L), applied topically after UV exposure, reduced skin hyperplasia and the levels of cyclobutane pyrimidine dimers, IL1β, IL6, and COX-2 in skin. In SKH-1 mice exposed to gradually increasing levels of UV (50-150 mJ/cm 2 ) three times a week for 25 weeks, topical administration of carvedilol (10 μmol/L) after UV exposure increased tumor latency compared with control (week 18 vs. 15), decreased incidence and multiplicity of squamous cell carcinomas, while 4-OHC had no effect. These data suggest that carvedilol has a novel chemopreventive activity and topical carvedilol following UV exposure may be repurposed for preventing skin inflammation and cancer. Cancer Prev Res; 10(10); 598-606. ©2017 AACR . ©2017 American Association for Cancer Research.

CDK1 enhances mitochondrial bioenergetics for radiation-induced DNA repair

DOE PAGES

Qin, Lili; Fan, Ming; Candas, Demet; ...

2015-12-06

Nuclear DNA repair capacity is a critical determinant of cell fate under genotoxic stress conditions. DNA repair is a well-defined energy-consuming process. However, it is unclear how DNA repair is fueled and whether mitochondrial energy production contributes to nuclear DNA repair. Here, we report a dynamic enhancement of oxygen consumption and mitochondrial ATP generation in irradiated normal cells, paralleled with increased mitochondrial relocation of the cell-cycle kinase CDK1 and nuclear DNA repair. The basal and radiation-induced mitochondrial ATP generation is reduced significantly in cells harboring CDK1 phosphorylation-deficient mutant complex I subunits. Similarly, mitochondrial ATP generation and nuclear DNA repair aremore » also compromised severely in cells harboring mitochondrially targeted, kinase-deficient CDK1. These findings demonstrate a mechanism governing the communication between mitochondria and the nucleus by which CDK1 boosts mitochondrial bioenergetics to meet the increased cellular fuel demand for DNA repair and cell survival under genotoxic stress conditions.« less

Experimental Determination of Ultraviolet Radiation Protection of Common Materials

ERIC Educational Resources Information Center

Tavares, Susana C. A.; da Silva, Joaquim C. G. Esteves; Paiva, Joao

2007-01-01

Aiming at a better understanding of the problems associated with the depletion of the ozone layer, we propose several experiments to be performed by students of different levels: secondary and first-year undergraduate students. The oxidation of iodide induced by ultraviolet (UV) radiation, generated by a mercury lamp, is used as an indicator for…

Molecular and sensory mechanisms to mitigate sunlight-induced DNA damage in treefrog tadpoles.

PubMed

Schuch, André P; Lipinski, Victor M; Santos, Mauricio B; Santos, Caroline P; Jardim, Sinara S; Cechin, Sonia Z; Loreto, Elgion L S

2015-10-01

The increased incidence of solar ultraviolet B (UVB) radiation has been proposed as an environmental stressor, which may help to explain the enigmatic decline of amphibian populations worldwide. Despite growing knowledge regarding the UV-induced biological effects in several amphibian models, little is known about the efficacy of DNA repair pathways. In addition, little attention has been given to the interplay between these molecular mechanisms with other physiological strategies that avoid the damage induced by sunlight. Here, DNA lesions induced by environmental doses of solar UVB and UVA radiation were detected in genomic DNA samples of treefrog tadpoles (Hypsiboas pulchellus) and their DNA repair activity was evaluated. These data were complemented by monitoring the induction of apoptosis in blood cells and tadpole survival. Furthermore, the tadpoles' ability to perceive and escape from UV wavelengths was evaluated as an additional strategy of photoprotection. The results show that tadpoles are very sensitive to UVB light, which could be explained by the slow DNA repair rates for both cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6,4) pyrimidone photoproducts (6,4PPs). However, they were resistant to UVA, probably as a result of the activation of photolyases during UVA irradiation. Surprisingly, a sensory mechanism that triggers their escape from UVB and UVA light avoids the generation of DNA damage and helps to maintain the genomic integrity. This work demonstrates the genotoxic impact of both UVB and UVA radiation on tadpoles and emphasizes the importance of the interplay between molecular and sensory mechanisms to minimize the damage caused by sunlight. © 2015. Published by The Company of Biologists Ltd.

Ultraviolet Absorption Induces Hydrogen-Atom Transfer in G⋅C Watson-Crick DNA Base Pairs in Solution.

PubMed

Röttger, Katharina; Marroux, Hugo J B; Grubb, Michael P; Coulter, Philip M; Böhnke, Hendrik; Henderson, Alexander S; Galan, M Carmen; Temps, Friedrich; Orr-Ewing, Andrew J; Roberts, Gareth M

2015-12-01

Ultrafast deactivation pathways bestow photostability on nucleobases and hence preserve the structural integrity of DNA following absorption of ultraviolet (UV) radiation. One controversial recovery mechanism proposed to account for this photostability involves electron-driven proton transfer (EDPT) in Watson-Crick base pairs. The first direct observation is reported of the EDPT process after UV excitation of individual guanine-cytosine (G⋅C) Watson-Crick base pairs by ultrafast time-resolved UV/visible and mid-infrared spectroscopy. The formation of an intermediate biradical species (G[-H]⋅C[+H]) with a lifetime of 2.9 ps was tracked. The majority of these biradicals return to the original G⋅C Watson-Crick pairs, but up to 10% of the initially excited molecules instead form a stable photoproduct G*⋅C* that has undergone double hydrogen-atom transfer. The observation of these sequential EDPT mechanisms across intermolecular hydrogen bonds confirms an important and long debated pathway for the deactivation of photoexcited base pairs, with possible implications for the UV photochemistry of DNA. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inhibition of gamma-radiation induced DNA damage in plasmid pBR322 by TMG, a water-soluble derivative of vitamin E.

PubMed

Rajagopalan, Rema; Wani, Khalida; Huilgol, Nagaraj G; Kagiya, Tsutomu V; Nair, Cherupally K Krishnan

2002-06-01

Alpha-tocopherol monoglucoside (TMG), a water-soluble derivative of alpha-tocopherol, has been examined for its ability to protect DNA against radiation-induced strand breaks. Gamma radiation, up to a dose of 6 Gy (dose rate, 0.7 Gy/minute), induced a dose-dependent increase in single strand breaks (SSBs) in plasmid pBR322 DNA. TMG inhibited the formation of gamma-radiation induced DNA single strand breaks (SSBs) in a concentration-dependent manner; 500 microM of TMG protected the single strand breaks completely. It also protected thymine glycol formation induced by gamma-radiation in a dose-dependent manner, based on an estimation of thymine glycol by HPLC.

Photokeratitis induced by ultraviolet radiation in travelers: A major health problem

PubMed Central

Izadi, M; Jonaidi-Jafari, N; Pourazizi, M; Alemzadeh-Ansari, MH; Hoseinpourfard, MJ

2018-01-01

Ultraviolet (UV) irradiation is one of the several environmental hazards that may cause inflammatory reactions in ocular tissues, especially the cornea. One of the important factors that affect how much ultraviolet radiation (UVR) humans are exposed to is travel. Hence, traveling is considered to include a more acute UVR effect, and ophthalmologists frequently evaluate and manage the ocular manifestations of UV irradiation, including UV-induced keratitis. The purpose of this paper is to provide an evidence-based analysis of the clinical effect of UVR in ocular tissues. An extensive review of English literature was performed to gather all available articles from the National Library of Medicine PubMed database of the National Institute of Health, the Ovid MEDLINE database, Scopus, and ScienceDirect that had studied the effect of UVR on the eye and its complications, between January 1970 and June 2014. The results show that UVR at 300 nm causes apoptosis in all three layers of the cornea and induces keratitis. Apoptosis in all layers of the cornea occurs 5 h after exposure. The effect of UVR intensity on the eye can be linked to numerous factors, including solar elevation, time of day, season, hemisphere, clouds and haze, atmospheric scattering, atmospheric ozone, latitude, altitude, longitudinal changes, climate, ground reflection, and geographic directions. The most important factor affecting UVR reaching the earth's surface is solar elevation. Currently, people do not have great concern over eye protection. The methods of protection against UVR include avoiding direct sunlight exposure, using UVR-blocking eyewear (sunglasses or contact lenses), and wearing hats. Hence, by identifying UVR intensity factors, eye protection factors, and public education, especially in travelers, methods for safe traveling can be identified. PMID:29067921

Photokeratitis induced by ultraviolet radiation in travelers: A major health problem.

PubMed

Izadi, M; Jonaidi-Jafari, N; Pourazizi, M; Alemzadeh-Ansari, M H; Hoseinpourfard, M J

2018-01-01

Ultraviolet (UV) irradiation is one of the several environmental hazards that may cause inflammatory reactions in ocular tissues, especially the cornea. One of the important factors that affect how much ultraviolet radiation (UVR) humans are exposed to is travel. Hence, traveling is considered to include a more acute UVR effect, and ophthalmologists frequently evaluate and manage the ocular manifestations of UV irradiation, including UV-induced keratitis. The purpose of this paper is to provide an evidence-based analysis of the clinical effect of UVR in ocular tissues. An extensive review of English literature was performed to gather all available articles from the National Library of Medicine PubMed database of the National Institute of Health, the Ovid MEDLINE database, Scopus, and ScienceDirect that had studied the effect of UVR on the eye and its complications, between January 1970 and June 2014. The results show that UVR at 300 nm causes apoptosis in all three layers of the cornea and induces keratitis. Apoptosis in all layers of the cornea occurs 5 h after exposure. The effect of UVR intensity on the eye can be linked to numerous factors, including solar elevation, time of day, season, hemisphere, clouds and haze, atmospheric scattering, atmospheric ozone, latitude, altitude, longitudinal changes, climate, ground reflection, and geographic directions. The most important factor affecting UVR reaching the earth's surface is solar elevation. Currently, people do not have great concern over eye protection. The methods of protection against UVR include avoiding direct sunlight exposure, using UVR-blocking eyewear (sunglasses or contact lenses), and wearing hats. Hence, by identifying UVR intensity factors, eye protection factors, and public education, especially in travelers, methods for safe traveling can be identified.

Photosensitized UVA-Induced Cross-Linking between Human DNA Repair and Replication Proteins and DNA Revealed by Proteomic Analysis

PubMed Central

2016-01-01

Long wavelength ultraviolet radiation (UVA, 320–400 nm) interacts with chromophores present in human cells to induce reactive oxygen species (ROS) that damage both DNA and proteins. ROS levels are amplified, and the damaging effects of UVA are exacerbated if the cells are irradiated in the presence of UVA photosensitizers such as 6-thioguanine (6-TG), a strong UVA chromophore that is extensively incorporated into the DNA of dividing cells, or the fluoroquinolone antibiotic ciprofloxacin. Both DNA-embedded 6-TG and ciprofloxacin combine synergistically with UVA to generate high levels of ROS. Importantly, the extensive protein damage induced by these photosensitizer+UVA combinations inhibits DNA repair. DNA is maintained in intimate contact with the proteins that effect its replication, transcription, and repair, and DNA–protein cross-links (DPCs) are a recognized reaction product of ROS. Cross-linking of DNA metabolizing proteins would compromise these processes by introducing physical blocks and by depleting active proteins. We describe a sensitive and statistically rigorous method to analyze DPCs in cultured human cells. Application of this proteomics-based analysis to cells treated with 6-TG+UVA and ciprofloxacin+UVA identified proteins involved in DNA repair, replication, and gene expression among those most vulnerable to cross-linking under oxidative conditions. PMID:27654267

Radiation-Induced Chromosomal Aberrations and Immunotherapy: Micronuclei, Cytosolic DNA, and Interferon-Production Pathway.

PubMed

Durante, Marco; Formenti, Silvia C

2018-01-01

Radiation-induced chromosomal aberrations represent an early marker of late effects, including cell killing and transformation. The measurement of cytogenetic damage in tissues, generally in blood lymphocytes, from patients treated with radiotherapy has been studied for many years to predict individual sensitivity and late morbidity. Acentric fragments are lost during mitosis and create micronuclei (MN), which are well correlated to cell killing. Immunotherapy is rapidly becoming a most promising new strategy for metastatic tumors, and combination with radiotherapy is explored in several pre-clinical studies and clinical trials. Recent evidence has shown that the presence of cytosolic DNA activates immune response via the cyclic GMP-AMP synthase/stimulator of interferon genes pathway, which induces type I interferon transcription. Cytosolic DNA can be found after exposure to ionizing radiation either as MN or as small fragments leaking through nuclear envelope ruptures. The study of the dependence of cytosolic DNA and MN on dose and radiation quality can guide the optimal combination of radiotherapy and immunotherapy. The role of densely ionizing charged particles is under active investigation to define their impact on the activation of the interferon pathway.

Ocean acidification alters the photosynthetic responses of a coccolithophorid to fluctuating ultraviolet and visible radiation.

PubMed

Jin, Peng; Gao, Kunshan; Villafañe, Virginia E; Campbell, Douglas A; Helbling, E Walter

2013-08-01

Mixing of seawater subjects phytoplankton to fluctuations in photosynthetically active radiation (400-700 nm) and ultraviolet radiation (UVR; 280-400 nm). These irradiance fluctuations are now superimposed upon ocean acidification and thinning of the upper mixing layer through stratification, which alters mixing regimes. Therefore, we examined the photosynthetic carbon fixation and photochemical performance of a coccolithophore, Gephyrocapsa oceanica, grown under high, future (1,000 μatm) and low, current (390 μatm) CO₂ levels, under regimes of fluctuating irradiances with or without UVR. Under both CO₂ levels, fluctuating irradiances, as compared with constant irradiance, led to lower nonphotochemical quenching and less UVR-induced inhibition of carbon fixation and photosystem II electron transport. The cells grown under high CO₂ showed a lower photosynthetic carbon fixation rate but lower nonphotochemical quenching and less ultraviolet B (280-315 nm)-induced inhibition. Ultraviolet A (315-400 nm) led to less enhancement of the photosynthetic carbon fixation in the high-CO₂-grown cells under fluctuating irradiance. Our data suggest that ocean acidification and fast mixing or fluctuation of solar radiation will act synergistically to lower carbon fixation by G. oceanica, although ocean acidification may decrease ultraviolet B-related photochemical inhibition.

Fungal beta glucan protects radiation induced DNA damage in human lymphocytes.

PubMed

Pillai, Thulasi G; Maurya, Dharmendra K; Salvi, Veena P; Janardhanan, Krishnankutty K; Nair, Cherupally K K

2014-02-01

Ganoderma lucidum (Ling Zhi), a basidiomycete white rot macrofungus has been used extensively for therapeutic use in China, Japan, Korea and other Asian countries for 2,000 years. The present study is an attempt to investigate its DNA protecting property in human lymphocytes. Beta glucan (BG) was isolated by standard procedure and the structure and composition were studied by infrared radiation (IR) and nuclear magnetic resonance (NMR) spectroscopy, gel filtration chromatography and paper chromatography. The radioprotective properties of BG isolated from the macro fungi Ganoderma lucidum was assessed by single cell gel electrophoresis (comet assay). Human lymphocytes were exposed to 0, 1, 2 and 4 Gy gamma radiation in the presence and absence of BG. The comet parameters were reduced by BG. The results indicate that the BG of G. lucidum possessed significant radioprotective activity with DNA repairing ability and antioxidant activity as the suggestive mechanism. The findings suggest the potential use of this mushroom for the prevention of radiation induced cellular damages.

Evidence that Singlet Oxygen-induced Human T Helper Cell Apoptosis Is the Basic Mechanism of Ultraviolet-A Radiation Phototherapy

PubMed Central

Morita, Akimichi; Werfel, Thomas; Stege, Helger; Ahrens, Constanze; Karmann, Karin; Grewe, Markus; Grether-Beck, Susanne; Ruzicka, Thomas; Kapp, Alexander; Klotz, Lars-Oliver; Sies, Helmut; Krutmann, Jean

1997-01-01

Ultraviolet A (UVA) irradiation is effectively used to treat patients with atopic dermatitis and other T cell mediated, inflammatory skin diseases. In the present study, successful phototherapy of atopic dermatitis was found to result from UVA radiation-induced apoptosis in skin-infiltrating T helper cells, leading to T cell depletion from eczematous skin. In vitro, UVA radiation-induced human T helper cell apoptosis was mediated through the FAS/FAS-ligand system, which was activated in irradiated T cells as a consequence of singlet oxygen generation. These studies demonstrate that singlet oxygen is a potent trigger for the induction of human T cell apoptosis. They also identify singlet oxygen generation as a fundamental mechanism of action operative in phototherapy. PMID:9362536

[Blocking 1800 MHz mobile phone radiation-induced reactive oxygen species production and DNA damage in lens epithelial cells by noise magnetic fields].

PubMed

Wu, Wei; Yao, Ke; Wang, Kai-jun; Lu, De-qiang; He, Ji-liang; Xu, Li-hong; Sun, Wen-jun

2008-01-01

To investigate whether the exposure to the electromagnetic noise can block reactive oxygen species (ROS) production and DNA damage of lens epithelial cells induced by 1800 MHz mobile phone radiation. The DCFH-DA method and comet assay were used respectively to detect the intracellular ROS and DNA damage of cultured human lens epithelial cells induced by 4 W/kg 1800 MHz mobile phone radiation or/and 2 muT electromagnetic noise for 24 h intermittently. 1800 MHz mobile phone radiation at 4 W/kg for 24 h increased intracellular ROS and DNA damage significantly (P<0.05). However, the ROS level and DNA damage of mobile phone radiation plus noise group were not significant enhanced (P>0.05) as compared to sham exposure group. Electromagnetic noise can block intracellular ROS production and DNA damage of human lens epithelial cells induced by 1800 MHz mobile phone radiation.

Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Costes, Sylvain V; Chiolo, Irene; Pluth, Janice M.

2009-09-15

DNA damage sensing proteins have been shown to localize to the sites of DSB within seconds to minutes following ionizing radiation (IR) exposure, resulting in the formation of microscopically visible nuclear domains referred to as radiation-induced foci (RIF). This review characterizes the spatio-temporal properties of RIF at physiological doses, minutes to hours following exposure to ionizing radiation, and it proposes a model describing RIF formation and resolution as a function of radiation quality and nuclear densities. Discussion is limited to RIF formed by three interrelated proteins ATM (Ataxia telangiectasia mutated), 53BP1 (p53 binding protein 1) and ?H2AX (phosphorylated variant histonemore » H2AX). Early post-IR, we propose that RIF mark chromatin reorganization, leading to a local nuclear scaffold rigid enough to keep broken DNA from diffusing away, but open enough to allow the repair machinery. We review data indicating clear kinetic and physical differences between RIF emerging from dense and uncondensed regions of the nucleus. At later time post-IR, we propose that persistent RIF observed days following exposure to ionizing radiation are nuclear ?scars? marking permanent disruption of the chromatin architecture. When DNA damage is resolved, such chromatin modifications should not necessarily lead to growth arrest and it has been shown that persistent RIF can replicate during mitosis. Thus, heritable persistent RIF spanning over tens of Mbp may affect the transcriptome of a large progeny of cells. This opens the door for a non DNA mutation-based mechanism of radiation-induced phenotypes.« less

Silver nanoparticles protect human keratinocytes against UVB radiation-induced DNA damage and apoptosis: potential for prevention of skin carcinogenesis

PubMed Central

Arora, Sumit; Tyagi, Nikhil; Bhardwaj, Arun; Rusu, Lilia; Palanki, Rohan; Vig, Komal; Singh, Shree R.; Singh, Ajay P.; Palanki, Srinivas; Miller, Michael E.; Carter, James E.; Singh, Seema

2015-01-01

Ultraviolet (UV)-B radiation from the sun is an established etiological cause of skin cancer, which afflicts more than a million lives each year in the United States alone. Here, we tested the chemopreventive efficacy of silver-nanoparticles (AgNPs) against UVB-irradiation-induced DNA damage and apoptosis in human immortalized keratinocytes (HaCaT). AgNPs were synthesized by reduction-chemistry and characterized for their physicochemical properties. AgNPs were well tolerated by HaCaT cells and their pretreatment protected them from UVB-irradiation-induced apoptosis along with significant reduction in cyclobutane-pyrimidine-dimer formation. Moreover, AgNPs pre-treatment led to G1-phase cell-cycle arrest in UVB-irradiated HaCaT cells. AgNPs were efficiently internalized in UVB-irradiated cells and localized into cytoplasmic and nuclear compartments. Furthermore, we observed an altered expression of various genes involved in cell-cycle, apoptosis and nucleotide-excision repair in HaCaT cells treated with AgNPs prior to UVB-irradiation. Together, these findings provide support for potential utility of AgNPs as novel chemopreventive agents against UVB-irradiation-induced skin carcinogenesis. PMID:25804413

Occupational skin cancer induced by ultraviolet radiation and its prevention.

PubMed

Diepgen, T L; Fartasch, M; Drexler, H; Schmitt, J

2012-08-01

Skin cancer is by far the most common kind of cancer diagnosed in many western countries and ultraviolet radiation is the most important risk factor for cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Although employees at several workplaces are exposed to increased levels of UV radiation, skin cancer due to long-term intense occupational exposure to UV radiation is often not considered as occupational disease. The actually available evidence in the epidemiological literature clearly indicates that occupational UV radiation exposure is a substantial and robust risk factor for the development of cutaneous SCC and also clearly shows a significant risk for developing BCC. There is enough scientific evidence that outdoor workers have an increased risk of developing work-related occupational skin cancer due to natural UV radiation exposure and adequate prevention strategies must be implemented. The three measures which are successful and of particular importance in the prevention of nonmelanoma skin cancer in outdoor workers are changes in behaviour regarding awareness of health and disease resulting from exposure to natural UV radiation, protection from direct UV radiation by wearing suitable clothing, and regular and correct use of appropriate sunscreens. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

Animal model for evaluation of topical photoprotection against ultraviolet A (320-380 nm) radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chew, S.; DeLeo, V.A.; Harber, L.C.

Recent studies reporting UVA (ultraviolet A radiation 320-380 nm) as an integral part of the cumulative sun-induced damage in human skin have prompted an interest in developing effective UVA photoprotective agents. The development of such compounds has been impeded by the absence of a clinically relevant animal model for evaluating their efficacy. This report describes the development and use of such a laboratory animal system. Selected concentrations of oxybenzone (2-hydroxy-4-methoxybenzophenone) in vehicle (0.1% to 6%) or vehicle alone were applied to the depilated dorsal skin of 30 Hartley strain female albino guinea pigs. The skin was irradiated with solar simulatedmore » UVA from a xenon light source. Acute radiation-induced damage was assayed by erythema grading and inhibition of (/sup 3/H)thymidine incorporation into epidermal DNA. Data from erythema grading studies indicated that a significant degree of photoprotection was achieved with 6%, 3%, and 1% solutions of benzophenone compared with the control vehicle; the 6% solution was significantly more photoprotective than the 3% and 1% solutions. A 6% solution afforded significant photoprotection when assayed by (/sup 3/H)thymidine incorporation.« less

Adrenergic Receptor Stimulation Prevents Radiation-Induced DNA Strand Breaks, Apoptosis and Gene Expression in Simulated Microgravity

NASA Technical Reports Server (NTRS)

Moreno-Villanueva, Maria; Krieger, Stephanie; Feiveson, Alan; Kovach, Annie Marie; Buerkle, Alexander; Wu, Honglu

2017-01-01

Under Earth gravity conditions cellular damage can be counteracted by activation of the physiological defense mechanisms or through medical interventions. The mode of action of both, physiological response and medical interventions can be affected by microgravity leading to failure in repairing the damage. There are many studies reporting the effects of microgravity and/or radiation on cellular functions. However, little is known about the synergistic effects on cellular response to radiation when other endogenous cellular stress-response pathways are previously activated. Here, we investigated whether previous stimulation of the adrenergic receptor, which modulates immune response, affects radiation-induced apoptosis in immune cells under simulated microgravity conditions. Peripheral blood mononuclear cells (PBMCs) were stimulated with isoproterenol (a sympathomimetic drug) and exposed to 0.8 or 2Gy gamma-radiation in simulated microgravity versus Earth gravity. Expression of genes involved in adrenergic receptor pathways, DNA repair and apoptosis as well as the number of apoptotic cells and DNA strand breaks were determined. Our results showed that, under simulated microgravity conditions, previous treatment with isoproterenol prevented radiation-induced i) gene down regulation, ii) DNA strand breaks formation and iii) apoptosis induction. Interestedly, we found a radiation-induced increase of adrenergic receptor gene expression, which was also abolished in simulated microgravity. Understanding the mechanisms of isoproterenol-mediated radioprotection in simulated microgravity can help to develop countermeasures for space-associated health risks as well as radio-sensitizers for cancer therapy.

Fungal beta glucan protects radiation induced DNA damage in human lymphocytes

PubMed Central

Maurya, Dharmendra K.; Salvi, Veena P.; Janardhanan, Krishnankutty K; Nair, Cherupally K. K.

2014-01-01

Background Ganoderma lucidum (Ling Zhi), a basidiomycete white rot macrofungus has been used extensively for therapeutic use in China, Japan, Korea and other Asian countries for 2,000 years. The present study is an attempt to investigate its DNA protecting property in human lymphocytes. Materials and methods Beta glucan (BG) was isolated by standard procedure and the structure and composition were studied by infrared radiation (IR) and nuclear magnetic resonance (NMR) spectroscopy, gel filtration chromatography and paper chromatography. The radioprotective properties of BG isolated from the macro fungi Ganoderma lucidum was assessed by single cell gel electrophoresis (comet assay). Human lymphocytes were exposed to 0, 1, 2 and 4 Gy gamma radiation in the presence and absence of BG. Results The comet parameters were reduced by BG. The results indicate that the BG of G. lucidum possessed significant radioprotective activity with DNA repairing ability and antioxidant activity as the suggestive mechanism. Conclusions The findings suggest the potential use of this mushroom for the prevention of radiation induced cellular damages. PMID:25332989

Dichromatic laser radiation effects on DNA of Escherichia coli and plasmids

NASA Astrophysics Data System (ADS)

Martins, W. A.; Polignano, G. A. C.; Guimarães, O. R.; Geller, M.; Paoli, F.; Fonseca, A. S.

2015-04-01

Dichromatic and consecutive laser radiations have attracted increased attention for clinical applications as offering new tools for the treatment of dysfunctional tissues in situations where monochromatic radiation is not effective. This work evaluated the survival, filamentation and morphology of Escherichia coli cells, and the induction of DNA lesions, in plasmid DNA exposed to low-intensity consecutive dichromatic laser radiation. Exponential and stationary wild type and formamidopyrimidine DNA glycosylase/MutM protein deficient E. coli cultures were exposed to consecutive low-intensity dichromatic laser radiation (infrared laser immediately after red laser) to study the survival, filamentation and morphology of bacterial cells. Plasmid DNA samples were exposed to dichromatic radiation to study DNA lesions by electrophoretic profile. Dichromatic laser radiation affects the survival, filamentation and morphology of E. coli cultures depending on the growth phase and the functional repair mechanism of oxidizing lesions in DNA, but does not induce single/double strands breaks or alkali-labile DNA lesions. Results show that low-intensity consecutive dichromatic laser radiation induces biological effects that differ from those induced by monochromatic laser radiation, suggesting that other therapeutic effects could be obtained using dichromatic radiation.

Significant Suppression of CT Radiation-Induced DNA Damage in Normal Human Cells by the PrC-210 Radioprotector.

PubMed

Jermusek, Frank; Benedict, Chelsea; Dreischmeier, Emma; Brand, Michael; Uder, Michael; Jeffery, Justin J; Ranallo, Frank N; Fahl, William E

2018-05-21

While computed tomography (CT) is now commonly used and considered to be clinically valuable, significant DNA double-strand breaks (γ-H2AX foci) in white blood cells from adult and pediatric CT patients have been frequently reported. In this study to determine whether γ-H2AX foci and X-ray-induced naked DNA damage are suppressed by administration of the PrC-210 radioprotector, human blood samples were irradiated in a CT scanner at 50-150 mGy with or without PrC-210, and γ-H2AX foci were scored. X-ray-induced naked DNA damage was also studied, and the DNA protective efficacy of PrC-210 was compared against 12 other common "antioxidants." PrC-210 reduced CT radiation-induced γ-H2AX foci in white blood cells to near background ( P < 0.0001) at radiation doses of 50-150 mGy. PrC-210 was most effective among the 13 "antioxidants" in reducing naked DNA X-ray damage, and its addition at 30 s before an • OH pulse reduced to background the • OH insult that otherwise induced >95% DNA damage. A systemic PrC-210 dose known to confer 100% survival in irradiated mice had no discernible effect on micro-CT image signal-to-noise ratio and CT image integrity. PrC-210 suppressed DNA damage to background or near background in each of these assay systems, thus supporting its development as a radioprotector for humans in multiple radiation exposure settings.

[Ultraviolet radiation-induced apoptosis in human lens epithelial cells and its effect on Bcl-2 and Bax].

PubMed

Jia, Songbai; Shi, Jingming; Chen, Xuan; Tang, Luosheng

2012-07-01

To explore the apoptosis-inducing effect of ultraviolet(UV) radiation on human lens epithelial cells (HLEC), with particular focus on changes in Bcl-2 or Bax expression as possible mechanisms. All experimental groups were exposed to the same UV light source. HLEC were divided into 6 groups according to duration of UV radiation : 0 min group (control group), 5 min group, 10 min group,15 min group, and 30 min group. Analysis on apoptosis of HLEC was performed by flow cytometry analysis (FCA, Annexin V + PI staining). Changes of Bax and Bcl-2 expression in HLEC were detected by hybridization in situ. Apoptosis in HLEC increased with UV exposure time. The expression level of Bax mRNA was increased with the increase of UV exposure time, whereas the expression level of Bcl-2 mRNA decreased with the increase of UV exposure time. The proportion of apoptotic cells was negatively correlated with ratio of Bcl-2/Bax (r=-0.874, P<0.05). UA radiation can induce apoptosis of HLEC in vitro. Bcl-2 and Bax genes may play an important role in regulating this apoptotic process.

Psoriasis and ultraviolet radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farber, E.M.; Nall, L.

1993-09-01

Prevention and detection screening programs as a public health service in curtailing the ever-increasing incidence of all forms of skin cancer are reviewed. The effect of solar and artificial ultraviolet radiation on the general population and persons with psoriasis is examined. 54 refs.

Investigations of antioxidant-mediated protection and mitigation of radiation-induced DNA damage and lipid peroxidation in murine skin.

PubMed

Jelveh, Salomeh; Kaspler, Pavel; Bhogal, Nirmal; Mahmood, Javed; Lindsay, Patricia E; Okunieff, Paul; Doctrow, Susan R; Bristow, Robert G; Hill, Richard P

2013-08-01

Radioprotection and mitigation effects of the antioxidants, Eukarion (EUK)-207, curcumin, and the curcumin analogs D12 and D68, on radiation-induced DNA damage or lipid peroxidation in murine skin were investigated. These antioxidants were studied because they have been previously reported to protect or mitigate against radiation-induced skin reactions. DNA damage was assessed using two different assays. A cytokinesis-blocked micronucleus (MN) assay was performed on primary skin fibroblasts harvested from the skin of C3H/HeJ male mice 1 day, 1 week and 4 weeks after 5 Gy or 10 Gy irradiation. Local skin or whole body irradiation (100 kVp X-rays or caesium (Cs)-137 γ-rays respectively) was performed. DNA damage was further quantified in keratinocytes by immunofluorescence staining of γ-histone 2AX (γ-H2AX) foci in formalin-fixed skin harvested 1 hour or 1 day post-whole body irradiation. Radiation-induced lipid peroxidation in the skin was investigated at the same time points as the MN assay by measuring malondialdehyde (MDA) with a Thiobarbituric acid reactive substances (TBARS) assay. None of the studied antioxidants showed significant mitigation of skin DNA damage induced by local irradiation. However, when EUK-207 or curcumin were delivered before irradiation they provided some protection against DNA damage. In contrast, all the studied antioxidants demonstrated significant mitigating and protecting effects on radiation-induced lipid peroxidation at one or more of the three time points after local skin irradiation. Our results show no evidence for mitigation of DNA damage by the antioxidants studied in contrast to mitigation of lipid peroxidation. Since these agents have been reported to mitigate skin reactions following irradiation, the data suggest that changes in lipid peroxidation levels in skin may reflect developing skin reactions better than residual post-irradiation DNA damage in skin cells. Further direct comparison studies are required to confirm

Delayed repair of radiation induced clustered DNA damage: Friend or foe?

PubMed Central

Eccles, Laura J.; O’Neill, Peter; Lomax, Martine E.

2011-01-01

A signature of ionizing radiation exposure is the induction of DNA clustered damaged sites, defined as two or more lesions within one to two helical turns of DNA by passage of a single radiation track. Clustered damage is made up of double strand breaks (DSB) with associated base lesions or abasic (AP) sites, and non-DSB clusters comprised of base lesions, AP sites and single strand breaks. This review will concentrate on the experimental findings of the processing of non-DSB clustered damaged sites. It has been shown that non-DSB clustered damaged sites compromise the base excision repair pathway leading to the lifetime extension of the lesions within the cluster, compared to isolated lesions, thus the likelihood that the lesions persist to replication and induce mutation is increased. In addition certain non-DSB clustered damaged sites are processed within the cell to form additional DSB. The use of E. coli to demonstrate that clustering of DNA lesions is the major cause of the detrimental consequences of ionizing radiation is also discussed. The delayed repair of non-DSB clustered damaged sites in humans can be seen as a “friend”, leading to cell killing in tumour cells or as a “foe”, resulting in the formation of mutations and genetic instability in normal tissue. PMID:21130102

Action spectrum and mechanisms of UV radiation-induced injury in lupus erythematosus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kochevar, I.E.

1985-07-01

Photosensitivity associated with lupus erythematosus (LE) is well established. The photobiologic basis for this abnormal response to ultraviolet radiation, however, has not been determined. This paper summarizes the criteria for elucidating possible photobiologic mechanisms and reviews the literature relevant to the mechanism of photosensitivity in LE. In patients with LE, photosensitivity to wavelengths shorter than 320 nm has been demonstrated; wavelengths longer than 320 nm have not been adequately evaluated. DNA is a possible chromophore for photosensitivity below 320 nm. UV irradiation of skin produces thymine photodimers in DNA. UV-irradiated DNA is more antigenic than native DNA and the antigenicitymore » of UV-irradiated DNA has been proposed, but not proven, to be involved in the development of clinical lesions. UV irradiation of mice previously injected with anti-UV-DNA antibodies produces Ig deposition and complement fixation that appears to be similar to the changes seen in lupus lesions. Antibodies to UV-irradiated DNA occur in the serum of LE patients although a correlation between antibody titers and photosensitivity was not observed. Defective repair of UV-induced DNA damage does not appear to be a mechanism for the photosensitivity in LE. Other mechanisms must also be considered. The chromophore for photosensitivity induced by wavelengths longer than 320 nm has not been investigated in vivo. In vitro studies indicate that 360-400 nm radiation activates a photosensitizing compound in the lymphocytes and serum of LE patients and causes chromosomal aberrations and cell death. The mechanism appears to involve superoxide anion.« less

ULTRAVIOLET RADIATION DOWN-REGULATES ALLERGY IN BALB/C MICE

EPA Science Inventory

ULTRAVIOLET RADIATION SUPPRESSES ALLERGY IN BALB/C MICE
Marsha D.W. Ward+ *, Denise M. Sailstad+, Debora L. Andrews, Elizabeth H. Boykin, and MaryJane K. Selgrade

ABSTRACT
The immunosuppressive effects of exposure to ultraviolet radiation (UVR) are well known and the...

Measurement of changes in impedance of DNA nanowires due to radiation induced structural damage. A novel approach for a DNA-based radiosensitive device

NASA Astrophysics Data System (ADS)

Heimbach, Florian; Arndt, Alexander; Nettelbeck, Heidi; Langner, Frank; Giesen, Ulrich; Rabus, Hans; Sellner, Stefan; Toppari, Jussi; Shen, Boxuan; Baek, Woon Yong

2017-08-01

The ability of DNA to conduct electric current has been the topic of numerous investigations over the past few decades. Those investigations indicate that this ability is dependent on the molecular structure of the DNA. Radiation-induced damages, which lead to an alteration of the molecular structure, should therefore change the electrical impedance of a DNA molecule. In this paper, the damage due to ionising radiation is shown to have a direct effect on the electrical transport properties of DNA. Impedance measurements of DNA samples were carried out by an AC impedance spectrometer before, during and after irradiation. The samples comprised of DNA segments, which were immobilized between gold electrodes with a gap of 12 μm. The impedance of all DNA samples exhibited rising capacitive behaviour with increasing absorbed dose.

Synthesis of Deoxyribonucleic Acid After Ultraviolet Irradiation of Sensitive and Resistant Haemophilus influenzae

PubMed Central

Modak, Sohan P.; Setlow, Jane K.

1969-01-01

Synthesis of deoxyribonucleic acid (DNA) has been measured as a function of ultraviolet (UV) radiation dose in wild-type and seven UV-sensitive strains of Haemophilus influenzae. At the UV doses used, all strains were able to resume DNA synthesis, even those which are unable to excise pyrimidine dimers from their DNA. These excisionless strains showed longer UV-induced delays in DNA synthesis than all but one of the other strains. The longest delay was shown by DB117, a strain which can excise dimers but which is recombination deficient and unable to rejoin X ray-induced single-strand breaks. All strains showed a progressive decrease in sensitivity as they approached the stationary phase. PMID:5305934

Radiation-induced genomic instability

NASA Technical Reports Server (NTRS)

Kronenberg, A.

1994-01-01

Quantitative assessment of the heritable somatic effects of ionizing radiation exposures has relied upon the assumption that radiation-induced lesions were 'fixed' in the DNA prior to the first postirradiation mitosis. Lesion conversion was thought to occur during the initial round of DNA replication or as a consequence of error-prone enzymatic processing of lesions. The standard experimental protocols for the assessment of a variety of radiation-induced endpoints (cell death, specific locus mutations, neoplastic transformation and chromosome aberrations) evaluate these various endpoints at a single snapshot in time. In contrast with the aforementioned approaches, some studies have specifically assessed radiation effects as a function of time following exposure. Evidence has accumulated in support of the hypothesis that radiation exposure induces a persistent destabilization of the genome. This instability has been observed as a delayed expression of lethal mutations, as an enhanced rate of accumulation of non-lethal heritable alterations, and as a progressive intraclonal chromosomal heterogeneity. The genetic controls and biochemical mechanisms underlying radiation-induced genomic instability have not yet been delineated. The aim is to integrate the accumulated evidence that suggests that radiation exposure has a persistent effect on the stability of the mammalian genome.

Protective effect of rare earth against oxidative stress under ultraviolet-B radiation.

PubMed

Wang, Lihong; Huang, Xiaohua; Zhou, Qing

2009-04-01

The effects of lanthanum (III) (La(III)) in protecting soybean leaves against oxidative stress induced by ultraviolet-B (UV-B) radiation were investigated. The increase in contents of hydrogen peroxide (H(2)O(2)) and superoxide (O2*-) due to UV-B radiation suggested oxidative stress. The increase in the content of malondialdehyde (MDA) and the decrease in the index of unsaturated fatty acid (IUFA) indicated oxidative damage on cell membrane induced by UV-B radiation. La(III) partially reversed UV-B-radiation-induced damage of plant growth. The reduction in the contents of H(2)O(2), O2*-, and MDA and increase in the content of IUFA, compared with UV-B treatment, also indicated that La(III) alleviated the oxidative damage induced by UV-B radiation. The increase in the activities of superoxide dismutase and peroxidase and the contents of ascorbate, carotenoids, and flavonoids were observed in soybean leaves with La(III) + UV-B treatment, compared with UV-B treatment. Our data suggested that La(III) could protect soybean plants from UV-B-radiation-induced oxidative stress by reacting with reactive oxygen species directly or by improving the defense system of plants.

Inhibition of the Induced Formation of Tryptophanase in Escherichia coli by Near-Ultraviolet Radiation

PubMed Central

Swenson, P. A.; Setlow, R. B.

1970-01-01

Induced formation of tryptophanase in Escherichia coli B/r is temporarily inhibited by near-ultraviolet (UV) irradiation. The inhibition is greater when irradiation is at 5 C than when at room temperature. Hence, the inhibition is the result of a photochemical, rather than photoenzymatic, alteration of some cellular component. The action spectrum has a peak in the region of 334 nm and is similar to that for growth delay. However, inhibition of tryptophanase formation is more sensitive to near-UV irradiation than are growth, respiration, and the induced formation of β-galactosidase. Thus, for tryptophanase the lack of formation cannot be due to general inhibition of metabolism. Pyridoxal phosphate absorbs in the near-UV region of the spectrum and is a cofactor for tryptophanase, but this enzyme in induced cells is not inactivated by near UV-radiations. An experiment in which toluene-treated suspensions from irradiated and unirradiated cells were mixed showed that irradiation does not cause the formation of an inhibitor of tryptophanase activity. The possibility remains that the absorption of radiant energy by pyridoxal phosphate interferes with the synthesis of tryptophanase. PMID:4914082

Radiation damage effects in far-ultraviolet filters, thin films, and substrates.

PubMed

Keffer, C E; Torr, M R; Zukic, M; Spann, J F; Torr, D G; Kim, J

1994-09-01

Advances in vacuum ultraviolet thin-film filter technology have been made through the use of filter designs with multilayers of materials such as Al(2)O(3), BaF(2), CaF(2), HfO(2), LaF(3), MgF(2), and SiO(2). Our immediate application for these filters will be in an imaging system to be flown on a satellite where a 2 × 9 R(E) orbit will expose the instrument to approximately 250 krad of radiation. Because to our knowledge no previous studies have been made on the potential radiation damage of these materials in the thin-film format, we report on such an assessment here. Transmittances and reflectances of BaF(2), CaF(2), HfO(2), MgF(2), and SiO(2) thin films on MgF(2) substrates, Al(2)O(3) thin films on fused-silica substrates, uncoated fused silica and MgF(2), and four multilayer filters made from these materials were measured from 120 to 180 nm beforeand after irradiation by 250 krad from a (60)Co gamma radiation source. No radiation-induced losses in transmittance or reflectance occurred in this wavelength range. Additional postradiation measurements from 160 to 300 nm indicates 2-5% radiation-induced absorption near 260 nm in some of the samples with MgF(2) substrates. From these measurements we conclude that far-ultraviolet filters made from the materials tested should experience less than 5% change from exposure to up to 250 krad of high-energy radiation in space applications.

Relativistic frequency upshift to the extreme ultraviolet regime using self-induced oscillatory flying mirrors

PubMed Central

Kim, I Jong; Pae, Ki Hong; Kim, Chul Min; Kim, Hyung Taek; Yun, Hyeok; Yun, Sang Jae; Sung, Jae Hee; Lee, Seong Ku; Yoon, Jin Woo; Yu, Tae Jun; Jeong, Tae Moon; Nam, Chang Hee; Lee, Jongmin

2012-01-01

Coherent short-wavelength radiation from laser–plasma interactions is of increasing interest in disciplines including ultrafast biomolecular imaging and attosecond physics. Using solid targets instead of atomic gases could enable the generation of coherent extreme ultraviolet radiation with higher energy and more energetic photons. Here we present the generation of extreme ultraviolet radiation through coherent high-harmonic generation from self-induced oscillatory flying mirrors—a new-generation mechanism established in a long underdense plasma on a solid target. Using a 30-fs, 100-TW Ti:sapphire laser, we obtain wavelengths as short as 4.9 nm for an optimized level of amplified spontaneous emission. Particle-in-cell simulations show that oscillatory flying electron nanosheets form in a long underdense plasma, and suggest that the high-harmonic generation is caused by reflection of the laser pulse from electron nanosheets. We expect this extreme ultraviolet radiation to be valuable in realizing a compact X-ray instrument for research in biomolecular imaging and attosecond physics. PMID:23187631

[Ultraviolet radiation and long term space flight].

PubMed

Wu, H B; Su, S N; Ba, F S

2000-08-01

With the prolongation of space flight, influences of various aerospace environmental factors on the astronauts become more and more severe, while ultraviolet radiation is lacking. Some studies indicated that low doses of ultraviolet rays are useful and essential for human body. In space flight, ultraviolet rays can improve the hygienic condition in the space cabin, enhance astronaut's working ability and resistance to unfavorable factors, prevent mineral metabolic disorders, cure purulent skin diseases and deallergize the allergens. So in long-term space flight, moderate amount of ultraviolet rays in the space cabin would be beneficial.

Binding of radiation-induced phenylalanine radicals to DNA: influence on the biological activity of the DNA and on its sensitivity to the induction of breaks by gamma rays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vanderschans, G.P.; Vanrijn, C.J.S.; Bleichrodt, J.F.

1975-11-01

When an aqueous solution of double-stranded deoxyribonucleic acid (DNA) of bacteriophage PM2 containing phenylalanine and saturated with N2O is irradiated with gamma rays, radiation induced phenylalanine radicals are bound covalently. Under the conditions used about 25 phenylalanine molecules may be bound per lethal hit. Also for single-stranded PM2 DNA most of the phenylalanine radicals bound are nonlethal. Evidence is presented that in double-stranded DNA an appreciable fraction of the single-strand breaks is induced by phenylalanine radicals. Radiation products of phenylalanine and the phenylalanine bound to the DNA decrease the sensitivity of the DNA to the induction of single-strand breaks. Theremore » are indications that the high efficiency of protection by radiation products of phenylalanine is due to their positive charge, which will result in a relatively high concentration of these compounds in the vicinity of the negatively charged DNA molecules. (Author) (GRA)« less

Ocean Acidification Alters the Photosynthetic Responses of a Coccolithophorid to Fluctuating Ultraviolet and Visible Radiation1[OPEN

PubMed Central

Jin, Peng; Gao, Kunshan; Villafañe, Virginia E.; Campbell, Douglas A.; Helbling, E. Walter

2013-01-01

Mixing of seawater subjects phytoplankton to fluctuations in photosynthetically active radiation (400–700 nm) and ultraviolet radiation (UVR; 280–400 nm). These irradiance fluctuations are now superimposed upon ocean acidification and thinning of the upper mixing layer through stratification, which alters mixing regimes. Therefore, we examined the photosynthetic carbon fixation and photochemical performance of a coccolithophore, Gephyrocapsa oceanica, grown under high, future (1,000 μatm) and low, current (390 μatm) CO2 levels, under regimes of fluctuating irradiances with or without UVR. Under both CO2 levels, fluctuating irradiances, as compared with constant irradiance, led to lower nonphotochemical quenching and less UVR-induced inhibition of carbon fixation and photosystem II electron transport. The cells grown under high CO2 showed a lower photosynthetic carbon fixation rate but lower nonphotochemical quenching and less ultraviolet B (280–315 nm)-induced inhibition. Ultraviolet A (315–400 nm) led to less enhancement of the photosynthetic carbon fixation in the high-CO2-grown cells under fluctuating irradiance. Our data suggest that ocean acidification and fast mixing or fluctuation of solar radiation will act synergistically to lower carbon fixation by G. oceanica, although ocean acidification may decrease ultraviolet B-related photochemical inhibition. PMID:23749851

Clustered DNA damages induced in human hematopoietic cells by low doses of ionizing radiation

NASA Technical Reports Server (NTRS)

Sutherland, Betsy M.; Bennett, Paula V.; Cintron-Torres, Nela; Hada, Megumi; Trunk, John; Monteleone, Denise; Sutherland, John C.; Laval, Jacques; Stanislaus, Marisha; Gewirtz, Alan

2002-01-01

Ionizing radiation induces clusters of DNA damages--oxidized bases, abasic sites and strand breaks--on opposing strands within a few helical turns. Such damages have been postulated to be difficult to repair, as are double strand breaks (one type of cluster). We have shown that low doses of low and high linear energy transfer (LET) radiation induce such damage clusters in human cells. In human cells, DSB are about 30% of the total of complex damages, and the levels of DSBs and oxidized pyrimidine clusters are similar. The dose responses for cluster induction in cells can be described by a linear relationship, implying that even low doses of ionizing radiation can produce clustered damages. Studies are in progress to determine whether clusters can be produced by mechanisms other than ionizing radiation, as well as the levels of various cluster types formed by low and high LET radiation.

A FLUORESCENCE BASED ASSAY FOR DNA DAMAGE INDUCED BY RADIATION, CHEMICAL MUTAGENS AND ENZYMES

EPA Science Inventory

A simple and rapid assay to detect DNA damage is reported. This novel assay is based on changes in melting/annealing behavior and facilitated using certain dyes that increase their fluorescence upon association with double stranded (ds)DNA. Damage caused by ultraviolet (UV) ra...

A direct view by immunofluorescent comet assay (IFCA) of DNA damage induced by nicking and cutting enzymes, ionizing (137)Cs radiation, UV-A laser microbeam irradiation and the radiomimetic drug bleomycin.

PubMed

Grigaravicius, Paulius; Rapp, Alexander; Greulich, Karl Otto

2009-03-01

In DNA repair research, DNA damage is induced by different agents, depending on the technical facilities of the investigating researchers. A quantitative comparison of different investigations is therefore often difficult. By using a modified variant of the neutral comet assay, where the histone H1 is detected by immunofluorescence [immunofluorescent comet assay (IFCA)], we achieve previously unprecedented resolution in the detection of fragmented chromatin and show that trillions of ultraviolet A photons (of a few eV), billions of bleomycin (BLM) molecules and thousands of gamma quanta (of 662 keV) generate, in first order, similar damage in the chromatin of HeLa cells. A somewhat more detailed inspection shows that the damage caused by 20 Gy ionizing radiation and by a single laser pulse of 10 microJ are comparable, while the damage caused by 12 microg/ml BLM depends highly on the individual cell. Taken together, this work provides a detailed view of DNA fragmentation induced by different treatments and allows comparing them to some extent, especially with respect to the neutral comet assay.

ULTRAVIOLET PROTECTIVE COMPOUNDS AS A RESPONSE TO ULTRAVIOLET RADIATION EXPOSURE

EPA Science Inventory

Life on Earth has evolved adaptations to many environmental stresses over the epochs. One consistent stress has been exposure to ultraviolet radiation. In response to UVR organisms have adapted myriad responses; behavioral, morphological and physiological. Behaviorally, some orga...

Low concentration of arsenite exacerbates UVR-induced DNA strand breaks by inhibiting PARP-1 activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin Xujun; Department of Toxicology, Fourth Military Medical University, Xi'an, Shaanxi, 710032; Hudson, Laurie G.

2008-10-01

Epidemiological studies have associated arsenic exposure with many types of human cancers. Arsenic has also been shown to act as a co-carcinogen even at low concentrations. However, the precise mechanism of its co-carcinogenic action is unknown. Recent studies indicate that arsenic can interfere with DNA-repair processes. Poly(ADP-ribose) polymerase (PARP)-1 is a zinc-finger DNA-repair protein, which can promptly sense DNA strand breaks and initiate DNA-repair pathways. In the present study, we tested the hypothesis that low concentrations of arsenic could inhibit PAPR-1 activity and so exacerbate levels of ultraviolet radiation (UVR)-induced DNA strand breaks. HaCat cells were treated with arsenite and/ormore » UVR, and then DNA strand breaks were assessed by comet assay. Low concentrations of arsenite ({<=} 2 {mu}M) alone did not induce significant DNA strand breaks, but greatly enhanced the DNA strand breaks induced by UVR. Further studies showed that 2 {mu}M arsenite effectively inhibited PARP-1 activity. Zinc supplementation of arsenite-treated cells restored PARP-1 activity and significantly diminished the exacerbating effect of arsenite on UVR-induced DNA strand breaks. Importantly, neither arsenite treatment, nor zinc supplementation changed UVR-triggered reactive oxygen species (ROS) formation, suggesting that their effects upon UVR-induced DNA strand breaks are not through a direct free radical mechanism. Combination treatments of arsenite with PARP-1 inhibitor 3-aminobenzamide or PARP-1 siRNA demonstrate that PARP-1 is the target of arsenite. Together, these findings show that arsenite at low concentration exacerbates UVR-induced DNA strand breaks by inhibiting PARP-1 activity, which may represent an important mechanism underlying the co-carcinogenicity of arsenic.« less

Abnormal ultraviolet mutagenic spectrum in plasmid DNA replicated in cultured fibroblasts from a patient with the skin cancer-prone disease, xeroderma pigmentosum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seetharam, S.; Protic-Sabljic, M.; Seidman, M.M.

1987-12-01

A shuttle vector plasmid, pZ189, was utilized to assess the types of mutations that cells from a patient with xeroderma pigmentosum, complementation group D, introduce into ultraviolet (UV) damaged, replicating DNA. Patients with xeroderma pigmentosum have clinical and cellular UV hypersensitivity, increased frequency of sun-induced skin cancer, and deficient DNA repair. In comparison to UV-treated pZ189 replicated in DNA repair-proficient cells, there were fewer surviving plasmids, a higher frequency of plasmids with mutations, fewer plasmids with two or more mutations in the marker gene, and a new mutagenic hotspot. The major type of base substitution mutation was the G:C tomore » A:T transition with both cell lines. These results, together with similar findings published earlier with cells from a xeroderma pigmentosum patient in complementation group A, suggest that isolated G:C to A:T somatic mutations may be particularly important in generation of human skin cancer by UV radiation.« less

Modelling and Holographic Visualization of Space Radiation-Induced DNA Damage

NASA Technical Reports Server (NTRS)

Plante, Ianik

2017-01-01

Space radiation is composed by a mixture of ions of different energies. Among these, heavy inos are of particular importance because their health effects are poorly understood. In. the recent years, a software named RITRACKS (Relativistic Ion Tracks) was developed to simulate the detailed radiation track structure, several DNA models and DNA damage. As the DNA structure is complex due to packing, it is difficult to the damage using a regular computer screen.

Fluorescence of molecular hydrogen excited by solar extreme-ultraviolet radiation

NASA Technical Reports Server (NTRS)

Feldman, P. D.; Fastie, W. G.

1973-01-01

During trans-earth coast, the Apollo 17 ultraviolet spectrometer was scheduled to make observations of the far ultraviolet background in selected regions of the sky. In the course of one of these observations, the spacecraft fuel cells were routinely purged of excess hydrogen and water vapor. The ultraviolet fluorescence spectrum of the purged molecular hydrogen excited by solar extreme ultraviolet radiation is interpreted by absorption of solar L-beta and L-gamma radiation in the nearly resonant (6, 0) and (11, 0) Lyman bands. The results are deemed significant for ultraviolet spectroscopic investigations of the atmospheres of the moon and planets since Lyman-band fluorescence provides an unambiguous means of identification of molecular hydrogen in upper atmospheres.

STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type I Interferon-Dependent Antitumor Immunity in Immunogenic Tumors.

PubMed

Deng, Liufu; Liang, Hua; Xu, Meng; Yang, Xuanming; Burnette, Byron; Arina, Ainhoa; Li, Xiao-Dong; Mauceri, Helena; Beckett, Michael; Darga, Thomas; Huang, Xiaona; Gajewski, Thomas F; Chen, Zhijian J; Fu, Yang-Xin; Weichselbaum, Ralph R

2014-11-20

Ionizing radiation-mediated tumor regression depends on type I interferon (IFN) and the adaptive immune response, but several pathways control I IFN induction. Here, we demonstrate that adaptor protein STING, but not MyD88, is required for type I IFN-dependent antitumor effects of radiation. In dendritic cells (DCs), STING was required for IFN-? induction in response to irradiated-tumor cells. The cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) mediated sensing of irradiated-tumor cells in DCs. Moreover, STING was essential for radiation-induced adaptive immune responses, which relied on type I IFN signaling on DCs. Exogenous IFN-? treatment rescued the cross-priming by cGAS or STING-deficient DCs. Accordingly, activation of STING by a second messenger cGAMP administration enhanced antitumor immunity induced by radiation. Thus radiation-mediated antitumor immunity in immunogenic tumors requires a functional cytosolic DNA-sensing pathway and suggests that cGAMP treatment might provide a new strategy to improve radiotherapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Coral Skeletons Defend against Ultraviolet Radiation

PubMed Central

Reef, Ruth; Kaniewska, Paulina; Hoegh-Guldberg, Ove

2009-01-01

Background Many coral reef organisms are photosynthetic or have evolved in tight symbiosis with photosynthetic symbionts. As such, the tissues of reef organisms are often exposed to intense solar radiation in clear tropical waters and have adapted to trap and harness photosynthetically active radiation (PAR). High levels of ultraviolet radiation (UVR) associated with sunlight, however, represent a potential problem in terms of tissue damage. Methodology/Principal Findings By measuring UVR and PAR reflectance from intact and ground bare coral skeletons we show that the property of calcium carbonate skeletons to absorb downwelling UVR to a significant extent, while reflecting PAR back to the overlying tissue, has biological advantages. We placed cnidarians on top of bare skeletons and a UVR reflective substrate and showed that under ambient UVR levels, UVR transmitted through the tissues of cnidarians placed on top of bare skeletons were four times lower compared to their counterparts placed on a UVR reflective white substrate. In accordance with the lower levels of UVR measured in cnidarians on top of coral skeletons, a similar drop in UVR damage to their DNA was detected. The skeletons emitted absorbed UVR as yellow fluorescence, which allows for safe dissipation of the otherwise harmful radiation. Conclusions/Significance Our study presents a novel defensive role for coral skeletons and reveals that the strong UVR absorbance by the skeleton can contribute to the ability of corals, and potentially other calcifiers, to thrive under UVR levels that are detrimental to most marine life. PMID:19946361

Two ultraviolet radiation datasets that cover China

NASA Astrophysics Data System (ADS)

Liu, Hui; Hu, Bo; Wang, Yuesi; Liu, Guangren; Tang, Liqin; Ji, Dongsheng; Bai, Yongfei; Bao, Weikai; Chen, Xin; Chen, Yunming; Ding, Weixin; Han, Xiaozeng; He, Fei; Huang, Hui; Huang, Zhenying; Li, Xinrong; Li, Yan; Liu, Wenzhao; Lin, Luxiang; Ouyang, Zhu; Qin, Boqiang; Shen, Weijun; Shen, Yanjun; Su, Hongxin; Song, Changchun; Sun, Bo; Sun, Song; Wang, Anzhi; Wang, Genxu; Wang, Huimin; Wang, Silong; Wang, Youshao; Wei, Wenxue; Xie, Ping; Xie, Zongqiang; Yan, Xiaoyuan; Zeng, Fanjiang; Zhang, Fawei; Zhang, Yangjian; Zhang, Yiping; Zhao, Chengyi; Zhao, Wenzhi; Zhao, Xueyong; Zhou, Guoyi; Zhu, Bo

2017-07-01

Ultraviolet (UV) radiation has significant effects on ecosystems, environments, and human health, as well as atmospheric processes and climate change. Two ultraviolet radiation datasets are described in this paper. One contains hourly observations of UV radiation measured at 40 Chinese Ecosystem Research Network stations from 2005 to 2015. CUV3 broadband radiometers were used to observe the UV radiation, with an accuracy of 5%, which meets the World Meteorology Organization's measurement standards. The extremum method was used to control the quality of the measured datasets. The other dataset contains daily cumulative UV radiation estimates that were calculated using an all-sky estimation model combined with a hybrid model. The reconstructed daily UV radiation data span from 1961 to 2014. The mean absolute bias error and root-mean-square error are smaller than 30% at most stations, and most of the mean bias error values are negative, which indicates underestimation of the UV radiation intensity. These datasets can improve our basic knowledge of the spatial and temporal variations in UV radiation. Additionally, these datasets can be used in studies of potential ozone formation and atmospheric oxidation, as well as simulations of ecological processes.

Aqueous humour and ultraviolet radiation.

PubMed

Ringvold, A

1980-01-01

Studies on the ultraviolet ray absorption in the aqueous humour of rabbit, cat, monkey, guinea pig, and rat showed marked species differences. In the rabbit aqueous the ascorbic acid, the proteins, and some amino acids (tyrosine, phenylalanine, cystine, and tryptophane) are together responsible for the total absorption, and a very great part of it refers to the ascorbic acid content. Accordingly, species with significant amounts of ascorbic acid in the aqueous (monkey, rabbit, guinea pig) have a greater absorption capacity towards ultraviolet radiation than species (cat, rat) lacking this substance. This effect of the ascorbic acid may contribute in protecting the lens against the most biotoxic ultraviolet rays. It seems that the ascorbic acid concentration is highest in the aqueous of typical day animals and lowest in species being active in the dark, indicating a correlation between the aqueous' ascorbic acid level and the quantity of incident light on the eye. The possible significance of changed aqueous ultraviolet ray absorption in the pathogenesis of human cataract development is discussed.

Ultraviolet-B radiation induces modulation of antigen presentation of herpes simplex virus by human epidermal cells.

PubMed

van der Molen, R G; Out-Luiting, C; Claas, F H; Norval, M; Koerten, H K; Mommaas, A M

2001-06-01

Although ultraviolet (UV) B radiation is known to be immunosuppressive, there is little information regarding a relevant immunological endpoint to assess human subjects in vivo. Therefore, we have examined the effect of in vivo UV radiation on the ability of human epidermal cells (EC) to present herpes simplex virus (HSV) antigens to memory T cells. Human volunteers, who were seropositive for HSV, were exposed to one minimal erythemal dose (MED) for four consecutive days. EC, prepared from suction blister roofs, were co-cultured with autologous T cells in the presence of HSV. HSV antigen presentation by UV-exposed EC was increased compared with control, nonexposed EC. This up-regulation correlated with an influx of macrophages into the epidermis, which are considered to be associated with UV-induced tolerance. Altering the UV protocol to a sub-erythemal UV dose for four consecutive days or to a single high dose of 2 MED, resulted in suppressed HSV antigen presentation, without the influx of the UV-macrophages. One of the goals of the present study was to eventually use this HSV system to investigate sunscreen immunoprotection. A pilot study with a TiO2-containing sunscreen suggested that the endpoint for UV-induced immunosuppression presented here is promising to be used for human in vivo sunscreen immunoprotection studies.

[Effect of long-wave ultraviolet light (UV-A) and medium-wave ultraviolet rays (UV-B) on human skin. Critical comparison].

PubMed

Raab, W

1980-04-15

When discussing the effects of ultraviolet radiation on human skin, one should carefully distinguish between the long wave ultraviolet light (UV-A) and the short wave radiations (UV-B and UV-C). Ultraviolet A induces immediate pigmentation but, if high energies are applied, a permanent pigmentation is elicited. This type of ultraviolet A-induced pigmentation has been called "spontaneous" pigmentation as no erythematous reaction is necessary to induce or accelerate melanine formation. Ultraviolet B provokes erythema and consecutive pigmentation. Upon chronic exposure, ultraviolet B causes the wellknown actinic damage of the skin and even provokes carcinoma. With exposures to the sunlight (global radiation), one should be most careful. The public must be informed extensively about the dangers of excessive sunbaths. The use of artificial "suns" with spectra between 260 and 400 nm is limited as it may cause the same type of damage as the global radiation. An exact schedule for use of artificial lamps is strongly recommended. After one cycle of exposures, an interruption is necessary until the next cycle of irradiations may start. Upon continual use for tanning of the skin, artificial lamps may provoke irreversible damage of the skin. Radiation sources with emission spectra of wavelengths between 315 and 400 nm exclusively are well suited for the induction of skin pigmentation (cosmetic use). Potent radiation such as UVASUN systems provoke a "pleasant" permanent pigmentation after exposures for less than one hour. The use of ultraviolet A (UV-A) does not carry any risk for the human skin.

Evaluation of γ-radiation-induced DNA damage in two species of bivalves and their relative sensitivity using comet assay.

PubMed

Praveen Kumar, M K; Shyama, S K; Sonaye, B S; Naik, U Roshini; Kadam, S B; Bipin, P D; D'costa, A; Chaubey, R C

2014-05-01

Ionizing radiation is known to induce genetic damage in diverse groups of organisms. Under accidental situations, large quantities of radioactive elements get released into the environment and radiation emitted from these radionuclides may adversely affect both the man and the non-human biota. The present study is aimed (a) to know the genotoxic effect of gamma radiation on aquatic fauna employing two species of selected bivalves, (b) to evaluate the possible use of 'Comet assay' for detecting genetic damage in haemocytes of bivalves as a biomarker for environmental biomonitoring and also (c) to compare the relative sensitivity of two species of bivalves viz. Paphia malabarica and Meretrix casta to gamma radiation. The comet assays was optimized and validated using different concentrations (18, 32 and 56 mg/L) of ethyl methanesulfonate (EMS), a direct-acting reference genotoxic agent, to which the bivalves were exposed for various times (24, 48 and 72 h). Bivalves were irradiated (single acute exposure) with 5 different doses (viz. 2, 4, 6, 8 and 10 Gy) of gamma radiation and their genotoxic effects on the haemocytes were studied using the comet assay. Haemolymph was collected from the adductor muscle at 24, 48 and 72 h of both EMS-exposed and irradiated bivalves and comet assay was carried out using standard protocol. A significant increase in DNA damage was observed as indicated by an increase in % tail DNA damage at different concentrations of EMS and all the doses of gamma radiation as compared to controls in both bivalve species. This showed a dose-dependent increase of genetic damage induced in bivalves by EMS as well as gamma radiation. Further, the highest DNA damage was observed at 24h. The damage gradually decreased with time, i.e. was smaller at 48 and 72 h than at 24h post irradiation in both species of bivalves. This may indicate repair of the damaged DNA and/or loss of heavily damaged cells as the post irradiation time advanced. The present study

Radiation-induced damage to cellular DNA: Chemical nature and mechanisms of lesion formation

NASA Astrophysics Data System (ADS)

Cadet, Jean; Wagner, J. Richard

2016-11-01

This mini-review focuses on the recent identification of several novel radiation-induced single and tandem modifications in cellular DNA. For this purpose accurate high-performance electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was applied allowing their quantitative measurement and unambiguous characterization. Exposure of human cells to gamma rays led to the formation of several modified bases arising from the rearrangement of the pyrimidine ring of thymine, cytosine and 5-methylcytosine subsequent to initial addition of an hydroxyl radical (•OH) to the 5,6-ethylenic bond. In addition, 5-hydroxymethylcytosine, an novel epigenetic mark, and 5-formylcytosine, were found to be generated consecutively to •OH-mediated hydrogen abstraction from the methyl group of 5-methylcytosine. Relevant mechanistic information on one-oxidation reactions of cellular DNA was also gained from the detection of 5-hydroxycytosine and guanine-thymine intra-strand adducts whose formation is rationalized by the generation of related base radical cation. Attempts to search for the radiation-induced formation of purine 5‧,8-cyclo-2‧-deoxyribonucleosides were unsuccessful with the exception of trace amounts of (5‧S)-5‧,8-cyclo-2‧-deoxyadenosine.

Probabilities of radiation-induced inter- and intrachromosomal exchanges and their dependence on the DNA content of the chromosome

NASA Technical Reports Server (NTRS)

Wu, H.; Yang, T. C. (Principal Investigator)

2001-01-01

A biophysical model has been developed that is based on the assumptions that an interphase chromosome occupies a spherical territory and that chromosome exchanges are formed by the misrejoining of two DNA double-strand breaks induced within a defined interaction distance. The model is used to explain the relative frequencies of inter- and intrachromosomal exchanges and the relationship between radiation-induced aberrations in individual chromosomes and the DNA content of the chromosome. Although this simple model predicts a higher ratio of inter- to intrachromosomal exchanges for low-LET radiation than for high-LET radiation, as has been suggested by others, we argue that the comparison of the prediction of the model with experimental results is not straightforward. With the model, we also show that the probability of the formation of interchromosomal exchanges is proportional to the "surface area" of the chromosome domain plus a correction term. The correction term is small if the interaction distance is less than 1 microm for both low- and high-LET radiations.

DNA damage by various radiations

NASA Astrophysics Data System (ADS)

Hasegawa, K.; Yoshioka, H.; Yoshioka, H.

1997-01-01

In an attempt to shed light on the influence of tritiated water on DNA we have investigated the post-irradiation damage with a simple plasmid DNA, pBR322 and pUC18. The survival of covalently closed circular (CCC) DNA form was directly followed by agarose gel electrophoresis. The survival percentage of DNA in tritiated water was almost the same as with the irradiation with X-rays at the same absorbed dose. For irradiation with γ-rays, on the other hand, the decay rate was larger than those observed with both tritiated water and X-rays. The percentages of breakage for DNA in tritiated water, X-rays and γ-rays were found to be 34, 38 and 33% at 100 Gy of absorbed dose. The effect of dose rate was not observed for irradiation with tritiated water, X-rays and γ-rays. In order to study protection of DNA against radiation, we investigated the protecting effect of tea catechin which is the main component of (-)-epigallocatechin gallate (EGCg). The protection mechanism for DNA against radiation-induced scission has been studied using ESR spin-trapping method.

Heme oxygenase up-regulation under ultraviolet-B radiation is not epigenetically restricted and involves specific stress-related transcriptions factors.

PubMed

Santa-Cruz, Diego; Pacienza, Natalia; Zilli, Carla; Pagano, Eduardo; Balestrasse, Karina; Yannarelli, Gustavo

2017-08-01

Heme oxygenase-1 (HO-1) plays a protective role against oxidative stress in plants. The mechanisms regulating its expression, however, remain unclear. Here we studied the methylation state of a GC rich HO-1 promoter region and the expression of several stress-related transcription factors (TFs) in soybean plants subjected to ultraviolet-B (UV-B) radiation. Genomic DNA and total RNA were isolated from leaves of plants irradiated with 7.5 and 15kJm-2 UV-B. A 304bp HO-1 promoter region was amplified by PCR from sodium bisulfite-treated DNA, cloned into pGEMT plasmid vector and evaluated by DNA sequencing. Bisulfite sequencing analysis showed similar HO-1 promoter methylation levels in control and UV-B-treated plants (C: 3.4±1.3%; 7.5: 2.6±0.5%; 15: 3.1±1.1%). Interestingly, HO-1 promoter was strongly unmethylated in control plants. Quantitative RT-PCR analysis of TFs showed that GmMYB177, GmMYBJ6, GmWRKY21, GmNAC11, GmNAC20 and GmGT2A but not GmWRK13 and GmDREB were induced by UV-B radiation. The expression of several TFs was also enhanced by hemin, a potent and specific HO inducer, inferring that they may mediate HO-1 up-regulation. These results suggest that soybean HO-1 gene expression is not epigenetically regulated. Moreover, the low level of HO-1 promoter methylation suggests that this antioxidant enzyme can rapidly respond to environmental stress. Finally, this study has identified some stress-related TFs involved in HO-1 up-regulation under UV-B radiation. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Ultraviolet radiation-induced cataract in mice: the effect of age and the potential biochemical mechanism.

PubMed

Zhang, Jie; Yan, Hong; Löfgren, Stefan; Tian, Xiaoli; Lou, Marjorie F

2012-10-19

To study the effect of age on the morphologic and biochemical alterations induced by in vivo exposure of ultraviolet radiation (UV). Young and old C57BL/6 mice were exposed to broadband UVB+UVA and euthanized after 2 days. Another batch of UV-exposed young mice was monitored for changes after 1, 2, 4, and 8 days. Age-matched nonexposed mice served as controls. Lens changes were documented in vivo by slit-lamp biomicroscopy and dark field microscopy photographs ex vivo. Lens homogenates were analyzed for glutathione (GSH) level, and the activities of thioredoxin (Trx), thioltransferase (TTase), and glyceraldehyde-3-phosphate dehydrogenase (G3PD). Glutathionylated lens proteins (PSSGs) were detected by immunoblotting using GSH antibody. Western blot analysis was also done for the expression levels of TTase and Trx. Both age groups developed epithelial and superficial anterior subcapsular cataract at 2 days postexposure. The lens GSH level and G3PD activity were decreased, and PSSGs were elevated in both age groups, but more prominent in the older mice. TTase and Trx activity and protein expression were elevated only in the young mice. Interestingly, lens TTase and Trx in the young mice showed a transient increase, peaking at 2 days after UV exposure and returning to baseline at day 8, corroborated by lens transparency. The lenses of old mice were more susceptible to UV radiation-induced cataract. The upregulated TTase and Trx likely provided oxidation damage repair in the young mice.

Photoluminescence emission spectra of Makrofol® DE 1-1 upon irradiation with ultraviolet radiation

NASA Astrophysics Data System (ADS)

El Ghazaly, M.; Aydarous, Abdulkadir

Photoluminescence (PL) emission spectra of Makrofol® DE 1-1 (bisphenol-A based polycarbonate) upon irradiation with ultraviolet radiation of different wavelengths were investigated. The absorption-and attenuation coefficient measurements revealed that the Makrofol® DE 1-1 is characterized by high absorbance in the energy range 6.53-4.43 eV but for a lower energy than 4.43 eV, it is approximately transparent. Makrofol® DE 1-1 samples were irradiated with ultraviolet radiation of wavelength in the range from 250 (4.28 eV) to 400 (3.10 eV) nm in step of 10 nm and the corresponding photoluminescence (PL) emission spectra were measured with a spectrofluorometer. It is found that the integrated counts and the peak height of the photoluminescence emission (PL) bands are strongly correlated with the ultraviolet radiation wavelength. They are increased at the ultraviolet radiation wavelength 280 nm and have maximum at 290 nm, thereafter they decrease and diminish at 360 nm of ultraviolet wavelength. The position of the PL emission band peak was red shifted starting from 300 nm, which increased with the increase the ultraviolet radiation wavelength. The PL bandwidth increases linearly with the increase of the ultraviolet radiation wavelength. When Makrofol® DE 1-1 is irradiated with ultraviolet radiation of short wavelength (UVC), the photoluminescence emission spectra peaks also occur in the UVC but of a relatively longer wavelength. The current new findings should be considered carefully when using Makrofol® DE 1-1 in medical applications related to ultraviolet radiation.

Elastomeric Seal Performance after Terrestrial Ultraviolet Radiation Exposure

NASA Technical Reports Server (NTRS)

Daniels, Christopher C.; Oravec, Heather A.; Mather, Janice L.; Taylor, Shawn C.; Dunlap, Patrick H.

2015-01-01

Ultraviolet radiation was evaluated to determine its negative effects on the performance of elastomeric gas pressure seals. The leak rates of the silicone elastomer S0383-70 O-ring test articles were used to quantify the degradation of the seals after exposure to vacuum-ultraviolet and/or middle-to-near-ultraviolet wavelength radiation. Three groups of seals were exposed in terrestrial facilities to 115-165 nm wavelength radiation, 230-500 nm wavelength radiation, or both spectrums, for an orbital spaceflight equivalent of 125 hours. The leak rates of the silicone elastomer S0383-70 seals were quantified and compared to samples that received no radiation. Each lot contained six samples and statistical t-tests were used to determine the separate and combined influences of exposure to the two wavelength ranges. A comparison of the mean leak rates of samples exposed to 115-165 nm wavelength radiation to the control specimens showed no difference, suggesting that spectrum was not damaging. The 230-500 nm wavelength appeared to be damaging, as the mean leak rates of the specimens exposed to that range of wavelengths, and those exposed to the combined 115-165 nm and 230-500 nm spectrums, were significantly different from the leak rates of the control specimens. Most importantly, the test articles exposed to both wavelength spectrums exhibited mean leak rates two orders of magnitude larger than any other exposed specimens, which suggested that both wavelength spectrums are important when simulating the orbital environment.

Solar ultraviolet radiation and its impact on aquatic systems of Patagonia, South America.

PubMed

Villafañe, V E; Helbling, E W; Zagarese, H E

2001-03-01

Solar ultraviolet radiation (UVR, 280-400 nm) is known to cause a number of detrimental effects in aquatic organisms. The area of Patagonia, which is sometimes under the influence of the Antarctic ozone "hole", occasionally receives enhanced levels of ultraviolet B radiation (UV-B, 280-315 nm). Great efforts have been put into creating a database for UVR climatology by installing a variety of instruments in several localities in the region. However, no comparable effort has been made to determine the impact of normal and enhanced levels of solar UVR upon organisms. Most of the photobiological research in aquatic systems of Patagonia has focused on determining the effects of solar UVR in phytoplankton photosynthesis, DNA damage, and mortality, fecundity and repair mechanisms in zooplanktonic species. Some work has also been done with fish larvae and interactions between species at low trophic levels of the aquatic food web. The results of these studies indicate that in order to assess the overall impact of UVR in a certain waterbody, it is also necessary to consider other variables, such as changes in cloudiness, ozone concentrations, differential sensitivity of organisms, and depth of the upper mixed layer/epilimnion. All factors that can preclude or benefit the acclimation of species to solar radiation.

Characterization of photoluminescence spectra from poly allyl diglycol carbonate (CR-39) upon excitation with the ultraviolet radiation of various wavelengths

NASA Astrophysics Data System (ADS)

El Ghazaly, M.; Al-Thomali, Talal A.

2013-04-01

The induced photoluminescence (PL) from the π-conjugated polymer poly allyl diglycol carbonate (PADC) (CR-39) upon excitation with the ultraviolet radiation of different wavelengths was investigated. The absorption and attenuation coefficients of PADC (CR-39) were recorded using a UV-visible spectrometer. It was found that the absorption and attenuation coefficients of the PADC (CR-39) exhibit a strong dependence on the wavelength of ultraviolet radiation. The PL spectra were measured with a Flormax-4 spectrofluorometer (Horiba). PADC (CR-39) samples were excited by ultraviolet radiation with wavelengths in the range from 260 to 420 nm and the corresponding PL emission bands were recorded. The obtained results show a strong correlation between the PL and the excitation wavelength of ultraviolet radiation. The position of the fluorescence emission band peak was red shifted starting from 300 nm, which was increased with the increase in the excitation wavelength. The PL yield and its band peak height were increased with the increase in the excitation wavelength till 290 nm, thereafter they decreased exponentially with the increase in the ultraviolet radiation wavelength. These new findings should be considered carefully during the use of the PADC (CR-39) in the scientific applications and in using PADC (CR-39) in eyeglasses.

Photosynthetic carbon reduction by seagrasses exposed to ultraviolet A radiation

NASA Technical Reports Server (NTRS)

1979-01-01

The seagrasses Halophila engelmannii, Halodule wrightii, and Syringodium filiforme were examined for their intrinsic sensitivity to ultraviolet-A-UV-A and ultraviolet-B-UV-B radiation. The effect of UV-A on photosynthetically active radiation (PAR) was also determined. Ultraviolet-A and ultraviolet-B were studied with emphasis on the greater respective environmental consequence in terms of seagrass distribution and abundance. Results indicate that an intrinsic sensitivity to UV-A alone is apparent only in Halophila, while net photosynthesis in Halodule and Syringodium seems unaffected by the level of UV-A provided. The sensitivity of Halophila to UV-A in the absense of (PAR) indicates that the photosynthetic reaction does not need to be in operation for damage to occur. Other significant results are reported.

Nitric oxide alleviates oxidative damage induced by enhanced ultraviolet-B radiation in cyanobacterium.

PubMed

Xue, Lingui; Li, Shiweng; Sheng, Hongmei; Feng, Huyuan; Xu, Shijian; An, Lizhe

2007-10-01

To study the role of nitric oxide (NO) on enhanced ultraviolet-B (UV-B) radiation (280-320 nm)-induced damage of Cyanobacterium, the growth, pigment content, and antioxidative activity of Spirulina platensis-794 cells were investigated under enhanced UV-B radiation and under different chemical treatments with or without UV-B radiation for 6 h. The changes in chlorophyll-a, malondialdehyde content, and biomass confirmed that 0.5 mM: sodium nitroprusside (SNP), a donor of nitric oxide (NO), could markedly alleviate the damage caused by enhanced UV-B. Specifically, the biomass and the chlorophyll-a content in S. platensis-794 cells decreased 40% and 42%, respectively under enhanced UV-B stress alone, but they only decreased 10% and 18% in the cells treated with UV-B irradiation and 0.5 mM: SNP. Further experiments suggested that NO treatment significantly increased the activities of superoxide dismutase (SOD) and catalase (CAT), and decreased the accumulation of O (2)(-) in enhanced UV-B-irradiated cells. SOD and CAT activity increased 0.95- and 6.73-fold, respectively. The accumulation of reduced glutathione (GSH) increased during treatment with 0.5 mM: SNP in normal S. platensis cells, but SNP treatment could inhibit the increase of GSH in enhanced UV-B-stressed S. platensis cells. Thus, these results suggest that NO can strongly alleviate oxidative damage caused by UV-B stress by increasing the activities of SOD, peroxidase, CAT, and the accumulation of GSH, and by eliminating O (2)(-) in S. platensis-794 cells. In addition, the difference of NO origin between plants and cyanobacteria are discussed.

Xeroderma pigmentosum neurological abnormalities correlate with colony-forming ability after ultraviolet radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andrews, A.D.; Barrett, S.F.; Robbins, J.H.

1978-04-01

Xeroderma pigmentosum is an autosomal recessive disease in which DNA repair processes are defective. All xeroderma pigmentosum patients develop premature aging of sun exposed skin, and some develop neurological abnormalities due to premature death of nerve cells. Sensitivity to ultraviolet radiation of 24 xeroderma pigmentosum fibroblast strains was studied in vitro by measuring each strain's ability to divide and form colonies after irradiation. The most sensitive strains were derived from patients who had an early onset of neurological abnormalities; less sensitive strains were from patients with a later onset; and the most resistant strains were from patients without neurological abnormalities.more » The uv sensitivities of strains from each member of a sibling pair with xeroderma pigmentosum were identical, indicating that uv sensitivity of xeroderma pigmentosum strains is determined by the patient's inherited DNA repair defect. The results suggest that effective DNA repair is required to maintain the functional integrity of the human nervous system by preventing premature death of neurons.« less

The repair of low dose UV light-induced damage to human skin DNA in condition of trace amount Mg 2+

NASA Astrophysics Data System (ADS)

Gao, Fang; Guo, Zhouyi; Zheng, Changchun; Wang, Rui; Liu, Zhiming; Meng, Pei; Zhai, Juan

2008-12-01

Ultraviolet light-induced damage to human skin DNA was widely investigated. The primary mechanism of this damage contributed to form cyclobutane pyrimidine dimmers (CPDs). Although the distribution of UV light-induced CPDs within a defined sequence is similar, the damage in cellular environment which shields the nuclear DNA was higher than that in organism in apparent dose. So we use low UVB light as main study agent. Low dose UV-irradiated HDF-a cells (Human Dermal Fibroblasts-adult cells) which is weaker than epidermic cells were cultured with DMEM at different trace amount of Mg2+ (0mmol/L , 0.1mmol/L , 0.2mmol/L, 0.4mmol/L, 0.8mmol/L, 1.2mmol/L) free-serum DMEM and the repair of DNA strands injured were observed. Treat these cells with DNA strand breaks detection, photoproducts detection and the repair of photoproducts detection. Then quantitate the role of trace amount Mg2+ in repair of UV light-induced damage to human skin. The experiment results indicated that epidermic cells have capability of resistance to UV-radiation at a certain extent. And Mg2+ can regulate the UV-induced damage repair and relative vitality. It can offer a rationale and experiment data to relieve UV light-induced skin disease.

Ultraviolet radiation, human health, and the urban forest

Treesearch

Gordon M. Heisler; Richard H. Grant

2000-01-01

Excess exposure to ultraviolet (UV) radiation from the sun, particularly the ultraviolet B (UVB) portion, has been linked with adverse effects on human health ranging from skin cancers to eye diseases such as cataracts. Trees may prevent even greater disease rates in humans by reducing UV exposure. Tree shade greatly reduces UV irradiance when both the sun and sky are...

Exposure of DNA bases induced by the interaction of DNA and calf thymus DNA helix-destabilizing protein.

PubMed Central

Kohwi-Shigematsu, T; Enomoto, T; Yamada, M A; Nakanishi, M; Tsuboi, M

1978-01-01

The reaction of chloroacetaldehyde with adenine bases in DNA to give a fluorescent product was used to study the availability to intermolecular reaction of positions 1 and 6 of adenine in DNA complexes with calf thymus DNA helix-destabilizing protein. No inhibition of this reaction was observed when heat-denatured DNA was complexed with the protein at a protein/DNA weight ratio of 10:1, compared to free DNA. On the contrary, the same reaction was inhibited markedly for denatured DNA in the presence of calf thymus histone HI at protein/DNA weight ratio of 2:1. Furthermore, the exchange rate for hydrogens of amino and imide groups of DNA bases in DNA strands with deuterium in the solvent was totally unaffected upon complexing of DNA with the DNA helix-destabilizing protein as examined by stopped-flow ultraviolet spectroscopy. These results indicate that the DNA helix-destabilizing protein forms a complex with single-stranded DNA, leaving DNA bases uncovered by the protein. The fluorescence intensity of DNA pretreated with chloroacetaldehyde was amplified by nearly 3-fold upon addition of the DNA helix-destabilizing protein. The possibility of "unstacking" of DNA bases induced by the protein is discussed. PMID:216994

Ultraviolet-induced movement of the human DNA repair protein, xeroderma pigmentosum type G, in the nucleus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, M.S.; Knauf, J.A.; Pendergrass, S.H.

1996-08-06

Xeroderma pigmentosum type G (XPG) is a human genetic disease exhibiting extreme sensitivity to sunlight. XPG patients are defective XPG endonuclease, which is an enzyme essential for DNA repair of the major kinds of solar ultraviolet (UV)-induced DNA damages. Here we describe a novel dynamics of this protein within the cell nucleus after UV irradiation of human cells. USing confocal microscopy, we have localized the immunofluorescent, antigenic signal of XPG protein to foci throughout the cell nucleus. Our biochemical studies also established that XPG protein forms a tight association with nuclear structure(s). In human skin fibroblast cells, the number ofmore » XPG foci decreased within 2 h after UV irradiation, whereas total nuclear XPG fluorescence intensity remained constant, suggesting redistribution of XPG from a limited number of nuclear foci to the nucleus overall. Within 8 h after UV, most XPG antigenic signal was found as foci. Using {beta}-galactosidase-XPG fusion constructs ({beta}-gal-XPG) transfected into HeLa cells, we have identified a single region of XPG that is evidently responsible both for foci formation and for the UV dynamic response. The fusion protein carrying the C terminus of XPG (amino acids 1146-1185) localized {beta}-gal specific antigenic signal to foci and to the nucleolus regions. After UV irradiation, antigenic {beta}-gal translocated reversibly from the subnuclear structures to the whole nucleus with kinetics very similar to the movements of XPG protein. These findings lead us to propose a model in which distribution of XPG protein may regulate the rate of DNA repair within transcriptionally active and inactive compartments of the cell nucleus. 50 refs., 5 figs., 1 tab.« less

In situ gene expression profiling of the thermoacidophilic alga Cyanidioschyzon in relation to visible and ultraviolet irradiance.

PubMed

Skorupa, Dana J; Castenholz, Richard W; Mazurie, Aurélien; Carey, Charles; Rosenzweig, Frank; McDermott, Timothy R

2014-06-01

Ultraviolet and high-intensity visible radiation generate reactive intermediates that damage phototrophic microorganisms. In Yellowstone National Park, the thermoacidophilic alga Cyanidioschyzon exhibits an annual seasonal biomass fluctuation referred to as 'mat decline', where algal viability decreases as ultraviolet and visible irradiances increase during summer. We examined the role irradiance might play in mat decline using irradiance filters that uncouple ultraviolet and visible effects along with custom microarrays to study gene expression in situ. Of the 6507 genes, 88% showed no response to ultraviolet or visible, implying that at the biomolecular level, these algae inhabit a chemostat-like environment and is consistent with the near constant aqueous chemistry measured. The remaining genes exhibited expression changes linked to ultraviolet exposure, to increased visible radiation, or to the apparent combined effects of ultraviolet and visible. Expression of DNA repetitive elements was synchronized, being repressed by visible but also influenced by ultraviolet. At highest irradiance levels, these algae reduced transcription of genes encoding functions involved with DNA replication, photosynthesis and cell cycle progression but exhibited an uptick in activities related to repairing DNA damage. This corroborates known physiological responses to ultraviolet and visible radiation, and leads us to provisionally conclude that mat decline is linked to photoinhibition. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

Understanding the Early Evolution of M dwarf Extreme Ultraviolet Radiation

NASA Astrophysics Data System (ADS)

Peacock, Sarah; Barman, Travis; Shkolnik, Evgenya

2015-11-01

The chemistry and evolution of planetary atmospheres depends on the evolution of high-energy radiation emitted by its host star. High levels of extreme ultraviolet (EUV) radiation can drastically alter the atmospheres of terrestrial planets through ionizing, heating, expanding, chemically modifying and eroding them during the first few billion years of a planetary lifetime. While there is evidence that stars emit their highest levels of far and near ultraviolet (FUV; NUV) radiation in the earliest stages of their evolution, we are currently unable to directly measure the EUV radiation. Most previous stellar atmosphere models under-predict FUV and EUV emission from M dwarfs; here we present new models for M stars that include prescriptions for the hot, lowest density atmospheric layers (chromosphere, transition region and corona), from which this radiation is emitted. By comparing our model spectra to GALEX near and far ultraviolet fluxes, we are able to predict the evolution of EUV radiation for M dwarfs from 10 Myr to a few Gyr. This research is the next major step in the HAZMAT (HAbitable Zones and M dwarf Activity across Time) project to analyze how the habitable zone evolves with the evolving properties of stellar and planetary atmospheres.

Solar ultraviolet radiation from cancer induction to cancer prevention: solar ultraviolet radiation and cell biology.

PubMed

Tuorkey, Muobarak J

2015-09-01

Although decades have elapsed, researchers still debate the benefits and hazards of solar ultraviolet radiation (UVR) exposure. On the one hand, humans derive most of their serum 25-hydroxycholecalciferol [25(OH)D3], which has potent anticancer activity, from solar UVB radiation. On the other hand, people are more aware of the risk of cancer incidence associated with harmful levels of solar UVR from daily sunlight exposure. Epidemiological data strongly implicate UV radiation exposure as a major cause of melanoma and other cancers, as UVR promotes mutations in oncogenes and tumor-suppressor genes. This review highlights the impact of the different mutagenic effects of solar UVR, along with the cellular and carcinogenic challenges with respect to sun exposure.

Low intensity microwave radiation induced oxidative stress, inflammatory response and DNA damage in rat brain.

PubMed

Megha, Kanu; Deshmukh, Pravin Suryakantrao; Banerjee, Basu Dev; Tripathi, Ashok Kumar; Ahmed, Rafat; Abegaonkar, Mahesh Pandurang

2015-12-01

Over the past decade people have been constantly exposed to microwave radiation mainly from wireless communication devices used in day to day life. Therefore, the concerns over potential adverse effects of microwave radiation on human health are increasing. Until now no study has been proposed to investigate the underlying causes of genotoxic effects induced by low intensity microwave exposure. Thus, the present study was undertaken to determine the influence of low intensity microwave radiation on oxidative stress, inflammatory response and DNA damage in rat brain. The study was carried out on 24 male Fischer 344 rats, randomly divided into four groups (n=6 in each group): group I consisted of sham exposed (control) rats, group II-IV consisted of rats exposed to microwave radiation at frequencies 900, 1800 and 2450 MHz, specific absorption rates (SARs) 0.59, 0.58 and 0.66 mW/kg, respectively in gigahertz transverse electromagnetic (GTEM) cell for 60 days (2h/day, 5 days/week). Rats were sacrificed and decapitated to isolate hippocampus at the end of the exposure duration. Low intensity microwave exposure resulted in a frequency dependent significant increase in oxidative stress markers viz. malondialdehyde (MDA), protein carbonyl (PCO) and catalase (CAT) in microwave exposed groups in comparison to sham exposed group (p<0.05). Whereas, levels of reduced glutathione (GSH) and superoxide dismutase (SOD) were found significantly decreased in microwave exposed groups (p<0.05). A significant increase in levels of pro-inflammatory cytokines (IL-2, IL-6, TNF-α, and IFN-γ) was observed in microwave exposed animal (p<0.05). Furthermore, significant DNA damage was also observed in microwave exposed groups as compared to their corresponding values in sham exposed group (p<0.05). In conclusion, the present study suggests that low intensity microwave radiation induces oxidative stress, inflammatory response and DNA damage in brain by exerting a frequency dependent effect

Celecoxib Induced Tumor Cell Radiosensitization by Inhibiting Radiation Induced Nuclear EGFR Transport and DNA-Repair: A COX-2 Independent Mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dittmann, Klaus H.; Mayer, Claus; Ohneseit, Petra A.

2008-01-01

Purpose: The purpose of the study was to elucidate the molecular mechanisms mediating radiosensitization of human tumor cells by the selective cyclooxygenase (COX)-2 inhibitor celecoxib. Methods and Materials: Experiments were performed using bronchial carcinoma cells A549, transformed fibroblasts HH4dd, the FaDu head-and-neck tumor cells, the colon carcinoma cells HCT116, and normal fibroblasts HSF7. Effects of celecoxib treatment were assessed by clonogenic cell survival, Western analysis, and quantification of residual DNA damage by {gamma}H{sub 2}AX foci assay. Results: Celecoxib treatment resulted in a pronounced radiosensitization of A549, HCT116, and HSF7 cells, whereas FaDu and HH4dd cells were not radiosensitized. The observedmore » radiosensitization could neither be correlated with basal COX-2 expression pattern nor with basal production of prostaglandin E2, but was depended on the ability of celecoxib to inhibit basal and radiation-induced nuclear transport of epidermal growth factor receptor (EGFR). The nuclear EGFR transport was strongly inhibited in A549-, HSF7-, and COX-2-deficient HCT116 cells, which were radiosensitized, but not in FaDu and HH4dd cells, which resisted celecoxib-induced radiosensitization. Celecoxib inhibited radiation-induced DNA-PK activation in A549, HSF7, and HCT116 cells, but not in FaDu and HH4dd cells. Consequentially, celecoxib increased residual {gamma}H2AX foci after irradiation, demonstrating that inhibition of DNA repair has occurred in responsive A549, HCT116, and HSF7 cells only. Conclusions: Celecoxib enhanced radiosensitivity by inhibition of EGFR-mediated mechanisms of radioresistance, a signaling that was independent of COX-2 activity. This novel observation may have therapeutic implications such that COX-2 inhibitors may improve therapeutic efficacy of radiation even in patients whose tumor radioresistance is not dependent on COX-2.« less

Interactions of Changing Solar Ultraviolet Radiation and Climate with Light Induced Chemical Reactions in Aquatic Environments

EPA Science Inventory

Changes in the ozone layer over the past two decades have resulted in increases in solar ultraviolet radiation that reach the surface of North American aquatic environments. Concurrent changes in atmospheric CO2 are resulting in changes in stratification and precipitation that ar...

Ultraviolet radiation accelerates BRAF-driven melanomagenesis by targeting TP53

PubMed Central

Rae, Joel; Hogan, Kate; Ejiama, Sarah; Girotti, Maria Romina; Cook, Martin; Dhomen, Nathalie; Marais, Richard

2014-01-01

Cutaneous melanoma is epidemiologically linked to ultraviolet radiation (UVR), but the molecular mechanisms by which UVR drives melanomagenesis remain unclear1,2. The most common somatic mutation in melanoma is a V600E substitution in BRAF, which is an early event3. To investigate how UVR accelerates oncogenic BRAF-driven melanomagenesis, we used a V600EBRAF mouse model. In mice expressing V600EBRAF in their melanocytes, a single dose of UVR that mimicked mild sunburn in humans induced clonal expansion of the melanocytes, and repeated doses of UVR increased melanoma burden. We show that sunscreen (UVA superior: UVB SPF50) delayed the onset of UVR-driven melanoma, but only provided partial protection. The UVR-exposed tumours presented increased numbers of single nucleotide variants (SNVs) and we observed mutations (H39Y, S124F, R245C, R270C, C272G) in the Trp53 tumour suppressor in ~40% of cases. TP53 is an accepted UVR target in non-melanoma skin cancer, but is not thought to play a major role in melanoma4. However, we show that mutant Trp53 accelerated V600EBRAF-driven melanomagenesis and that TP53 mutations are linked to evidence of UVR-induced DNA damage in human melanoma. Thus, we provide mechanistic insight into epidemiological data linking UVR to acquired naevi in humans5. We identify TP53/Trp53 as a UVR-target gene that cooperates with V600EBRAF to induce melanoma, providing molecular insight into how UVR accelerates melanomagenesis. Our study validates public health campaigns that promote sunscreen protection for individuals at risk of melanoma. PMID:24919155

Feasibility of Ionization-Mediated Pathway for Ultraviolet-Induced Melanin Damage.

PubMed

Mandal, Mukunda; Das, Tamal; Grewal, Baljinder K; Ghosh, Debashree

2015-10-22

Melanin is the pigment found in human skin that is responsible for both photoprotection and photodamage. Recently there have been reports that greater photodamage of DNA occurs when cells containing melanin are irradiated with ultraviolet (UV) radiation, thus suggesting that the photoproducts of melanin cause DNA damage. Photoionization processes have also been implicated in the photodegradation of melanin. However, not much is known about the oxidation potential of melanin and its monomers. In this work we calculate the ionization energies of monomers, dimers, and few oligomers of eumelanin to estimate the threshold energy required for the ionization of eumelanin. We find that this threshold is within the UV-B region for eumelanin. We also look at the charge and spin distributions of the various ionized states of the monomers that are formed to understand which of the ionization channels might favor monomerization from a covalent dimer.

Nanotherapy of cancer by photoelectrons emitted from the surface of nanoparticles exposed to nonionizing ultraviolet radiation.

PubMed

Letfullin, Renat R; George, Thomas F

2017-05-01

We introduce a new method for selectively destroying cancer cell organelles by electrons emitted from the surface of intracellularly localized nanoparticles exposed to the nonionizing ultraviolet (UV) radiation. We propose to target cancerous intracellular organelles by nanoparticles and expose them to UV radiation with energy density safe for healthy tissue. We simulate the number of photoelectrons produced by the nanoparticles made of various metals and radii, calculate their kinetic energy and compare it to the threshold energy for producing biological damage. Exposure of metal nanoparticles to UV radiation generates photoelectrons with kinetic energies up to 11 eV, which is high enough to produce single- to double-strand breaks in the DNA and damage the cancerous cell organelles.

Effects of ultraviolet radiation on lattice imperfections in pyrolytic boron nitride.

NASA Technical Reports Server (NTRS)

Buckley, J. D.; Cooley, J. A.

1971-01-01

Pyrolitic boron nitride was exposed to 310 equivalent sun hours of ultraviolet radiation in a space environment simulator with the objective to evaluate its applicability as a pigment for a thermal control coating and to identify radiation damage using X-ray diffraction techniques. Lattice parameter comparisons show a definite increase in lattice imperfections in the crystal structure resulting from the ultraviolet irradiation. This sensitivity to radiation damage makes pyrolitic boron nitride unsuitable as a pigment for thermal control coating.

Long-term effects of inducible mutagenic DNA repair on relative fitness and phenotypic diversification in Pseudomonas cichorii 302959.

PubMed

Weigand, Michael R; Sundin, George W

2009-01-01

Mutagenic DNA repair (MDR) employs low-fidelity DNA polymerases capable of replicating past DNA lesions resulting from exposure to high-energy ultraviolet radiation (UVR). MDR confers UVR tolerance and activation initiates a transient mutator phenotype that may provide opportunities for adaptation. To investigate the potential role of MDR in adaptation, we have propagated parallel lineages of the highly mutable epiphytic plant pathogen Pseudomonas cichorii 302959 with daily UVR activation (UVR lineages) for approximately 500 generations. Here we examine those lineages through the measurement of relative fitness and observation of distinct colony morphotypes that emerged. Isolates and population samples from UVR lineages displayed gains in fitness relative to the ancestor despite increased rates of inducible mutation to rifampicin resistance. Regular activation of MDR resulted in the maintenance of genetic diversity within UVR lineages, including the reproducible diversification and coexistence of "round" and "fuzzy" colony morphotypes. These results suggest that inducible mutability may present a reasonable strategy for adaptive evolution in stressful environments by contributing to gains in relative fitness and diversification.

Ultraviolet radiation exposure triggers neurokinin-1 receptor upregulation in ocular tissues in vivo.

PubMed

Gross, Janine; Wegener, Alfred R; Kronschlaeger, Martin; Holz, Frank G; Schönfeld, Carl-Ludwig; Meyer, Linda M

2018-04-26

The purpose of this study was to investigate the neurokinin receptor-1 (NKR-1) protein expression in ocular tissues before and after supra-cataract threshold ultraviolet radiation (UVR-B peak at 312 nm) exposure in vivo in a mouse model. Six-week-old C57Bl/6 mice were unilaterally exposed to a single (2.9 kJ/m 2 ) and an above 3-fold UVR-B cataract threshold dose (9.4 kJ/m 2 ) of UVR. UVR-exposure (λpeak = 312 nm) was performed in mydriasis using a Bio-Spectra exposure system. After latency periods of 3 and 7 days, eyes were fixed in 4% paraformaldehyde, embedded in paraffin, sectioned and stained with fluorescence coupled antibody for NKR-1 and DAPI for cell nuclei staining. Control animals received only anesthesia but no UVR-exposure. Cataract development was documented with a Leica dark-field microscope and quantified as integrated optical density (IOD). NKR-1 is ubiquitously present in ocular tissues. An above 3-fold cataract threshold dose of UV-radiation induced NKR-1 upregulation after days 3 and 7 in the epithelium and endothelium of the cornea, the endothelial cells of the iris vessels, the pigmented epithelium/stroma of the ciliary body, the lens epithelium, pronounced in the nuclear bow region and the inner plexiform layer of the retina. A significant upregulation of NKR-1 could not be provoked with a single cataract threshold dose (2.9 kJ/m 2 UVR-B) ultraviolet irradiation. All exposed eyes developed anterior subcapsular cataracts. Neurokinin-1 receptor is present ubiquitously in ocular tissues including the lens epithelium and the nuclear bow region of the lens. UV-radiation exposure to an above 3-fold UVR-B cataract threshold dose triggers NKR-1 upregulation in the eye in vivo. The involvement of inflammation in ultraviolet radiation induced cataract and the role of neuroinflammatory peptides such as substance P and its receptor, NKR-1, might have been underestimated to date. Copyright © 2018. Published by Elsevier Ltd.

Ultraviolet laser beam monitor using radiation responsive crystals

DOEpatents

McCann, Michael P.; Chen, Chung H.

1988-01-01

An apparatus and method for monitoring an ultraviolet laser beam includes disposing in the path of an ultraviolet laser beam a substantially transparent crystal that will produce a color pattern in response to ultraviolet radiation. The crystal is exposed to the ultraviolet laser beam and a color pattern is produced within the crystal corresponding to the laser beam intensity distribution therein. The crystal is then exposed to visible light, and the color pattern is observed by means of the visible light to determine the characteristics of the laser beam that passed through crystal. In this manner, a perpendicular cross sectional intensity profile and a longitudinal intensity profile of the ultraviolet laser beam may be determined. The observation of the color pattern may be made with forward or back scattered light and may be made with the naked eye or with optical systems such as microscopes and television cameras.

The effect of prescription eyewear on ocular exposure to ultraviolet radiation.

PubMed Central

Rosenthal, F S; Bakalian, A E; Taylor, H R

1986-01-01

Several studies have suggested that ultraviolet radiation in sunlight may cause cataracts and other eye disease. We evaluated the effect of prescription eyewear in attenuating ocular exposure to ultraviolet radiation (UVR) in the sunlight portions of the ultraviolet spectrum (295-350 nm). Using natural sunlight as the source, the attenuation was measured with two ultraviolet detectors, one sensitive to only UVB (295-315 nm) and one sensitive to both UVA and UVB (295-350 nm). A random sample of spectacles, spectacle lenses, and contact lenses was examined. The average transmission, as measured with either detector, was highest for soft contact lenses, followed by glass spectacle lenses, untinted hard contact lenses, and plastic spectacle lenses. Measurements performed with mannikins wearing spectacles showed that an average of 6.6 per cent of incident radiation reached the eye even when the lenses were covered with black opaque tape. The amount of exposure was increased substantially when the spectacles were moved 0.6 cm away from the forehead. The results show that the protection against ultraviolet exposure provided by prescription eyewear is highly variable and depends largely on its composition, size, and wearing position. PMID:3752323

Tryptophan Cluster Protects Human γD-Crystallin from Ultraviolet Radiation-Induced Photoaggregation In Vitro

PubMed Central

Schafheimer, Nathaniel; King, Jonathan

2013-01-01

Exposure to ultraviolet radiation (UVR) is a significant risk factor for age-related cataract, a disease of the human lens and the most prevalent cause of blindness in the world. Cataract pathology involves protein misfolding and aggregation of the primary proteins of the lens, the crystallins. Human γD-crystallin (HγD-Crys) is a major γ-crystallin in the nucleus of the human lens. We report here analysis of UVR-induced damage to HγD-Crys in vitro. Irradiation of solutions of recombinant HγD-Crys with UVA/UVB light produced a rise in solution turbidity due to polymerization of the monomeric crystallins into higher molecular weight aggregates. A significant fraction of this polymerized protein was covalently linked. Photoaggregation of HγD-Crys required oxygen and its rate was protein concentration and UVR dose dependent. To investigate the potential roles of individual tryptophan residues in photoaggregation, triple W:F mutants of HγD-Crys were irradiated. Surprisingly, despite reducing UVR absorbing capacity, multiple W:F HγD-Crys mutant proteins photoaggregated more quickly and extensively than wild type. The results reported here are consistent with previous studies that postulated that an energy transfer mechanism between the highly conserved pairs of tryptophan residues in HγD-Crys could be protective against UVR-induced photodamage. PMID:23683003

Ultraviolet radiation directly induces pigment production by cultured human melanocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Friedmann, P.S.; Gilchrest, B.A.

1987-10-01

In humans the major stimulus for cutaneous pigmentation is ultraviolet radiation (UVR). Little is known about the mechanism underlying this response, in part because of the complexity of interactions in whole epidermis. Using a recently developed culture system, human melanocytes were exposed daily to a physiologic range of UVR doses from a solar simulator. Responses were determined 24 hours after the last exposure. There was a dose-related increase in melanin content per cell and uptake of /sup 14/C-DOPA, accompanied by growth inhibition. Cells from donors of different racial origin gave proportionately similar increases in melanin, although there were approximately tenfoldmore » differences in basal values. Light and electron microscopy revealed UVR-stimulated increases in dendricity as well as melanosome number and degree of melanization, analogous to the well-recognized melanocyte changes following sun exposure of intact skin. Similar responses were seen with Cloudman S91 melanoma cells, although this murine cell line required lower UVR dosages and fewer exposures for maximal stimulation. These data establish that UVR is capable of directly stimulating melanogenesis. Because cyclic AMP elevation has been associated in some settings with increased pigment production by cultured melanocytes, preliminary experiments were conducted to see if the effects of UVR were mediated by cAMP. Both alpha-MSH and isobutylmethylxanthine (IBMX), as positive controls, caused a fourfold increase in cAMP level in human melanocytes and/or S91 cells, but following a dose of UVR sufficient to stimulate pigment production there was no change in cAMP level up to 4 hours after exposure. Thus, it appears that the UVR-induced melanogenesis is mediated by cAMP-independent mechanisms.« less

RuvAB and RecG are not essential for the recovery of DNA synthesis following UV-induced DNA damage in Escherichia coli.

PubMed Central

Donaldson, Janet R; Courcelle, Charmain T; Courcelle, Justin

2004-01-01

Ultraviolet light induces DNA lesions that block the progression of the replication machinery. Several models speculate that the resumption of replication following disruption by UV-induced DNA damage requires regression of the nascent DNA or migration of the replication machinery away from the blocking lesion to allow repair or bypass of the lesion to occur. Both RuvAB and RecG catalyze branch migration of three- and four-stranded DNA junctions in vitro and are proposed to catalyze fork regression in vivo. To examine this possibility, we characterized the recovery of DNA synthesis in ruvAB and recG mutants. We found that in the absence of either RecG or RuvAB, arrested replication forks are maintained and DNA synthesis is resumed with kinetics that are similar to those in wild-type cells. The data presented here indicate that RecG- or RuvAB-catalyzed fork regression is not essential for DNA synthesis to resume following arrest by UV-induced DNA damage in vivo. PMID:15126385

Influence of tropospheric ozone control on exposure to ultraviolet radiation at the surface.

PubMed

Madronich, Sasha; Wagner, Mark; Groth, Philip

2011-08-15

Improving air quality by reducing ambient ozone (O(3)) will likely lower O(3) concentrations throughout the troposphere and increase the transmission of solar ultraviolet (UV) radiation to the surface. The changes in surface UV radiation between two control scenarios (nominally 84 and 70 ppb O(3) for summer 2020) in the Eastern two-thirds of the contiguous U.S. are estimated, using tropospheric O(3) profiles calculated with a chemistry-transport model (Community Multi-Scale Air Quality, CMAQ) as inputs to a detailed model of the transfer of solar radiation through the atmosphere (tropospheric ultraviolet-visible, TUV) for clear skies, weighed for the wavelengths known to induce sunburn and skin cancer. Because the incremental emission controls differ according to region, strong spatial variability in O(3) reductions and in corresponding UV radiation increments is seen. The geographically averaged UV increase is 0.11 ± 0.03%, whereas the population-weighted increase is larger, 0.19 ± 0.06%, because O(3) reductions are greater in more densely populated regions. These relative increments in exposure are non-negligible given the already high incidence of UV-related health effects, but are lower by an order of magnitude or more than previous estimates.

PTEN positively regulates UVB-induced DNA damage repair

PubMed Central

Ming, Mei; Feng, Li; Shea, Christopher R.; Soltani, Keyoumars; Zhao, Baozhong; Han, Weinong; Smart, Robert C.; Trempus, Carol S.; He, Yu-Ying

2011-01-01

Non-melanoma skin cancer is the most common cancer in the U.S., where DNA-damaging UVB radiation from the sun remains the major environmental risk factor. However, the critical genetic targets of UVB radiation are undefined. Here we show that attenuating PTEN in epidermal keratinocytes is a predisposing factor for UVB-induced skin carcinogenesis in mice. In skin papilloma and squamous cell carcinoma (SCC), levels of PTEN were reduced compared to skin lacking these lesions. Likewise, there was a reduction in PTEN levels in human premalignant actinic keratosis and malignant SCC, supporting a key role for PTEN in human skin cancer formation and progression. PTEN downregulation impaired the capacity of global genomic nucleotide excision repair (GG-NER), a critical mechanism for removing UVB-induced mutagenic DNA lesions. In contrast to the response to ionizing radiation, PTEN downregulation prolonged UVB-induced growth arrest and increased the activation of the Chk1 DNA damage pathway in an AKT-independent manner, likely due to reduced DNA repair. PTEN loss also suppressed expression of the key GG-NER protein xeroderma pigmentosum C (XPC) through the AKT/p38 signaling axis. Reconstitution of XPC levels in PTEN-inhibited cells restored GG-NER capacity. Taken together, our findings define PTEN as an essential genomic gatekeeper in the skin, through its ability to positively regulate XPC-dependent GG-NER following DNA damage. PMID:21771908

DEMONSTRATION BULLETIN - ULTROX INTERNATIONAL, INC. ULTRAVIOLET RADIATION AND OXIDATION

EPA Science Inventory

The ultraviolet (UV) radiation/oxidation treatment technology developed by Ultrox International uses a combination of UV radiation, ozone, and hydrogen peroxide to oxidize organic compounds in water. Various operating parameters can be adjusted in the Ultrox® system to enhan...

Mechanism of growth delay induced in Escherichia coli by near ultraviolet radiation.

PubMed Central

Ramabhadran, T V; Jagger, J

1976-01-01

Continuously growing cultures of E. coli B/r were irradiated with a fluence of broad-band near-ultraviolet radiation (315-405 nm) sufficient to cause extensive growth delay and complete cessation of net RNA synthesis. Chloramphenicol treatment was found to stimulate resumption of RNA synthesis, similar to that observed with chloramphenicol treatment after amino-acid starvation. E. coli strains in which amino-acid starvation does not result in cessation of RNA synthesis ("relaxed" or rel- strains) show no cessation of growth and only a slight effect on the rate of growth or of RNA synthesis. These findings show that such near-UV fluences do not inactivate the RNA synthetic machinery but affect the regulation of RNA synthesis, in a manner similat to that produced by amino-acid starvation. Such regulation is believed to be mediated through alterations in concentration of guanosine tetraphosphate (ppGpp), and our estimations of ppGpp after near-UV irradiation are consistent with such an interpretation. These data, combined with earlier published data, strongly suggest that the mechanism of near-UV-induced growth delay in E. coli involves partial inactivation of certain tRNA species, which is interpreted by the cell in a manner similar to that of amino-acid starvation, causing a rise in ppGpp levels, a shut-off of net RNA synthesis, and the induction of a growth delay. Images PMID:1108019

Cloud effects on middle ultraviolet global radiation

NASA Technical Reports Server (NTRS)

Borkowski, J.; Chai, A.-T.; Mo, T.; Green, A. E. O.

1977-01-01

An Eppley radiometer and a Robertson-Berger sunburn meter are employed along with an all-sky camera setup to study cloud effects on middle ultraviolet global radiation at the ground level. Semiempirical equations to allow for cloud effects presented in previous work are compared with the experimental data. The study suggests a means of defining eigenvectors of cloud patterns and correlating them with the radiation at the ground level.

The Degree of Radiation-Induced DNA Strand Breaks Is Altered by Acute Sleep Deprivation and Psychological Stress and Is Associated with Cognitive Performance in Humans.

PubMed

Moreno-Villanueva, Maria; von Scheven, Gudrun; Feiveson, Alan; Bürkle, Alexander; Wu, Honglu; Goel, Namni

2018-03-27

Sleep deprivation is associated with impaired immune responses, cancer, and morbidity and mortality, and can degrade cognitive performance, although individual differences exist in such responses. Sleep deprivation induces DNA strand breaks and DNA base oxidation in animals, and psychological stress is associated with increased DNA damage in humans. It remains unknown whether sleep deprivation or psychological stress in humans affects DNA damage response from environmental stressors, and whether these responses predict cognitive performance during sleep deprivation. Sixteen healthy adults (ages 29-52;mean age±SD, 36.4±7.1 years;7 women) participated in a 5-day experiment involving two 8 hour time-in-bed [TIB] baseline nights, followed by 39 hours total sleep deprivation (TSD), and two 8-10 hour TIB recovery nights. A modified Trier Social Stress Test was conducted on the day after TSD. Psychomotor Vigilance Tests measured behavioral attention. DNA damage was assessed in blood cells collected at 5 time points, and blood cells were irradiated ex-vivo. TSD, alone or in combination with psychological stress, did not induce significant increases in DNA damage. By contrast, radiation-induced DNA damage decreased significantly in response to TSD, but increased back to baseline when combined with psychological stress. Cognitively-vulnerable individuals had more radiation-induced DNA strand breaks before TSD, indicating their greater sensitivity to DNA damage from environmental stressors. Our results provide novel insights into the molecular consequences of sleep deprivation, psychological stress, and performance vulnerability. They are important for situations involving sleep loss, radiation exposure and cognitive deficits, including cancer therapy, environmental toxicology, and space medicine.

Radiation Damage Effects in Far Ultraviolet Filters and Substrates

NASA Technical Reports Server (NTRS)

Keffer, Charles E.; Torr, Marsha R.; Zukic, Muamer; Spann, James F.; Torr, Douglas G.; Kim, Jongmin

1993-01-01

New advances in VUV thin film filter technology have been made using filter designs with multilayers of materials such as Al2O3, BaF2, CaF2, HfO2, LaF3, MgF2, and SiO2. Our immediate application for these filters will be in an imaging system to be flown on a satellite where a 2 X 9 R(sub E) orbit will expose the instrument to approximately 275 krads of radiation. In view of the fact that no previous studies have been made on potential radiation damage of these materials in the thin film format, we report on such an assessment here. Transmittances and reflectances of BaF2, CaF2, HfO2, LaF3, MgF2, and SiO2 thin films on MgF2 substrates, Al2O3 thin films on fused silica substrates, uncoated fused silica and MgF2, and four multilayer filters made from these materials were measured from 120 nm to 180 nm before and after irradiation by 250 krads from a Co-60 gamma radiation source. No radiation-induced losses in transmittance or reflectance occurred in this wavelength range. Additional postradiation measurements from 160 nm to 300 nm indicated a 3 - 5% radiation-induced absorption near 260 nm in some of the samples with MgF2 substrates. From these measurements it is concluded that far ultraviolet filters made from the materials tested should experience less that 5% change from exposure to up to 250 krads of high energy radiation in space applications.

Ultraviolet radiation induces dose-dependent pigment dispersion in crustacean chromatophores.

PubMed

Gouveia, Glauce Ribeiro; Lopes, Thaís Martins; Neves, Carla Amorim; Nery, Luiz Eduardo Maia; Trindade, Gilma Santos

2004-10-01

Pigment dispersion in chromatophores as a response to UV radiation was investigated in two species of crustaceans, the crab Chasmagnathus granulata and the shrimp Palaemonetes argentinus. Eyestalkless crabs and shrimps maintained on either a black or a white background were irradiated with different UV bands. In eyestalkless crabs the significant minimal effective dose inducing pigment dispersion was 0.42 J/cm(2) for UVA and 2.15 J/cm(2) for UVB. Maximal response was achieved with 10.0 J/cm(2) UVA and 8.6 J/cm(2) UVB. UVA was more effective than UVB in inducing pigment dispersion. Soon after UV exposure, melanophores once again reached the initial stage of pigment aggregation after 45 min. Aggregated erythrophores of shrimps adapted to a white background showed significant pigment dispersion with 2.5 J/cm(2) UVA and 0.29 J/cm(2) UVC. Dispersed erythrophores of shrimps adapted to a black background did not show any significant response to UVA, UVB or UVC radiation. UVB did not induce any significant pigment dispersion in shrimps adapted to either a white or a black background. As opposed to the tanning response, which only protects against future UV exposure, the pigment dispersion response could be an important agent protecting against the harmful effects of UV radiation exposure.

Solar ultraviolet radiation in a changing climate

EPA Science Inventory

The projected large increases in damaging ultraviolet radiation as a result of global emissions of ozone-depleting substances have been forestalled by the success of the Montreal Protocol. New challenges are now arising in relation to climate change. We highlight the complex inte...

Ultraweak photon emission induced by visible light and ultraviolet A radiation via photoactivated skin chromophores: in vivo charge coupled device imaging.

PubMed

Prasad, Ankush; Pospíšil, Pavel

2012-08-01

Solar radiation that reaches Earth's surface can have severe negative consequences for organisms. Both visible light and ultraviolet A (UVA) radiation are known to initiate the formation of reactive oxygen species (ROS) in human skin by photosensitization reactions (types I and II). In the present study, we investigated the role of visible light and UVA radiation in the generation of ROS on the dorsal and the palmar side of a hand. The ROS are known to oxidize biomolecules such as lipids, proteins, and nucleic acids to form electronically excited species, finally leading to ultraweak photon emission. We have employed a highly sensitive charge coupled device camera and a low-noise photomultiplier tube for detection of two-dimensional and one-dimensional ultraweak photon emission, respectively. Our experimental results show that oxidative stress is generated by the exposure of human skin to visible light and UVA radiation. The oxidative stress generated by UVA radiation is claimed to be significantly higher than that by visible light. Two-dimensional photon imaging can serve as a potential tool for monitoring the oxidative stress in the human skin induced by various stress factors irrespective of its physical or chemical nature.

The human intra-S checkpoint response to UVC-induced DNA damage.

PubMed

Kaufmann, William K

2010-05-01

The intra-S checkpoint response to 254 nm light (UVC)-induced DNA damage appears to have dual functions to slow the rate of DNA synthesis and stabilize replication forks that become stalled at sites of UVC-induced photoproducts in DNA. These functions should provide more time for repair of damaged DNA before its replication and thereby reduce the frequencies of mutations and chromosomal aberrations in surviving cells. This review tries to summarize the history of discovery of the checkpoint, the current state of understanding of the biological features of intra-S checkpoint signaling and its mechanisms of action with a focus primarily on intra-S checkpoint responses in human cells. The differences in the intra-S checkpoint responses to UVC and ionizing radiation-induced DNA damage are emphasized. Evidence that [6-4]pyrimidine-pyrimidone photoproducts in DNA trigger the response is discussed and the relationships between cellular responses to UVC and the molecular dose of UVC-induced DNA damage are briefly summarized. The role of the intra-S checkpoint response in protecting against solar radiation carcinogenesis remains to be determined.

Methylglyoxal-bis(guanylhydrazone), a polyamine analogue, sensitized γ-radiation-induced cell death in HL-60 leukemia cells Sensitizing effect of MGBG on γ-radiation-induced cell death.

PubMed

Kim, Jin Sik; Lee, Jin; Chung, Hai Won; Choi, Han; Paik, Sang Gi; Kim, In Gyu

2006-09-01

Methylglyoxal-bis(guanylhydrazone) (MGBG), a polyamine analogue, has been known to inhibit the biosynthesis of polyamines, which are important in cell proliferation. We showed that MGBG treatment significantly affected γ-radiation-induced cell cycle transition (G(1)/G(0)→S→G(2)/M) and thus γ-radiation-induced cell death. As determined by micronuclei and comet assay, we showed that it sensitized the cytotoxic effect induced by γ-radiation. One of the reasons is that polyamine depletion by MGBG treatment did not effectively protect against the chemical (OH) or physical damage to DNA caused by γ-radiation. Through in vitro experiment, we confirmed that DNA strand breaks induced by γ-radiation was prevented more effectively in the presence of polyamines (spermine and spermidine) than in the absence of polyamines. MGBG also blocks the cell cycle transition caused by γ-radiation (G(2) arrest), which helps protect cells by allowing time for DNA repair before entry into mitosis or apoptosis, via the down regulation of cyclin D1, which mediates the transition from G(1) to S phase of cell cycle, and ataxia telangiectasia mutated, which is involved in the DNA sensing, repair and cell cycle check point. Therefore, the abrogation of G(2) arrest sensitizes cells to the effect of γ-radiation. As a result, γ-radiation-induced cell death increased by about 2.5-3.0-fold in cells treated with MGBG. However, exogenous spermidine supplement partially relieved this γ-radiation-induced cytotoxicity and cell death. These findings suggest a potentially therapeutic strategy for increasing the cytotoxic efficacy of γ-radiation.

Assessment of the impact of increased solar ultraviolet radiation upon marine ecosystems

NASA Technical Reports Server (NTRS)

Worrest, R. C.; Vandyke, H.

1978-01-01

Reduction of the earth's ozone layer, with a resultant increase in transmission of solar ultraviolet radiation in the 290 to 320nm waveband (UV-B), via space shuttle operations through the stratosphere is considered. It is shown that simulated solar ultraviolet radiation can, under experimental conditions, detrimentally affect the marine organisms that form the base of the food web of oceanic and estuarine ecosystems. Whether a small increase in biologically harmful ultraviolet radiation might overwhelm these mechanisms and produce changes that will have damaging consequences to the biosphere is discussed. The potential for irreversible damage to the productivity, structure and/or functioning of a model estuarine ecosystem by increased UV-B radiation and whether these ecosystems are highly stable or amenable to adaptive change is studied. Data are provided to assess the potential impact upon marine ecosystems if space shuttle operations contribute to a reduction of the stratospheric ozone layer and the sensitivity of key community components to increased UV-B radiation is examined.

Ultraviolet-B radiation and the immune response of rainbow trout: Chapter 18

USGS Publications Warehouse

Fabacher, David L.; Little, Edward E.; Jones, S.B.; DeFabo, E.C.; Webber, L.J.; Stolen, Joanne S.; Fletcher, Thelma C.

1994-01-01

As part of a larger study on global climate change and ozone depletion we are investigating the effects of ultraviolet-B (UVB) radiation on fishes. We conducted a number of experiments to explore the possible effects of UVB radiation on the immune response of juvenile rainbow trout Oncorhynchus mykiss. In one study, the fish developed sunburn and fungal infection on the dorsal skin after exposure to levels of UVB that simulated ambient solar UVB levels observed at mid-latitudes. In a separate study, UVB-exposed rainbow trout with surgically administered dorsal lesions developed fungal infection on the lesions and surrounding skin. Many of these fish subsequently died within a 9 day exposure period. Fish with surgical lesions, but not exposed to UVB radiation, did not develop fungal infection and did not die. In mammals, UVB-induced immunosuppression is thought to occur through the isomerization of urocanic acid or the formation of DNA pyrimidine dimers, or through some interaction between the two. We found a substance that appeared, upon HPLC detection, to be trans-urocanic acid in the skin of UVB-exposed and unexposed rainbow trout. Neurotransmitter stimulation of adrenoceptors may be involved in changes in pigmentation observed in UVB-exposed fishes. We measured adrenoceptors in skin membranes from rainbow trout exposed to UVB and found a decrease in cz2-adrenoceptors compared with fish not exposed to UVB. Results of our study indicate that prolonged exposure of juvenile rainbow trout to mid-latitude levels of solar UVB may play an important role in the initiation of certain disease outbreaks and may decrease survival of fish that have lesions on the dorsal skin.

Establishing a ultraviolet radiation observational network and enhancing the study on ultraviolet radiation

NASA Astrophysics Data System (ADS)

Bai, Jianhui; Wang, Gengchen

2003-09-01

On the basis of analyzing observational data on solar radiation, meteorological parameters, and total ozone amount for the period of January 1990 to December 1991 in the Beijing area, an empirical calculation method for ultraviolet radiation (UV) in clear sky is obtained. The results show that the calculated values agree well with the observed, with maximum relative bias of 6.2% and mean relative bias for 24 months of 1.9%. Good results are also obtained when this method is applied in Guangzhou and Mohe districts. The long-term variation of UV radiation in clear sky over the Beijing area from 1979 to 1998 is calculated, and the UV variation trends and causes are discussed: direct and indirect UV energy absorption by increasing pollutants in the troposphere may have caused the UV decrease in clear sky in the last 20 years. With the enhancement of people’s quality of life and awareness of health, it will be valuable and practical to provid UV forecasts for typical cities and rural areas. So, we should develop and enhance UV study in systematic monitoring, forecasting, and developing a good and feasible method for UV radiation reporting in China, especially for big cities.

Ferulic acid (FA) abrogates γ-radiation induced oxidative stress and DNA damage by up-regulating nuclear translocation of Nrf2 and activation of NHEJ pathway.

PubMed

Das, Ujjal; Manna, Krishnendu; Khan, Amitava; Sinha, Mahuya; Biswas, Sushobhan; Sengupta, Aaveri; Chakraborty, Anindita; Dey, Sanjit

2017-01-01

The present study was aimed to evaluate the radioprotective effect of ferulic acid (FA), a naturally occurring plant flavonoid in terms of DNA damage and damage related alterations of repair pathways by gamma radiation. FA was administered at a dose of 50 mg/kg body weight for five consecutive days prior to exposing the swiss albino mice to a single dose of 10 Gy gamma radiation. Ionising radiation induces oxidative damage manifested by decreased expression of Cu, Zn-SOD (SOD stands for super oxide dismutase), Mn-SOD and catalase. Gamma radiation promulgated reactive oxygen species (ROS) mediated DNA damage and modified repair pathways. ROS enhanced nuclear translocation of p53, activated ATM (ataxia telangiectasia-mutated protein), increased expression of GADD45a (growth arrest and DNA-damage-inducible protein) gene and inactivated Non homologous end joining (NHEJ) repair pathway. The comet formation in irradiated mice peripheral blood mononuclear cells (PBMC) reiterated the DNA damage in IR exposed groups. FA pretreatment significantly prevented the comet formation and regulated the nuclear translocation of p53, inhibited ATM activation and expression of GADD45a gene. FA promoted the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and activated NHEJ repair pathway to overcome ROS mediated oxidative stress and DNA damage. Therefore, the current study stated that FA can challenge the oxidative stress by (i) inducing nuclear translocation of Nrf2, (ii) scavenging ROS, and (iii) activating NHEJ DNA repair process.

The influence of TRP53 in the dose response of radiation-induced apoptosis, DNA repair and genomic stability in murine haematopoietic cells

DOE PAGES

Lemon, Jennifer A.; Taylor, Kristina; Verdecchia, Kyle; ...

2014-01-01

Apoptotic and DNA damage endpoints are frequently used as surrogate markers of cancer risk, and have been well-studied in the Trp53+/- mouse model. We report the effect of differing Trp53 gene status on the dose response of ionizing radiation exposures (0.01-2 Gy), with the unique perspective of determining if effects of gene status remain at extended time points. Here we report no difference in the dose response for radiation-induced DNA double-strand breaks in bone marrow and genomic instability (MN-RET levels) in peripheral blood, between wild-type ( Trp53+/+) and heterozygous ( Trp53+/-) mice. The dose response for Trp53+/+ mice showed highermore » initial levels of radiation-induced lymphocyte apoptosis relative to Trp53+/- between 0 and 1 Gy. Although this trend was observed up to 12 hours post-irradiation, both genotypes ultimately reached the same level of apoptosis at 14 hours, suggesting the importance of late-onset p53-independent apoptotic responses in this mouse model. Expected radiation-induced G1 cell cycle delay was observed in Trp53+/+ but not Trp53+/-. Although p53 has an important role in cancer risk, we have shown its influence on radiation dose response can be temporally variable. This research highlights the importance of caution when using haematopoietic endpoints as surrogates to extrapolate radiation-induced cancer risk estimation.« less

Lemon balm extract (Melissa officinalis, L.) promotes melanogenesis and prevents UVB-induced oxidative stress and DNA damage in a skin cell model.

PubMed

Pérez-Sánchez, Almudena; Barrajón-Catalán, Enrique; Herranz-López, María; Castillo, Julián; Micol, Vicente

2016-11-01

Solar ultraviolet (UV) radiation is one of the main causes of a variety of cutaneous disorders, including photoaging and skin cancer. Its UVB component (280-315nm) leads to oxidative stress and causes inflammation, DNA damage, p53 induction and lipid and protein oxidation. Recently, an increase in the use of plant polyphenols with antioxidant and anti-inflammatory properties has emerged to protect human skin against the deleterious effects of sunlight. This study evaluates the protective effects of lemon balm extract (LBE) (Melissa Officinalis, L) and its main phenolic compound rosmarinic acid (RA) against UVB-induced damage in human keratinocytes. The LBE composition was determined by HPLC analysis coupled to photodiode array detector and ion trap mass spectrometry with electrospray ionization (HPLC-DAD-ESI-IT-MS/MS). Cell survival, ROS generation and DNA damage were determined upon UVB irradiation in the presence of LBE. The melanogenic capacity of LBE was also determined. RA and salvianolic acid derivatives were the major compounds, but caffeic acid and luteolin glucuronide were also found in LBE. LBE and RA significantly increased the survival of human keratinocytes upon UVB radiation, but LBE showed a stronger effect. LBE significantly decreased UVB-induced intracellular ROS production. Moreover, LBE reduced UV-induced DNA damage and the DNA damage response (DDR), which were measured as DNA strand breaks in the comet assay and histone H2AX activation, respectively. Finally, LBE promoted melanogenesis in the cell model. These results suggest that LBE may be considered as a candidate for the development of oral/topical photoprotective ingredients against UVB-induced skin damage. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

DNA Dosimetry Assessment for Sunscreen Genotoxic Photoprotection

PubMed Central

Schuch, André Passaglia; Lago, Juliana Carvalhães; Yagura, Teiti; Menck, Carlos Frederico Martins

2012-01-01

Background Due to the increase of solar ultraviolet radiation (UV) incidence over the last few decades, the use of sunscreen has been widely adopted for skin protection. However, considering the high efficiency of sunlight-induced DNA lesions, it is critical to improve upon the current approaches that are used to evaluate protection factors. An alternative approach to evaluate the photoprotection provided by sunscreens against daily UV radiation-induced DNA damage is provided by the systematic use of a DNA dosimeter. Methodology/Principal Findings The Sun Protection Factor for DNA (DNA-SPF) is calculated by using specific DNA repair enzymes, and it is defined as the capacity for inhibiting the generation of cyclobutane pyrimidine dimers (CPD) and oxidised DNA bases compared with unprotected control samples. Five different commercial brands of sunscreen were initially evaluated, and further studies extended the analysis to include 17 other products representing various formulations and Sun Protection Factors (SPF). Overall, all of the commercial brands of SPF 30 sunscreens provided sufficient protection against simulated sunlight genotoxicity. In addition, this DNA biosensor was useful for rapidly screening the biological protection properties of the various sunscreen formulations. Conclusions/Significance The application of the DNA dosimeter is demonstrated as an alternative, complementary, and reliable method for the quantification of sunscreen photoprotection at the level of DNA damage. PMID:22768281

Evaluation of DNA damage induced by gamma radiation in gill and muscle tissues of Cyprinus carpio and their relative sensitivity.

PubMed

M K, Praveen Kumar; Shyama, Soorambail K; D'Costa, Avelyno; Kadam, Samit B; Sonaye, Bhagatsingh Harisingh; Chaubey, Ramesh Chandra

2017-10-01

The effect of radiation on the aquatic environment is of major concern in recent years. Limited data is available on the genotoxicity of gamma radiation on different tissues of aquatic organisms. Hence, the present investigation was carried out to study the DNA damage induced by gamma radiation in the gill and muscle tissues and their relative sensitivity using the comet assay in the freshwater teleost fish, common carp (Cyprinus carpio). The comet assay was optimized and validated in common carp using cyclophosphamide (CP), a reference genotoxic agent. The fish were exposed (acute) to various doses of gamma radiation (2, 4, 6, 8 and 10Gy) and samplings (gill and muscle tissue) were done at regular intervals (24, 48 and 72h) to assess the DNA damage. A significant increase in DNA damage was observed as indicated by an increase in % tail DNA for all doses of gamma radiation in both tissues. We also observed a dose-related increase and a time-dependent decrease of DNA damage. In comparison, DNA damage showed different sensitivity among the tissues at different doses. This shows that a particular dose may have different effects on different tissues which could be due to physiological factors of the particular tissue. Our study also suggests that the gills and muscle of fish are sensitive and reliable tissues for evaluating the genotoxic effects of reference and environmental agents, using the comet assay. Copyright © 2017. Published by Elsevier Inc.

Amplification of bovine papillomavirus DNA by N-methyl-N'-nitro-N-nitrosoguanidine, ultraviolet irradiation, or infection with herpes simplex virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmitt, J.; Schlehofer, J.R.; Mergener, K.

1989-09-01

Treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or irradiation with ultraviolet light (uv254 nm) induces amplification of integrated as well as episomal sequences of bovine papillomavirus (BPV) type 1 DNA in BPV-1-transformed mouse C127 cells (i.e., ID13 cells). This is shown by filter in situ hybridization and Southern blot analysis of cellular DNA. Similarly, infection of ID13 cells with herpes simplex virus (HSV) type 1 which has been shown to be mutagenic for host cell DNA leads to amplification of BPV DNA sequences. In contrast to this induction of DNA amplification by initiators, treatment of ID13 cells with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)more » does not result in increased synthesis of BPV DNA nor does TPA treatment modulate the initiator-induced DNA amplification. Similar to other cell systems infection with adeno-associated virus (AAV) type 2 inhibits BPV-1 DNA amplification irrespective of the inducing agent. In contrast to initiator-induced DNA amplification, treatment with carcinogen (MNNG) or tumor promoters or combination of MNNG and promoter of C127 cells prior to transformation by BPV-1 does not lead to an increase in the number of transformed foci. The induction of amplification of papillomavirus DNA by initiating agents possibly represents one of the mechanisms by which the observed synergism between papillomavirus infection and initiators in tumorigenesis might occur.« less

DNA Protection Protein, a Novel Mechanism of Radiation Tolerance: Lessons from Tardigrades

PubMed Central

Hashimoto, Takuma; Kunieda, Takekazu

2017-01-01

Genomic DNA stores all genetic information and is indispensable for maintenance of normal cellular activity and propagation. Radiation causes severe DNA lesions, including double-strand breaks, and leads to genome instability and even lethality. Regardless of the toxicity of radiation, some organisms exhibit extraordinary tolerance against radiation. These organisms are supposed to possess special mechanisms to mitigate radiation-induced DNA damages. Extensive study using radiotolerant bacteria suggested that effective protection of proteins and enhanced DNA repair system play important roles in tolerability against high-dose radiation. Recent studies using an extremotolerant animal, the tardigrade, provides new evidence that a tardigrade-unique DNA-associating protein, termed Dsup, suppresses the occurrence of DNA breaks by radiation in human-cultured cells. In this review, we provide a brief summary of the current knowledge on extremely radiotolerant animals, and present novel insights from the tardigrade research, which expand our understanding on molecular mechanism of exceptional radio-tolerability. PMID:28617314

DNA damage and repair after high LET radiation

NASA Astrophysics Data System (ADS)

O'Neill, Peter; Cucinotta, Francis; Anderson, Jennifer

Predictions from biophysical models of interactions of radiation tracks with cellular DNA indicate that clustered DNA damage sites, defined as two or more lesions formed within one or two helical turns of the DNA by passage of a single radiation track, are formed in mammalian cells. These complex DNA damage sites are regarded as a signature of ionizing radiation exposure particularly as the likelihood of clustered damage sites arising endogenously is low. For instance, it was predicted from biophysical modelling that 30-40% of low LET-induced double strand breaks (DSB), a form of clustered damage, are complex with the yield increasing to >90% for high LET radiation, consistent with the reduced reparability of DSB with increasing ionization density of the radiation. The question arises whether the increased biological effects such as mutagenesis, carcinogenesis and lethality is in part related to DNA damage complexity and/or spatial distribution of the damage sites, which may lead to small DNA fragments. With particle radiation it is also important to consider not only delta-rays which may cause clustered damaged sites and may be highly mutagenic but the non-random spatial distribution of DSB which may lead to deletions. In this overview I will concentrate on the molecular aspects of the variation of the complexity of DNA damage on radiation quality and the challenges this complexity presents the DNA damage repair pathways. I will draw on data from micro-irradiations which indicate that the repair of DSBs by non-homologous end joining is highly regulated with pathway choice and kinetics of repair dependent on the chemical complexity of the DSB. In summary the aim is to emphasis the link between the spatial distribution of energy deposition events related to the track, the molecular products formed and the consequence of damage complexity contributing to biological effects and to present some of the outstanding molecular challenges with particle radiation.

Molecular aspects of ultraviolet radiation-induced apoptosis in the skin.

PubMed

Chow, Jeffrey; Tron, Victor A

2005-12-01

Apoptosis, or programmed cell death, is an essential physiological process that controls cell numbers during physiological processes, and eliminates abnormal cells that can potentially harm an organism. This review summarizes our current state of knowledge of apoptosis induction in skin by UV radiation. A review of the literature was undertaken focusing on cell death in the skin secondary to UV radiation. It is evident that a number of apoptotic pathways, both intrinsic and extrinsic, are induced following exposure to damaging UV radiation. Although our understanding of the apoptotic processes is gradually increasing, many important aspects remain obscure. These include interconnections between pathways, wavelength-specific differences and cell type differences.

Low-dose environmental radiation, DNA damage, and cancer: the possible contribution of psychological factors.

PubMed

Cwikel, Julie G; Gidron, Yori; Quastel, Michael

2010-01-01

Radiation causes DNA damage, increases risk of cancer, and is associated with psychological stress responses. This article proposes an evidence-based integrative model in which psychological factors could interact with radiation by either augmenting or moderating the adverse effects of radiation on DNA integrity and eventual tumorigenesis. Based on a review of the literature, we demonstrate the following: (1) the effects of low-dose radiation exposures on DNA integrity and on tumorigenesis; (2) the effects of low-dose radiation exposure on psychological distress; (3) the relationship between psychological factors and DNA damage; and (4) the possibility that psychological stress augments and that psychological resource variables moderate radiation-induced DNA damage and risk of cancer. The additional contribution of psychological processes to radiation-DNA damage-cancer relationships needs further study, and if verified, has clinical implications.

Examining Dermatologist Use and Opinions of Ultraviolet Radiation for Cosmetic and Medical Purposes.

PubMed

Sampson, Blake P; Secrest, Aaron M; Hansen, Christopher B; Geller, Alan C

2018-02-01

BACKGROUND: The commercial tanning industry has opposed efforts to educate the public on the risks of tanning as well as attempts to restrict minors' access to tanning services. Despite a paucity of supporting literature, statements from the tanning industry claiming that dermatologists routinely use in-office phototherapy for cosmetic treatments and refer patients to tanning salons have successfully derailed and defeated legislation in many states. OBJECTIVE: This study aims to evaluate dermatologist referrals for ultraviolet radiation for cosmetic and medical purposes via tanning beds or phototherapy, as well as their opinions on tanning, legislation, and ultraviolet radiation counseling practices. DESIGN: The study was conducted using a 10-question anonymous survey. SETTING: The participants were surveyed during meetings of three regional dermatologic societies. PARTICIPANTS: One hundred and fifty-two dermatologists attending society meetings participated in the study. MEASURES: The authors measured physician referrals, opinions, and recommendations regarding ultraviolet exposure. RESULTS: Zero physicians (0/152) recommended tanning salons for cosmetic reasons. These 152 dermatologists referred 458 (417 adult, 41 pediatric) out of an estimated 809,369 patients (0.057%) to tanning salons for medical treatment. Of these physicians, 76 out of 152 and 15 out of 152 reported referring at least one adult or one pediatric patient, respectively, within the last year. All respondents supported ultraviolet tanning legislation and discouraged cosmetic tanning. CONCLUSION: These findings directly contradict the assertion that dermatologists use ultraviolet radiation for cosmetic purposes or routinely refer patients to tanning salons. This study underscores the complex nature of ultraviolet radiation, as dermatologists infrequently utilize ultraviolet radiation for medical purposes and unanimously support restrictive legislation. In addition, these dermatologists counsel

Examining Dermatologist Use and Opinions of Ultraviolet Radiation for Cosmetic and Medical Purposes

PubMed Central

Secrest, Aaron M.; Hansen, Christopher B.; Geller, Alan C.

2018-01-01

BACKGROUND: The commercial tanning industry has opposed efforts to educate the public on the risks of tanning as well as attempts to restrict minors’ access to tanning services. Despite a paucity of supporting literature, statements from the tanning industry claiming that dermatologists routinely use in-office phototherapy for cosmetic treatments and refer patients to tanning salons have successfully derailed and defeated legislation in many states. OBJECTIVE: This study aims to evaluate dermatologist referrals for ultraviolet radiation for cosmetic and medical purposes via tanning beds or phototherapy, as well as their opinions on tanning, legislation, and ultraviolet radiation counseling practices. DESIGN: The study was conducted using a 10-question anonymous survey. SETTING: The participants were surveyed during meetings of three regional dermatologic societies. PARTICIPANTS: One hundred and fifty-two dermatologists attending society meetings participated in the study. MEASURES: The authors measured physician referrals, opinions, and recommendations regarding ultraviolet exposure. RESULTS: Zero physicians (0/152) recommended tanning salons for cosmetic reasons. These 152 dermatologists referred 458 (417 adult, 41 pediatric) out of an estimated 809,369 patients (0.057%) to tanning salons for medical treatment. Of these physicians, 76 out of 152 and 15 out of 152 reported referring at least one adult or one pediatric patient, respectively, within the last year. All respondents supported ultraviolet tanning legislation and discouraged cosmetic tanning. CONCLUSION: These findings directly contradict the assertion that dermatologists use ultraviolet radiation for cosmetic purposes or routinely refer patients to tanning salons. This study underscores the complex nature of ultraviolet radiation, as dermatologists infrequently utilize ultraviolet radiation for medical purposes and unanimously support restrictive legislation. In addition, these dermatologists counsel

Radiation-damage-induced phasing: a case study using UV irradiation with light-emitting diodes.

PubMed

de Sanctis, Daniele; Zubieta, Chloe; Felisaz, Franck; Caserotto, Hugo; Nanao, Max H

2016-03-01

Exposure to X-rays, high-intensity visible light or ultraviolet radiation results in alterations to protein structure such as the breakage of disulfide bonds, the loss of electron density at electron-rich centres and the movement of side chains. These specific changes can be exploited in order to obtain phase information. Here, a case study using insulin to illustrate each step of the radiation-damage-induced phasing (RIP) method is presented. Unlike a traditional X-ray-induced damage step, specific damage is introduced via ultraviolet light-emitting diodes (UV-LEDs). In contrast to UV lasers, UV-LEDs have the advantages of small size, low cost and relative ease of use.

Epigenetic Analysis of Heavy-ion Radiation Induced Bystander Effects in Mice

NASA Astrophysics Data System (ADS)

Zhang, Meng; Sun, Yeqing; Cui, Changna; Xue, Bei

Abstract: Radiation-induced bystander effect was defined as the induction of damage in neighboring non-hit cells by signals released from directly-irradiated cells. Recently, low dose of high LET radiation induced bystander effects in vivo have been reported more and more. It has been indicated that radiation induced bystander effect was localized not only in bystander tissues but also in distant organs. Genomic, epigenetic and proteomics plays significant roles in regulating heavy-ion radiation stress responses in mice. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male Balb/c and C57BL mice were exposed head-only to 40, 200, 2000mGy dose of (12) C heavy-ion radiation, while the rest of the animal body was shielded. Directly radiation organ ear and the distant organ liver were detected on 1h, 6h, 12h and 24h after radiation, respectively. Methylation-sensitive amplification polymorphism (MSAP) was used to monitor the level of polymorphic genomic DNA methylation changed with dose and time effects. The results show that heavy-ion irradiated mouse head could induce genomic DNA methylation changes significantly in both the directly radiation organ ear and the distant organ liver. The percent of DNA methylation changes were time-dependent and tissue-specific. Demethylation polymorphism rate was highest separately at 1 h in 200 mGy and 6 h in 2000 mGy after irradiation. The global DNA methylation changes tended to occur in the CG sites. The results illustrated that genomic methylation changes of heavy ion radiation-induced bystander effect in liver could be obvious 1 h after radiation and achieved the maximum at 6 h, while the changes could recover gradually at 12 h. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in both directly radiation organ ear and distant organ liver. Moreover, our findings are important to understand the molecular mechanism of

Crosstalk between telomere maintenance and radiation effects: A key player in the process of radiation-induced carcinogenesis

PubMed Central

Shim, Grace; Ricoul, Michelle; Hempel, William M.; Azzam, Edouard I.; Sabatier, Laure

2014-01-01

It is well established that ionizing radiation induces chromosomal damage, both following direct radiation exposure and via non-targeted (bystander) effects, activating DNA damage repair pathways, of which the proteins are closely linked to telomeric proteins and telomere maintenance. Long-term propagation of this radiation-induced chromosomal damage during cell proliferation results in chromosomal instability. Many studies have shown the link between radiation exposure and radiation-induced changes in oxidative stress and DNA damage repair in both targeted and non-targeted cells. However, the effect of these factors on telomeres, long established as guardians of the genome, still remains to be clarified. In this review, we will focus on what is known about how telomeres are affected by exposure to low- and high-LET ionizing radiation and during proliferation, and will discuss how telomeres may be a key player in the process of radiation-induced carcinogenesis. PMID:24486376

DNA Damage Signals and Space Radiation Risk

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.

2011-01-01

Space radiation is comprised of high-energy and charge (HZE) nuclei and protons. The initial DNA damage from HZE nuclei is qualitatively different from X-rays or gamma rays due to the clustering of damage sites which increases their complexity. Clustering of DNA damage occurs on several scales. First there is clustering of single strand breaks (SSB), double strand breaks (DSB), and base damage within a few to several hundred base pairs (bp). A second form of damage clustering occurs on the scale of a few kbp where several DSB?s may be induced by single HZE nuclei. These forms of damage clusters do not occur at low to moderate doses of X-rays or gamma rays thus presenting new challenges to DNA repair systems. We review current knowledge of differences that occur in DNA repair pathways for different types of radiation and possible relationships to mutations, chromosomal aberrations and cancer risks.

Radiative lifetimes in B I using ultraviolet and vacuum-ultraviolet laser-induced fluorescence

NASA Technical Reports Server (NTRS)

O'Brian, T. R.; Lawler, J. E.

1992-01-01

Radiative lifetimes of the eight lowest even parity levels in the doublet system of B I are measured using time-resolved laser-induced fluorescence in the UV and VUV on an atomic beam of boron. The accurate lifetimes provide a base for improved determination of absolute transition probabilities in B I. The techniques described are broadly applicable to measurement of lifetimes of levels with transitions in the visible, UV, and VUV in almost any element.

Some Thoughts on Teaching about Ultraviolet Radiation

ERIC Educational Resources Information Center

Thumm, Walter

1975-01-01

Describes the major obstacles in the study of ultraviolet radiation (UV). Presents the beneficial aspects of UV such as vitamin O production, sterilization, clinical treatment of diseases and wounds, and the marking of patients for radiotherapy. Warns of the dangers of UV exposure such as skin cancer and early aging. (GS)

Repair of DNA damage induced by accelerated heavy ions--a mini review.

PubMed

Okayasu, Ryuichi

2012-03-01

Increasing use of heavy ions for cancer therapy and concerns from exposure to heavy charged particles in space necessitate the study of the basic biological mechanisms associated with exposure to heavy ions. As the most critical damage induced by ionizing radiation is DNA double strand break (DSB), this review focuses on DSBs induced by heavy ions and their repair processes. Compared with X- or gamma-rays, high-linear energy transfer (LET) heavy ion radiation induces more complex DNA damage, categorized into DSBs and non-DSB oxidative clustered DNA lesions (OCDL). This complexity makes the DNA repair process more difficult, partially due to retarded enzymatic activities, leading to increased chromosome aberrations and cell death. In general, the repair process following heavy ion exposure is LET-dependent, but with nonhomologous end joining defective cells, this trend is less emphasized. The variation in cell survival levels throughout the cell cycle is less prominent in cells exposed to high-LET heavy ions when compared with low LET, but this mechanism has not been well understood until recently. Involvement of several DSB repair proteins is suggested to underlie this interesting phenomenon. Recent improvements in radiation-induced foci studies combined with high-LET heavy ion exposure could provide a useful opportunity for more in depth study of DSB repair processes. Accelerated heavy ions have become valuable tools to investigate the molecular mechanisms underlying repair of DNA DSBs, the most crucial form of DNA damage induced by radiation and various chemotherapeutic agents. Copyright © 2011 UICC.

Spectrum of complex DNA damages depends on the incident radiation

NASA Astrophysics Data System (ADS)

Hada, M.; Sutherland, B.

Ionizing radiation induces clustered DNA damages in DNA-two or more abasic sites oxidized bases and strand breaks on opposite DNA strands within a few helical turns Clustered damages are considered to be difficult to repair and therefore potentially lethal and mutagenic damages Although induction of single strand breaks and isolated lesions has been studied extensively little is known of factors affecting induction of clusters other than double strand breaks DSB The aim of the present study was to determine whether the type of incident radiation could affect yield or spectra of specific clusters Genomic T7 DNA a simple 40 kbp linear blunt-ended molecule was irradiated in non-scavenging buffer conditions with Fe 970 MeV n Ti 980 MeV n C 293 MeV n Si 586 MeV n ions or protons 1 GeV n at the NASA Space Radiation Laboratory or with 100 kVp X-rays Irradiated DNA was treated with homogeneous Fpg or Nfo proteins or without enzyme treatment for DSB quantitation then electrophoresed in neutral agarose gels DSB Fpg-OxyPurine clusters and Nfo-Abasic clusters were quantified by number average length analysis The results show that the yields of all these complex damages depend on the incident radiation Although LETs are similar protons induced twice as many DSBs than did X-rays Further the spectrum of damage also depends on the radiation The yield damage Mbp Gy of all damages decreased with increasing linear energy transfer LET of the radiation The relative frequencies of DSBs to Abasic- and OxyBase clusters were higher

REC-2006-A Fractionated Extract of Podophyllum hexandrum Protects Cellular DNA from Radiation-Induced Damage by Reducing the Initial Damage and Enhancing Its Repair In Vivo.

PubMed

Chaudhary, Pankaj; Shukla, Sandeep Kumar; Sharma, Rakesh Kumar

2011-01-01

Podophyllum hexandrum, a perennial herb commonly known as the Himalayan May Apple, is well known in Indian and Chinese traditional systems of medicine. P. hexandrum has been widely used for the treatment of venereal warts, skin infections, bacterial and viral infections, and different cancers of the brain, lung and bladder. This study aimed at elucidating the effect of REC-2006, a bioactive fractionated extract from the rhizome of P. hexandrum, on the kinetics of induction and repair of radiation-induced DNA damage in murine thymocytes in vivo. We evaluated its effect on non-specific radiation-induced DNA damage by the alkaline halo assay in terms of relative nuclear spreading factor (RNSF) and gene-specific radiation-induced DNA damage via semi-quantitative polymerase chain reaction. Whole body exposure of animals with gamma rays (10 Gy) caused a significant amount of DNA damage in thymocytes (RNSF values 17.7 ± 0.47, 12.96 ± 1.64 and 3.3 ± 0.014) and a reduction in the amplification of β-globin gene to 0, 28 and 43% at 0, 15 and 60 min, respectively. Administrating REC-2006 at a radioprotective concentration (15 mg kg(-1) body weight) 1 h before irradiation resulted in time-dependent reduction of DNA damage evident as a decrease in RNSF values 6.156 ± 0.576, 1.647 ± 0.534 and 0.496 ± 0.012, and an increase in β-globin gene amplification 36, 95 and 99%, at 0, 15 and 60 min, respectively. REC-2006 scavenged radiation-induced hydroxyl radicals in a dose-dependent manner stabilized DPPH free radicals and also inhibited superoxide anions. Various polyphenols and flavonoides present in REC-2006 might contribute to scavenging of radiation-induced free radicals, thereby preventing DNA damage and stimulating its repair.

Sequence dependence of electron-induced DNA strand breakage revealed by DNA nanoarrays

PubMed Central

Keller, Adrian; Rackwitz, Jenny; Cauët, Emilie; Liévin, Jacques; Körzdörfer, Thomas; Rotaru, Alexandru; Gothelf, Kurt V.; Besenbacher, Flemming; Bald, Ilko

2014-01-01

The electronic structure of DNA is determined by its nucleotide sequence, which is for instance exploited in molecular electronics. Here we demonstrate that also the DNA strand breakage induced by low-energy electrons (18 eV) depends on the nucleotide sequence. To determine the absolute cross sections for electron induced single strand breaks in specific 13 mer oligonucleotides we used atomic force microscopy analysis of DNA origami based DNA nanoarrays. We investigated the DNA sequences 5′-TT(XYX)3TT with X = A, G, C and Y = T, BrU 5-bromouracil and found absolute strand break cross sections between 2.66 · 10−14 cm2 and 7.06 · 10−14 cm2. The highest cross section was found for 5′-TT(ATA)3TT and 5′-TT(ABrUA)3TT, respectively. BrU is a radiosensitizer, which was discussed to be used in cancer radiation therapy. The replacement of T by BrU into the investigated DNA sequences leads to a slight increase of the absolute strand break cross sections resulting in sequence-dependent enhancement factors between 1.14 and 1.66. Nevertheless, the variation of strand break cross sections due to the specific nucleotide sequence is considerably higher. Thus, the present results suggest the development of targeted radiosensitizers for cancer radiation therapy. PMID:25487346

Ultraviolet Radiation Dose National Standard of México

NASA Astrophysics Data System (ADS)

Cardoso, R.; Rosas, E.

2006-09-01

We present the Ultraviolet (UV) Radiation Dose National Standard for México. The establishment of this measurement reference at Centro Nacional de Metrología (CENAM) eliminates the need of contacting foreign suppliers in the search for traceability towards the SI units when calibrating instruments at 365 nm. Further more, the UV Radiation Dose National Standard constitutes a highly accurate and reliable source for the UV radiation dose measurements performed in medical and cosmetic treatments as in the the food and pharmaceutics disinfection processes, among other.

Ultraviolet Radiation: Human Exposure and Health Risks.

ERIC Educational Resources Information Center

Tenkate, Thomas D.

1998-01-01

Provides an overview of human exposure to ultraviolet radiation and associated health effects as well as risk estimates for acute and chronic conditions resulting from such exposure. Demonstrates substantial reductions in health risk that can be achieved through preventive actions. Also includes a risk assessment model for skin cancer. Contains 36…

Moderate salt treatment alleviates ultraviolet-B radiation caused impairment in poplar plants

NASA Astrophysics Data System (ADS)

Ma, Xuan; Ou, Yong-Bin; Gao, Yong-Feng; Lutts, Stanley; Li, Tao-Tao; Wang, Yang; Chen, Yong-Fu; Sun, Yu-Fang; Yao, Yin-An

2016-09-01

The effects of moderate salinity on the responses of woody plants to UV-B radiation were investigated using two Populus species (Populus alba and Populus russkii). Under UV-B radiation, moderate salinity reduced the oxidation pressure in both species, as indicated by lower levels of cellular H2O2 and membrane peroxidation, and weakened the inhibition of photochemical efficiency expressed by O-J-I-P changes. UV-B-induced DNA lesions in chloroplast and nucleus were alleviated by salinity, which could be explained by the higher expression levels of DNA repair system genes under UV-B&salt condition, such as the PHR, DDB2, and MutSα genes. The salt-induced increase in organic osmolytes proline and glycine betaine, afforded more efficient protection against UV-B radiation. Therefore moderate salinity induced cross-tolerance to UV-B stress in poplar plants. It is thus suggested that woody plants growing in moderate salted condition would be less affected by enhanced UV-B radiation than plants growing in the absence of salt. Our results also showed that UV-B signal genes in poplar plants PaCOP1, PaSTO and PaSTH2 were quickly responding to UV-B radiation, but not to salt. The transcripts of PaHY5 and its downstream pathway genes (PaCHS1, PaCHS4, PaFLS1 and PaFLS2) were differently up-regulated by these treatments, but the flavonoid compounds were not involved in the cross-tolerance since their concentration increased to the same extent in both UV-B and combined stresses.

ASSESSMENT OF THE RISK OF SOLAR ULTRAVIOLET RADIATION TO AMPHIBIANS. II: IN SITU CHARACTERIZATION OF SOLAR ULTRAVIOLET RADIATION IN AMPHIBIAN HABITATS

EPA Science Inventory

Ultraviolet B (UVB) radiation has been hypothesized as a potential cause of amphibian population declines and increased incidences of malformations. Realistic studies documenting UV irradiance or dose have rarely been conducted in wetlands used by amphibians. We demonstrate that ...

Electromagnetic noise inhibits radiofrequency radiation-induced DNA damage and reactive oxygen species increase in human lens epithelial cells.

PubMed

Yao, Ke; Wu, Wei; Wang, KaiJun; Ni, Shuang; Ye, PanPan; Yu, YiBo; Ye, Juan; Sun, LiXia

2008-05-19

The goal of this study was to investigate whether superposing of electromagnetic noise could block or attenuate DNA damage and intracellular reactive oxygen species (ROS) increase of cultured human lens epithelial cells (HLECs) induced by acute exposure to 1.8 GHz radiofrequency field (RF) of the Global System for Mobile Communications (GSM). An sXc-1800 RF exposure system was used to produce a GSM signal at 1.8 GHz (217 Hz amplitude-modulated) with the specific absorption rate (SAR) of 1, 2, 3, and 4 W/kg. After 2 h of intermittent exposure, the ROS level was assessed by the fluorescent probe, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). DNA damage to HLECs was examined by alkaline comet assay and the phosphorylated form of histone variant H2AX (gammaH2AX) foci formation assay. After exposure to 1.8 GHz RF for 2 h, HLECs exhibited significant intracellular ROS increase in the 2, 3, and 4 W/kg groups. RF radiation at the SAR of 3 W/kg and 4 W/kg could induce significant DNA damage, examined by alkaline comet assay, which was used to detect mainly single strand breaks (SSBs), while no statistical difference in double strand breaks (DSBs), evaluated by gammaH2AX foci, was found between RF exposure (SAR: 3 and 4 W/kg) and sham exposure groups. When RF was superposed with 2 muT electromagnetic noise could block RF-induced ROS increase and DNA damage. DNA damage induced by 1.8 GHz radiofrequency field for 2 h, which was mainly SSBs, may be associated with the increased ROS production. Electromagnetic noise could block RF-induced ROS formation and DNA damage.

Silymarin inhibits ultraviolet radiation-induced immune suppression through DNA repair-dependent activation of dendritic cells and stimulation of effector T cells

PubMed Central

Vaid, Mudit; Prasad, Ram; Singh, Tripti; Elmets, Craig A.; Xu, Hui; Katiyar, Santosh K.

2013-01-01

Silymarin inhibits UVB-induced immunosuppression in mouse skin. To identify the molecular mechanisms underlying this effect, we used an adoptive transfer approach in which dendritic cells (DCs) from the draining lymph nodes of donor mice that had been UVB-exposed and sensitized to 2,4,-dinitrofluorobenzene (DNFB) were transferred into naïve recipient mice. The contact hypersensitivity (CHS) response of the recipient mice to DNFB was then measured. When DCs were obtained from UVB-exposed donor mice that were not treated with silymarin, the CHS response was suppressed confirming the role of DCs in the UVB-induced immunosuppression. Silymarin treatment of UVB-exposed donor mice relieved this suppression of the CHS response in the recipients. Silymarin treatment was associated with rapid repair of UVB-induced cyclobutane pyrimidine dimers (CPDs) in DCs and silymarin treatment did not prevent UV-induced immunosuppression in XPA-deficient mice which are unable to repair UV-induced DNA damage. The CHS response in mice receiving DCs from silymarin-treated UV-exposed donor mice also was associated with enhanced secretion of Th1-type cytokines and stimulation of T cells. Adoptive transfer of T cells revealed that transfer of either CD8+ or CD4+ cells from silymarin-treated, UVB-exposed donors resulted in enhancement of the CHS response. Cell culture study showed enhanced secretion of IL-2 and IFNγ by CD8+ T cells, and reduced secretion of Th2 cytokines by CD4+ cells, obtained from silymarin-treated UVB-exposed mice. These data suggest that DNA repair-dependent functional activation of DCs, a reduction in CD4+ regulatory T-cell activity, and stimulation of CD8+ effector T cells contribute to silymarin-mediated inhibition of UVB-induced immunosuppression. PMID:23395695

Oxidative stress-induced protein damage inhibits DNA repair and determines mutation risk and anticancer drug effectiveness

PubMed Central

McAdam, Elizabeth; Brem, Reto; Karran, Peter

2016-01-01

The relationship between sun exposure and non-melanoma skin cancer risk is well established. Solar ultraviolet radiation (UV; wavelengths 280-400 nm) is firmly implicated in skin cancer development. Nucleotide excision repair (NER) protects against cancer by removing potentially mutagenic DNA lesions induced by UVB (280-320 nm). How the 20-fold more abundant UVA (320-400 mn) component of solar UV radiation increases skin cancer risk is not understood. We demonstrate here that the contribution of UVA to the effects of UV radiation on cultured human cells is largely independent of its ability to damage DNA. Instead, the effects of UVA reflect the induction of oxidative stress that causes extensive protein oxidation. Because NER proteins are among those damaged, UVA irradiation inhibits NER and increases the cells’ susceptibility to mutation by UVB. NER inhibition is a common consequence of oxidative stress. Exposure to chemical oxidants, treatment with drugs that deplete cellular antioxidants, and interventions that interfere with glucose metabolism to disrupt the supply of cellular reducing power all inhibit NER. Tumor cells are often in a condition of oxidative stress and one effect of the NER inhibition that results from stress-induced protein oxidation is an increased sensitivity to the anticancer drug cisplatin. Statement of implication: Since NER is both a defence against cancer a significant determinant of cell survival after treatment with anticancer drugs, its attenuation by protein damage under conditions of oxidative-stress has implications for both cancer risk and for the effectiveness of anticancer therapy. PMID:27106867

Ultraviolet B radiation induces impaired lifecycle traits and modulates expression of cytochrome P450 (CYP) genes in the copepod Tigriopus japonicus.

PubMed

Puthumana, Jayesh; Lee, Min-Chul; Park, Jun Chul; Kim, Hui-Su; Hwang, Dae-Sik; Han, Jeonghoon; Lee, Jae-Seong

2017-03-01

To evaluate the effects of ultraviolet B (UV-B) radiation at the developmental, reproductive, and molecular levels in aquatic invertebrates, we measured UV-B-induced acute toxicity, impairments in developmental and reproductive traits, and UV-B interaction with the entire family of cytochrome P450 (CYP) genes in the intertidal benthic copepod Tigriopus japonicus. We found a significant, dose-dependent reduction (P<0.05) in the survival of T. japonicus that began as a developmental delay and decreased fecundity. The 48h LD10 and LD50 were 1.35 and 1.84kJ/m 2 , and the CYP inhibitor (PBO) elevated mortality, confirming the involvement of CYP genes in UV-B induced toxicity. Low-dose UV-B (1.5kJ/m 2 ) induced developmental delays, and higher doses (6-18kJ/m 2 ) caused reproductive impairments in ovigerous females. The significant up-regulation of CYP genes belonging to clans 2/3/MT/4/20 in T. japonicus exposed to UV-B (12kJ/m 2 ) confirmed molecular interaction between UV-B and CYP genes. Moreover, orphan CYPs, such as CYP20A1, provide good insight on the deorphanization of invertebrate CYPs. Overall, these results demonstrate the involvement of UV-B radiation in the expression of all the CYP genes in T. japonicus and their susceptibility to UV-B radiation. This will provide a better understanding of the mechanistic effects of UV-B in copepods through the predicted AhR-mediated up-regulation of CYP genes. Copyright © 2017 Elsevier B.V. All rights reserved.

Key issues of ultraviolet radiation of OH at high altitudes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yuhuai; Wan, Tian; Jiang, Jianzheng

2014-12-09

Ultraviolet (UV) emissions radiated by hydroxyl (OH) is one of the fundamental elements in the prediction of radiation signature of high-altitude and high-speed vehicle. In this work, the OH A{sup 2}Σ{sup +}→X{sup 2}Π ultraviolet emission band behind the bow shock is computed under the experimental condition of the second bow-shock ultraviolet flight (BSUV-2). Four related key issues are discussed, namely, the source of hydrogen element in the high-altitude atmosphere, the formation mechanism of OH species, efficient computational algorithm of trace species in rarefied flows, and accurate calculation of OH emission spectra. Firstly, by analyzing the typical atmospheric model, the verticalmore » distributions of the number densities of different species containing hydrogen element are given. According to the different dominating species containing hydrogen element, the atmosphere is divided into three zones, and the formation mechanism of OH species is analyzed in the different zones. The direct simulation Monte Carlo (DSMC) method and the Navier-Stokes equations are employed to compute the number densities of the different OH electronically and vibrationally excited states. Different to the previous work, the trace species separation (TSS) algorithm is applied twice in order to accurately calculate the densities of OH species and its excited states. Using a non-equilibrium radiation model, the OH ultraviolet emission spectra and intensity at different altitudes are computed, and good agreement is obtained with the flight measured data.« less

Key issues of ultraviolet radiation of OH at high altitudes

NASA Astrophysics Data System (ADS)

Zhang, Yuhuai; Wan, Tian; Jiang, Jianzheng; Fan, Jing

2014-12-01

Ultraviolet (UV) emissions radiated by hydroxyl (OH) is one of the fundamental elements in the prediction of radiation signature of high-altitude and high-speed vehicle. In this work, the OH A2Σ+→ X2Π ultraviolet emission band behind the bow shock is computed under the experimental condition of the second bow-shock ultraviolet flight (BSUV-2). Four related key issues are discussed, namely, the source of hydrogen element in the high-altitude atmosphere, the formation mechanism of OH species, efficient computational algorithm of trace species in rarefied flows, and accurate calculation of OH emission spectra. Firstly, by analyzing the typical atmospheric model, the vertical distributions of the number densities of different species containing hydrogen element are given. According to the different dominating species containing hydrogen element, the atmosphere is divided into three zones, and the formation mechanism of OH species is analyzed in the different zones. The direct simulation Monte Carlo (DSMC) method and the Navier-Stokes equations are employed to compute the number densities of the different OH electronically and vibrationally excited states. Different to the previous work, the trace species separation (TSS) algorithm is applied twice in order to accurately calculate the densities of OH species and its excited states. Using a non-equilibrium radiation model, the OH ultraviolet emission spectra and intensity at different altitudes are computed, and good agreement is obtained with the flight measured data.

Use of near infrared femtosecond lasers as sub-micron radiation microbeam for cell DNA damage and repair studies.

PubMed

Botchway, S W; Reynolds, P; Parker, A W; O'Neill, P

2010-01-01

Laser induced radiation microbeam technology for radiobiology research is undergoing rapid growth because of the increased availability and ease of use of femtosecond laser sources. The main processes involved are multiphoton absorption and/or plasma formation. The high peak powers these lasers generate make them ideal tools for depositing sub-micrometer size radiant energy within a region of a living cell nucleus to activate ionising and/or photochemically driven processes. The technique allows questions relating to the effects of low doses of radiation, the propagation and treatment of deoxyribonucleic acid (DNA) damage and repair in individual live cells as well as non-targeted cell to cell effects to be addressed. This mini-review focuses on the use of near infrared (NIR) ca. 800nm radiation to induce damage that is radically different from the early and subsequent ultraviolet microbeam techniques. Ultrafast pulsed NIR instrumentation has many benefits including the ability to eliminate issues of unspecific UV absorption by the many materials prevalent within cells. The multiphoton interaction volume also permits energy deposition beyond the diffraction limit. Work has established that the fundamental process of the damage induced by the ultrashort laser pulses is different to those induced from continuous wave light sources. Pioneering work has demonstrated that NIR laser microbeam radiation can mimic ionising radiation via multiphoton absorption within the 3D femtolitre volume of the highly focused Gaussian beam. This light-matter interaction phenomenon provides a novel optical microbeam probe for mimicking both complex ionising and UV radiation-type cell damage including double strand breaks (DSBs) and base damage. A further advantage of the pulsed laser technique is that it provides further scope for time-resolved experiments. Recently the NIR laser microbeam technique has been used to investigate the recruitment of repair proteins to the sub

Photosynthetically active radiation (PAR) x ultraviolet radiation (UV) interact to initiate solar injury in apple

USDA-ARS?s Scientific Manuscript database

Sunburn or solar injury (SI) in apple is associated with high temperature, high visible light and ultraviolet radiation (UV). Fruit surface temperature (FST) thresholds for SI related disorders have been developed but there are no thresholds established for solar radiation. The objectives of the s...

REC-2006—A Fractionated Extract of Podophyllum hexandrum Protects Cellular DNA from Radiation-Induced Damage by Reducing the Initial Damage and Enhancing Its Repair In Vivo

PubMed Central

Chaudhary, Pankaj; Shukla, Sandeep Kumar; Sharma, Rakesh Kumar

2011-01-01

Podophyllum hexandrum, a perennial herb commonly known as the Himalayan May Apple, is well known in Indian and Chinese traditional systems of medicine. P. hexandrum has been widely used for the treatment of venereal warts, skin infections, bacterial and viral infections, and different cancers of the brain, lung and bladder. This study aimed at elucidating the effect of REC-2006, a bioactive fractionated extract from the rhizome of P. hexandrum, on the kinetics of induction and repair of radiation-induced DNA damage in murine thymocytes in vivo. We evaluated its effect on non-specific radiation-induced DNA damage by the alkaline halo assay in terms of relative nuclear spreading factor (RNSF) and gene-specific radiation-induced DNA damage via semi-quantitative polymerase chain reaction. Whole body exposure of animals with gamma rays (10 Gy) caused a significant amount of DNA damage in thymocytes (RNSF values 17.7 ± 0.47, 12.96 ± 1.64 and 3.3 ± 0.014) and a reduction in the amplification of β-globin gene to 0, 28 and 43% at 0, 15 and 60 min, respectively. Administrating REC-2006 at a radioprotective concentration (15 mg kg−1 body weight) 1 h before irradiation resulted in time-dependent reduction of DNA damage evident as a decrease in RNSF values 6.156 ± 0.576, 1.647 ± 0.534 and 0.496 ± 0.012, and an increase in β-globin gene amplification 36, 95 and 99%, at 0, 15 and 60 min, respectively. REC-2006 scavenged radiation-induced hydroxyl radicals in a dose-dependent manner stabilized DPPH free radicals and also inhibited superoxide anions. Various polyphenols and flavonoides present in REC-2006 might contribute to scavenging of radiation-induced free radicals, thereby preventing DNA damage and stimulating its repair. PMID:20008078

Divergence in DNA photorepair efficiency among genotypes from contrasting UV radiation environments in nature.

PubMed

Miner, Brooks E; Kulling, Paige M; Beer, Karlyn D; Kerr, Benjamin

2015-12-01

Populations of organisms routinely face abiotic selection pressures, and a central goal of evolutionary biology is to understand the mechanistic underpinnings of adaptive phenotypes. Ultraviolet radiation (UVR) is one of earth's most pervasive environmental stressors, potentially damaging DNA in any organism exposed to solar radiation. We explored mechanisms underlying differential survival following UVR exposure in genotypes of the water flea Daphnia melanica derived from natural ponds of differing UVR intensity. The UVR tolerance of a D. melanica genotype from a high-UVR habitat depended on the presence of visible and UV-A light wavelengths necessary for photoenzymatic repair of DNA damage, a repair pathway widely shared across the tree of life. We then measured the acquisition and repair of cyclobutane pyrimidine dimers, the primary form of UVR-caused DNA damage, in D. melanica DNA following experimental UVR exposure. We demonstrate that genotypes from high-UVR habitats repair DNA damage faster than genotypes from low-UVR habitats in the presence of visible and UV-A radiation necessary for photoenzymatic repair, but not in dark treatments. Because differences in repair rate only occurred in the presence of visible and UV-A radiation, we conclude that differing rates of DNA repair, and therefore differential UVR tolerance, are a consequence of variation in photoenzymatic repair efficiency. We then rule out a simple gene expression hypothesis for the molecular basis of differing repair efficiency, as expression of the CPD photolyase gene photorepair did not differ among D. melanica lineages, in both the presence and absence of UVR. © 2015 John Wiley & Sons Ltd.

Protective effect of curcumin against ultraviolet A irradiation‑induced photoaging in human dermal fibroblasts.

PubMed

Liu, Xiaoming; Zhang, Ruizhi; Shi, Haixia; Li, Xiaobo; Li, Yanhong; Taha, Ahmad; Xu, Chunxing

2018-05-01

Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in skin, resulting in photoaging. Natural botanicals have gained considerable attention due to their beneficial protection against the harmful effects of UV irradiation. The present study aimed to evaluate the ability of curcumin (Cur) to protect human dermal fibroblasts (HDFs) against ultraviolet A (UVA)‑induced photoaging. HDFs were treated with 0‑10 µM Cur for 2 h and subsequently exposed to various intensities of UVA irradiation. The cell viability and apoptotic rate of HDFs were investigated by MTT and flow cytometry assays, respectively. The effect of UVA and Cur on the formation of reactive oxygen species (ROS), malondialdehyde levels, which are an indicator of ROS, and the levels/activity of antioxidative defense proteins, including glutathione, superoxide dismutase and catalase, were evaluated using 2',7'-dichlorofluorescin diacetate and commercial assay kits. Furthermore, western blotting was performed to determine the levels of proteins associated with endoplasmic reticulum (ER) stress, the apoptotic pathway, inflammation and the collagen synthesis pathway. The results demonstrated that Cur reduced the accumulation of ROS and restored the activity of antioxidant defense enzymes, indicating that Cur minimized the damage induced by UVA irradiation in HDFs. Furthermore, western blot analysis demonstrated that Cur may attenuate UVA‑induced ER stress, inflammation and apoptotic signaling by downregulating the protein expression of glucose‑regulated protein 78, C/EBP‑homologous protein, nuclear factor‑κB and cleaved caspase‑3, while upregulating the expression of Bcl‑2. Additionally, it was demonstrated that Cur may regulate collagen metabolism by decreasing the protein expression of matrix metalloproteinase (MMP)‑1 and MMP‑3, and may promote the repair of cells damaged as a result of UVA irradiation through increasing the protein expression of

Protective effect of curcumin against ultraviolet A irradiation-induced photoaging in human dermal fibroblasts

PubMed Central

Liu, Xiaoming; Zhang, Ruizhi; Shi, Haixia; Li, Xiaobo; Li, Yanhong; Taha, Ahmad; Xu, Chunxing

2018-01-01

Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in skin, resulting in photoaging. Natural botanicals have gained considerable attention due to their beneficial protection against the harmful effects of UV irradiation. The present study aimed to evaluate the ability of curcumin (Cur) to protect human dermal fibroblasts (HDFs) against ultraviolet A (UVA)-induced photoaging. HDFs were treated with 0–10 µM Cur for 2 h and subsequently exposed to various intensities of UVA irradiation. The cell viability and apoptotic rate of HDFs were investigated by MTT and flow cytometry assays, respectively. The effect of UVA and Cur on the formation of reactive oxygen species (ROS), malondialdehyde levels, which are an indicator of ROS, and the levels/activity of antioxidative defense proteins, including glutathione, superoxide dismutase and catalase, were evaluated using 2′,7′-dichlorofluorescin diacetate and commercial assay kits. Furthermore, western blotting was performed to determine the levels of proteins associated with endoplasmic reticulum (ER) stress, the apoptotic pathway, inflammation and the collagen synthesis pathway. The results demonstrated that Cur reduced the accumulation of ROS and restored the activity of antioxidant defense enzymes, indicating that Cur minimized the damage induced by UVA irradiation in HDFs. Furthermore, western blot analysis demonstrated that Cur may attenuate UVA-induced ER stress, inflammation and apoptotic signaling by downregulating the protein expression of glucose-regulated protein 78, C/EBP-homologous protein, nuclear factor-κB and cleaved caspase-3, while upregulating the expression of Bcl-2. Additionally, it was demonstrated that Cur may regulate collagen metabolism by decreasing the protein expression of matrix metalloproteinase (MMP)-1 and MMP-3, and may promote the repair of cells damaged as a result of UVA irradiation through increasing the protein expression of transforming

Image-based modeling of radiation-induced foci

NASA Astrophysics Data System (ADS)

Costes, Sylvain; Cucinotta, Francis A.; Ponomarev, Artem; Barcellos-Hoff, Mary Helen; Chen, James; Chou, William; Gascard, Philippe

Several proteins involved in the response to DNA double strand breaks (DSB) form microscopically visible nuclear domains, or foci, after exposure to ionizing radiation. Radiation-induced foci (RIF) are believed to be located where DNA damage occurs. To test this assumption, we used Monte Carlo simulations to predict the spatial distribution of DSB in human nuclei exposed to high or low-LET radiation. We then compared these predictions to the distribution patterns of three DNA damage sensing proteins, i.e. 53BP1, phosphorylated ATM and γH2AX in human mammary epithelial. The probability to induce DSB can be derived from DNA fragment data measured experimentally by pulsed-field gel electrophoresis. We first used this probability in Monte Carlo simulations to predict DSB locations in synthetic nuclei geometrically described by a complete set of human chromosomes, taking into account microscope optics from real experiments. Simulations showed a very good agreement for high-LET, predicting 0.7 foci/µm along the path of a 1 GeV/amu Fe particle against measurement of 0.69 to 0.82 foci/µm for various RIF 5 min following exposure (LET 150 keV/µm). On the other hand, discrepancies were shown in foci frequency for low-LET, with measurements 20One drawback using a theoretical model for the nucleus is that it assumes a simplistic and static pattern for DNA densities. However DNA damage pattern is highly correlated to DNA density pattern (i.e. the more DNA, the more likely to have a break). Therefore, we generalized our Monte Carlo approach to real microscope images, assuming pixel intensity of DAPI in the nucleus was directly proportional to the amount of DNA in that pixel. With such approach we could predict DNA damage pattern in real images on a per nucleus basis. Since energy is randomly deposited along high-LET particle paths, RIF along these paths should also be randomly distributed. As expected, simulations produced DNA-weighted random (Poisson) distributions. In

Simultaneous detection of ultraviolet B-induced DNA damage using capillary electrophoresis with laser-induced fluorescence.

PubMed

Guthrie, Jeffrey W; Limmer, Robert T; Brooks, Eric A; Wisnewski, Chelsea C; Loggins-Davis, Nnekia D; Bouzid, Abderraouf

2015-01-01

An immunoassay based on CE-LIF was developed for the simultaneous detection of cyclobutane pyrimidine dimers (CPDs) and pyrimidine 6-4 pyrimidone photoproducts (6-4PPs) in genomic DNA irradiated with UVB or natural sunlight. Human cells were first exposed to varying amounts of UVB or natural sunlight to induce DNA damage. Genomic DNA was extracted and incubated with anti-CPD and anti-6-4PP primary antibodies attached to secondary antibodies with a fluorescent quantum dot (QD) reporter that emitted either red or yellow fluorescence. CE was used to separate the unbound antibodies from those bound to the photoproducts, and LIF with appropriate optical filters was used to separate the fluorescence signals from each QD to individual photomultiplier tubes for simultaneous photoproduct detection. Using this strategy, photoproducts were detected from ∼6 ng (200 ng μL(-1)) of DNA under a low UVB fluence of 65 J m(-2) for CPDs or 195 J m(-2) for 6-4PPs. This assay was also the first to demonstrate the detection of CPDs in human cells after only 15 min of irradiation under natural sunlight. Copyright © 2014 Elsevier B.V. All rights reserved.

Protective Effect of Chitin Urocanate Nanofibers against Ultraviolet Radiation

PubMed Central

Ito, Ikuko; Yoneda, Toshikazu; Omura, Yoshihiko; Osaki, Tomohiro; Ifuku, Shinsuke; Saimoto, Hiroyuki; Azuma, Kazuo; Imagawa, Tomohiro; Tsuka, Takeshi; Murahata, Yusuke; Ito, Norihiko; Okamoto, Yoshiharu; Minami, Saburo

2015-01-01

Urocanic acid is a major ultraviolet (UV)-absorbing chromophore. Chitins are highly crystalline structures that are found predominantly in crustacean shells. Alpha-chitin consists of microfibers that contain nanofibrils embedded in a protein matrix. Acid hydrolysis is a common method used to prepare chitin nanofibrils (NFs). We typically obtain NFs by hydrolyzing chitin with acetic acid. However, in the present study, we used urocanic acid to prepare urocanic acid chitin NFs (UNFs) and examined its protective effect against UVB radiation. Hos: HR-1 mice coated with UNFs were UVB irradiated (302 nm, 150 mJ/cm2), and these mice showed markedly lower UVB radiation-induced cutaneous erythema than the control. Additionally, sunburn cells were rarely detected in the epidermis of UNFs-coated mice after UVB irradiation. Although the difference was not as significant as UNFs, the number of sunburn cells in mice treated with acetic acid chitin nanofibrils (ANFs) tended to be lower than in control mice. These results demonstrate that ANFs have a protective effect against UVB and suggest that the anti-inflammatory and antioxidant effects of NFs influence the protective effect of ANFs against UVB radiation. The combination of NFs with other substances that possess UV-protective effects, such as urocanic acid, may provide an enhanced protective effect against UVB radiation. PMID:26703629

Low-Energy Electron-Induced Strand Breaks in Telomere-Derived DNA Sequences-Influence of DNA Sequence and Topology.

PubMed

Rackwitz, Jenny; Bald, Ilko

2018-03-26

During cancer radiation therapy high-energy radiation is used to reduce tumour tissue. The irradiation produces a shower of secondary low-energy (<20 eV) electrons, which are able to damage DNA very efficiently by dissociative electron attachment. Recently, it was suggested that low-energy electron-induced DNA strand breaks strongly depend on the specific DNA sequence with a high sensitivity of G-rich sequences. Here, we use DNA origami platforms to expose G-rich telomere sequences to low-energy (8.8 eV) electrons to determine absolute cross sections for strand breakage and to study the influence of sequence modifications and topology of telomeric DNA on the strand breakage. We find that the telomeric DNA 5'-(TTA GGG) 2 is more sensitive to low-energy electrons than an intermixed sequence 5'-(TGT GTG A) 2 confirming the unique electronic properties resulting from G-stacking. With increasing length of the oligonucleotide (i.e., going from 5'-(GGG ATT) 2 to 5'-(GGG ATT) 4 ), both the variety of topology and the electron-induced strand break cross sections increase. Addition of K + ions decreases the strand break cross section for all sequences that are able to fold G-quadruplexes or G-intermediates, whereas the strand break cross section for the intermixed sequence remains unchanged. These results indicate that telomeric DNA is rather sensitive towards low-energy electron-induced strand breakage suggesting significant telomere shortening that can also occur during cancer radiation therapy. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Effect of ultraviolet radiation on ALDH1 expression in human lens epithelial cells].

PubMed

Shi, Jingming; Jia, Songbai; Chen, Xuan; Tang, Luosheng

2012-06-01

To determine the apoptosis-inducing effect of ultraviolet light (UV) on human lens epithelial cell (HLEC) and to explore the involvement of changes in ALDH1 folowing UV radiation. HLEC was exposed to the same UV light source and was subsequently divided into 6 groups according to UV radiation time of 0 (control group), 5, 10, 15, and 30 min. Apoptosis was detected by AO/EB staining. Changes of ALDH1 in HLEC were detected by immunohistochemical staining and Western blot. The intensity of immunohistochemical staining and the rate of positive cells decreased with increase of UV time (P<0.05). The rate of positive ALDH1 cells was negatively correlated with the rate of apoptosis (r= -0.92, P<0.05). Western blot showed the integrated absorbance values significantly decreased with the increase of UV time (P<0.05). ALDH1 in HLEC decreases with an increase of UV exposure, which may be related to UV induced apoptosis of HLEC.

Preventive effect of ultraviolet radiation on murine chronic sclerodermatous graft-versus-host disease.

PubMed

Mermet, Isabelle; Kleinclauss, François; Marandin, Aliette; Guérrini, Jean Sébastien; Angonin, Régis; Tiberghien, Pierre; Saas, Philippe; Aubin, François

2007-12-27

Although previous studies have demonstrated the efficient modulatory effects of ultraviolet radiation B (UVB) on cutaneous graft-versus-host disease (GVHD), most animal research on GVHD has been performed in murine models of acute GVHD. Here, we studied the preventive effect of UVB radiation on the occurrence of chronic sclerodermatous (Scl) GVHD in a murine model. Scl GVHD was induced by transplanting lethally irradiated BALB/c mice with B10.D2 bone marrow and spleen cells. Recipient mice were exposed to UVB before or after bone marrow and spleen cell infusion. Histological and clinical evaluation of GVHD was performed, in association with the characterization of epidermal Langerhans cells. UVB irradiation of recipients after, and more remarkably before, transplantation induced a decrease of Scl GVHD severity associated with epidermal Langerhans cells depletion. We conclude that UVB irradiation of recipient before or after transplantation has a preventive effect on cutaneous Scl GVHD and may represent an effective strategy for prevention of Scl GVHD.

Electromagnetic noise inhibits radiofrequency radiation-induced DNA damage and reactive oxygen species increase in human lens epithelial cells

PubMed Central

Wu, Wei; Wang, KaiJun; Ni, Shuang; Ye, PanPan; Yu, YiBo; Ye, Juan; Sun, LiXia

2008-01-01

Purpose The goal of this study was to investigate whether superposing of electromagnetic noise could block or attenuate DNA damage and intracellular reactive oxygen species (ROS) increase of cultured human lens epithelial cells (HLECs) induced by acute exposure to 1.8 GHz radiofrequency field (RF) of the Global System for Mobile Communications (GSM). Methods An sXc-1800 RF exposure system was used to produce a GSM signal at 1.8 GHz (217 Hz amplitude-modulated) with the specific absorption rate (SAR) of 1, 2, 3, and 4 W/kg. After 2 h of intermittent exposure, the ROS level was assessed by the fluorescent probe, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). DNA damage to HLECs was examined by alkaline comet assay and the phosphorylated form of histone variant H2AX (γH2AX) foci formation assay. Results After exposure to 1.8 GHz RF for 2 h, HLECs exhibited significant intracellular ROS increase in the 2, 3, and 4 W/kg groups. RF radiation at the SAR of 3 W/kg and 4 W/kg could induce significant DNA damage, examined by alkaline comet assay, which was used to detect mainly single strand breaks (SSBs), while no statistical difference in double strand breaks (DSBs), evaluated by γH2AX foci, was found between RF exposure (SAR: 3 and 4 W/kg) and sham exposure groups. When RF was superposed with 2 μT electromagnetic noise could block RF-induced ROS increase and DNA damage. Conclusions DNA damage induced by 1.8 GHz radiofrequency field for 2 h, which was mainly SSBs, may be associated with the increased ROS production. Electromagnetic noise could block RF-induced ROS formation and DNA damage. PMID:18509546

TAO kinases mediate activation of p38 in response to DNA damage

PubMed Central

Raman, Malavika; Earnest, Svetlana; Zhang, Kai; Zhao, Yingming; Cobb, Melanie H

2007-01-01

Thousand and one amino acid (TAO) kinases are Ste20p-related MAP kinase kinase kinases (MAP3Ks) that activate p38 MAPK. Here we show that the TAO kinases mediate the activation of p38 in response to various genotoxic stimuli. TAO kinases are activated acutely by ionizing radiation, ultraviolet radiation, and hydroxyurea. Full-length and truncated fragments of dominant negative TAOs inhibit the activation of p38 by DNA damage. Inhibition of TAO expression by siRNA also decreases p38 activation by these agents. Cells in which TAO kinases have been knocked down are less capable of engaging the DNA damage-induced G2/M checkpoint and display increased sensitivity to IR. The DNA damage kinase ataxia telangiectasia mutated (ATM) phosphorylates TAOs in vitro; radiation induces phosphorylation of TAO on a consensus site for phosphorylation by the ATM protein kinase in cells; and TAO and p38 activation is compromised in cells from a patient with ataxia telangiectasia that lack ATM. These findings indicate that TAO kinases are regulators of p38-mediated responses to DNA damage and are intermediates in the activation of p38 by ATM. PMID:17396146

DNA Damage in Bone Marrow Cells Induced by Femtosecond and Nanosecond Ultraviolet Laser Pulses.

PubMed

Morkunas, Vaidotas; Gabryte, Egle; Vengris, Mikas; Danielius, Romualdas; Danieliene, Egle; Ruksenas, Osvaldas

2015-12-01

The purpose of this study was to investigate the possible genotoxic impact of new generation 205 nm femtosecond solid-state laser irradiation on the DNA of murine bone marrow cells in vitro, and to compare the DNA damage caused by both femtosecond and nanosecond UV laser pulses. Recent experiments of corneal stromal ablation in vitro and in vivo applying femtosecond UV pulses showed results comparable with or superior to those obtained using nanosecond UV lasers. However, the possible genotoxic effect of ultrashort laser pulses was not investigated. Mouse bone marrow cells were exposed to different doses of 205 nm femtosecond, 213 and 266 nm nanosecond lasers, and 254 nm UV lamp irradiation. The comet assay was used for the evaluation of DNA damage. All types of irradiation demonstrated intensity-dependent genotoxic impact. The DNA damage induced depended mainly upon wavelength rather than on other parameters such as pulse duration, repetition rate, or beam delivery to a target. Both 205 nm femtosecond and clinically applied 213 nm nanosecond lasers' pulses induced a comparable amount of DNA breakage in cells exposed to the same irradiation dose. To further evaluate the suitability of femtosecond UV laser sources for microsurgery, a separate investigation of the genotoxic and mutagenic effects on corneal cells in vitro and, particularly, in vivo is needed.

Radiation-induced DNA damage and the relative biological effectiveness of 18F-FDG in wild-type mice

DOE PAGES

Taylor, Kristina; Lemon, Jennifer A.; Boreham, Douglas R.

2014-05-28

Clinically, the most commonly used positron emission tomography (PET) radiotracer is the glucose analog 2-[ 18F] fluoro-2-deoxy-d-glucose ( 18F-FDG), however little research has been conducted on the biological effects of 18F-FDG injections. The induction and repair of DNA damage and the relative biological effectiveness (RBE) of radiation from 18F-FDG relative to 662 keV γ-rays were investigated. The study also assessed whether low-dose radiation exposure from 18F-FDG was capable of inducing an adaptive response. DNA damage to the bone marrow erythroblast population was measured using micronucleus formation and lymphocyte γH2A.X levels. To test the RBE of 18F-FDG, mice were injected withmore » a range of activities of 18F-FDG (0–14.80 MBq) or irradiated with Cs-137 γ-rays (0–100 mGy). The adaptive response was investigated 24 h after the 18F-FDG injection by 1 Gy in vivo challenge doses for micronucleated reticulocyte (MN-RET) formation or 1, 2 and 4 Gy in vitro challenges doses for γH2A.X formation. A significant increase in MN-RET formation above controls occurred following injection activities of 3.70, 7.40 or 14.80 MBq (P < 0.001) which correspond to bone marrow doses of ~35, 75 and 150 mGy, respectively. Per unit dose, the Cs-137 radiation exposure induced significantly more damage than the 18F-FDG injections (RBE = 0.79 ± 0.04). A 20% reduction in γH2A.X fluorescence was observed in mice injected with a prior adapting low dose of 14.80 MBq 18F-FDG relative to controls (P < 0.019). A 0.74 MBq 18F-FDG injection, which gives mice a dose approximately equal to a typical human PET scan, did not cause a significant increase in DNA damage nor did it generate an adaptive response. Typical 18F-FDG injection activities used in small animal imaging (14.80 MBq) resulted in a decrease in DNA damage, as measured by γH2A.X formation, below spontaneous levels observed in control mice. Lastly, the 18F-FDG RBE was <1.0, indicating that the mixed radiation quality

Radiation-induced DNA damage and the relative biological effectiveness of 18F-FDG in wild-type mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, Kristina; Lemon, Jennifer A.; Boreham, Douglas R.

Clinically, the most commonly used positron emission tomography (PET) radiotracer is the glucose analog 2-[ 18F] fluoro-2-deoxy-d-glucose ( 18F-FDG), however little research has been conducted on the biological effects of 18F-FDG injections. The induction and repair of DNA damage and the relative biological effectiveness (RBE) of radiation from 18F-FDG relative to 662 keV γ-rays were investigated. The study also assessed whether low-dose radiation exposure from 18F-FDG was capable of inducing an adaptive response. DNA damage to the bone marrow erythroblast population was measured using micronucleus formation and lymphocyte γH2A.X levels. To test the RBE of 18F-FDG, mice were injected withmore » a range of activities of 18F-FDG (0–14.80 MBq) or irradiated with Cs-137 γ-rays (0–100 mGy). The adaptive response was investigated 24 h after the 18F-FDG injection by 1 Gy in vivo challenge doses for micronucleated reticulocyte (MN-RET) formation or 1, 2 and 4 Gy in vitro challenges doses for γH2A.X formation. A significant increase in MN-RET formation above controls occurred following injection activities of 3.70, 7.40 or 14.80 MBq (P < 0.001) which correspond to bone marrow doses of ~35, 75 and 150 mGy, respectively. Per unit dose, the Cs-137 radiation exposure induced significantly more damage than the 18F-FDG injections (RBE = 0.79 ± 0.04). A 20% reduction in γH2A.X fluorescence was observed in mice injected with a prior adapting low dose of 14.80 MBq 18F-FDG relative to controls (P < 0.019). A 0.74 MBq 18F-FDG injection, which gives mice a dose approximately equal to a typical human PET scan, did not cause a significant increase in DNA damage nor did it generate an adaptive response. Typical 18F-FDG injection activities used in small animal imaging (14.80 MBq) resulted in a decrease in DNA damage, as measured by γH2A.X formation, below spontaneous levels observed in control mice. Lastly, the 18F-FDG RBE was <1.0, indicating that the mixed radiation quality

Comprehensive Review of Ultraviolet Radiation and the Current Status on Sunscreens

PubMed Central

Moon, Summer; Armstrong, Frank

2012-01-01

In the past, manufacturers’ labeling of sunscreen varied greatly, confusing the consumers regarding efficacy and the appropriate photoprotection provided by their products. Therefore, in June 2011, the United States Food and Drug Administration issued new guidelines for sunscreen labeling. Sunscreen products are over-the-counter drugs; therefore, they are regulated by the United States Food and Drug Administration to determine safety, efficacy, and labeling. This article discusses ultraviolet radiation and the positive and negative effects of ultraviolet radiation, provides a review of sunscreens, and discusses the new United States Food and Drug Administration regulations for sunscreens. PMID:23050030

Track structure based modelling of light ion radiation effects on nuclear and mitochondrial DNA

NASA Astrophysics Data System (ADS)

Schmitt, Elke; Ottolenghi, Andrea; Dingfelder, Michael; Friedland, Werner; Kundrat, Pavel; Baiocco, Giorgio

2016-07-01

Space radiation risk assessment is of great importance for manned spaceflights in order to estimate risks and to develop counter-measures to reduce them. Biophysical simulations with PARTRAC can help greatly to improve the understanding of initial biological response to ionizing radiation. Results from modelling radiation quality dependent DNA damage and repair mechanisms up to chromosomal aberrations (e.g. dicentrics) can be used to predict radiation effects depending on the kind of mixed radiation field exposure. Especially dicentric yields can serve as a biomarker for an increased risk due to radiation and hence as an indicator for the effectiveness of the used shielding. PARTRAC [1] is a multi-scale biophysical research MC code for track structure based initial DNA damage and damage response modelling. It integrates physics, radiochemistry, detailed nuclear DNA structure and molecular biology of DNA repair by NHEJ-pathway to assess radiation effects on cellular level [2]. Ongoing experiments with quasi-homogeneously distributed compared to sub-micrometre focused bunches of protons, lithium and carbon ions allow a separation of effects due to DNA damage complexity on nanometre scale from damage clustering on (sub-) micrometre scale [3, 4]. These data provide an unprecedented benchmark for the DNA damage response model in PARTRAC and help understand the mechanisms leading to cell killing and chromosomal aberrations (e.g. dicentrics) induction. A large part of space radiation is due to a mixed ion field of high energy protons and few heavier ions that can be only partly absorbed by the shielding. Radiation damage induced by low-energy ions significantly contributes to the high relative biological efficiency (RBE) of ion beams around Bragg peak regions. For slow light ions the physical cross section data basis in PARTRAC has been extended to investigate radiation quality effects in the Bragg peak region [5]. The resulting range and LET values agree with ICRU data

Detection of ultraviolet radiation using tissue equivalent radiochromic gel materials

NASA Astrophysics Data System (ADS)

Bero, M. A.; Abukassem, I.

2009-05-01

Ferrous Xylenol-orange Gelatin gel (FXG) is known to be sensitive to ionising radiation such as γ and X-rays. The effect of ionising radiation is to produce an increase in the absorption over a wide region of the visible spectrum, which is proportional to the absorbed dose. This study demonstrates that FXG gel is sensitive to ultraviolet radiation and therefore it could functions as UV detector. Short exposure to UV radiation produces linear increase in absorption measured at 550nm, however high doses of UV cause the ion indicator colour to fad away in a manner proportional to the incident UV energy. Light absorbance increase at the rate of 1.1% per minute of irradiation was monitored. The exposure level at which the detector has linear response is comparable to the natural summer UV radiation. Evaluating the UV ability to pass through tissue equivalent gel materials shows that most of the UV gets absorbed in the first 5mm of the gel materials, which demonstrate the damaging effects of this radiation type on human skin and eyes. It was concluded that FXG gel dosimeter has the potential to offer a simple, passive ultraviolet radiation detector with sensitivity suitable to measure and visualises the natural sunlight UV exposure directly by watching the materials colour changes.

CHARACTERIZATION OF RELATIVE SENSITIVITY OF AMPHIBIANS TO ULTRAVIOLET RADIATION

EPA Science Inventory

Different studies have demonstrated that solar ultraviolet (UV) radiation can adversely affect survival and development of embryonic and larval amphibians. However, because of among-laboratory variations in exposure profiles (artificial vs. natural sunlight; natural sunlight at d...

DNA Topoisomerase IB as a Potential Ionizing Radiation Exposure and Dose Biomarker.

PubMed

Daudee, Rotem; Gonen, Rafi; German, Uzi; Orion, Itzhak; Alfassi, Zeev B; Priel, Esther

2018-06-01

In radiation exposure scenarios where physical dosimetry is absent or inefficient, dose estimation must rely on biological markers. A reliable biomarker is of utmost importance in correlating biological system changes with radiation exposure. Human DNA topoisomerase ІB (topo І) is a ubiquitous nuclear enzyme, which is involved in essential cellular processes, including transcription, DNA replication and DNA repair, and is the target of anti-cancer drugs. It has been shown that the cellular activity of this enzyme is significantly sensitive to various DNA lesions, including radiation-induced DNA damages. Therefore, we investigated the potential of topo I as a biomarker of radiation exposure and dose. We examined the effect of exposure of different human cells to beta, X-ray and gamma radiation on the cellular catalytic activity of topo I. The results demonstrate a significant reduction in the DNA relaxation activity of topo I after irradiation and the level of the reduction was correlated with radiation dose. In normal human peripheral blood lymphocytes, exposure for 3 h to an integral dose of 0.065 mGy from tritium reduced the enzyme activity to less than 25%. In MG-63 osteoblast-like cells and in human pulmonary fibroblast (HPF) cells exposed to gamma radiation from a 60 Co source (up to 2 Gy) or to X rays (up to 2.8 Gy), a significant decrease in topo I catalytic activity was also observed. We observed that the enzyme-protein level was not altered but was partially posttranslational modified by ADP-ribosylation of the enzyme protein that is known to reduce topo I activity. The results of this study suggest that the decrease in the cellular topo I catalytic activity after low-dose exposure to different radiation types may be considered as a novel biomarker of ionizing radiation exposure and dose. For this purpose, a suitable ELISA-based method for large-scale analysis of radiation-induced topo I modification is under development.

Ultraviolet-B radiation induced crosslinking improves physical properties of cold- and warm-water fish gelatin gels and films

USDA-ARS?s Scientific Manuscript database

Cold- and warm-water fish gelatin granules were exposed to ultraviolet-B radiation for doses up to 29.7 J/cm2. Solutions and films were prepared from the granules. Gel electrophoresis and refractive index were used to examine changes in molecular weight of the samples. Also, the gel strength and rhe...

Ultraviolet Radiation Induction of Mutation in Penicillium Claviforme.

ERIC Educational Resources Information Center

New, June; Jolley, Ray

1986-01-01

Cites reasons why Penicillium claviforme is an exceptionally good species for ultraviolet induced mutation experiments. Provides a set of laboratory instructions for teachers and students. Includes a discussion section. (ML)

The budget of biologically active ultraviolet radiation in the earth-atmosphere system

NASA Technical Reports Server (NTRS)

Frederick, John E.; Lubin, Dan

1988-01-01

This study applies the concept of a budget to describe the interaction of solar ultraviolet (UV) radiation with the earth-atmosphere system. The wavelength ranges of interest are the biologically relevant UV-B between 280 and 320 nm and the UV-A from 32000 to 400 nm. The Nimbus 7 solar backscattered ultraviolet (SBUV) instrument provides measurements of total column ozone and information concerning cloud cover which, in combination with a simple model of radiation transfer, define the fractions of incident solar irradiance absorbed in the atmosphere, reflected to space, and absorbed at the ground. Results for the month of July quantify the contribution of fractional cloud cover and cloud optical thickness to the radiation budget's three components. Scattering within a thick cloud layer makes the downward radiation field at the cloud base more isotropic than is the case for clear skies. For small solar zenith angles, typical of summer midday conditions, the effective pathlength of this diffuse irradiance through tropospheric ozone is greater than that under clear-sky conditions. The result is an enhanced absorption of UV-B radiation in the troposphere during cloud-covered conditions. Major changes in global cloud cover or cloud optical thicknesses could alter the ultraviolet radiation received by the biosphere by an amount comparable to that predicted for long-term trends in ozone.

Monte Carlo simulation of ionizing radiation induced DNA strand breaks utilizing coarse grained high-order chromatin structures.

PubMed

Liang, Ying; Yang, Gen; Liu, Feng; Wang, Yugang

2016-01-07

Ionizing radiation threatens genome integrity by causing DNA damage. Monte Carlo simulation of the interaction of a radiation track structure with DNA provides a powerful tool for investigating the mechanisms of the biological effects. However, the more or less oversimplification of the indirect effect and the inadequate consideration of high-order chromatin structures in current models usually results in discrepancies between simulations and experiments, which undermine the predictive role of the models. Here we present a biophysical model taking into consideration factors that influence indirect effect to simulate radiation-induced DNA strand breaks in eukaryotic cells with high-order chromatin structures. The calculated yields of single-strand breaks and double-strand breaks (DSBs) for photons are in good agreement with the experimental measurements. The calculated yields of DSB for protons and α particles are consistent with simulations by the PARTRAC code, whereas an overestimation is seen compared with the experimental results. The simulated fragment size distributions for (60)Co γ irradiation and α particle irradiation are compared with the measurements accordingly. The excellent agreement with (60)Co irradiation validates our model in simulating photon irradiation. The general agreement found in α particle irradiation encourages model applicability in the high linear energy transfer range. Moreover, we demonstrate the importance of chromatin high-order structures in shaping the spectrum of initial damage.

Immunofluorescent Detection of DNA Double Strand Breaks induced by High-LET Radiation

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Wu, Honglu; Desai, Nirav

2004-01-01

Within cell nuclei, traversing charged heavy ion particles lead to the accumulation of proteins related to DNA lesions and repair along the ion trajectories. Irradiation using a standard geometric setup with the beam path perpendicular to the cell monolayer generates discrete foci of several proteins known to localize at sites of DNA double strand breaks (DSBs). One such molecule is the histone protein H2AX (gamma-H2AX), which gets rapidly phosphorylated in response to ionizing radiation. Here we present data obtained with a modified irradiation geometry characterized by a beam path parallel to a monolayer of human fibroblast cells. This new irradiation geometry leads to the formation of gamma-H2AX aggregates in the shape of streaks stretching over several micrometers in the x/y plane, thus enabling the analysis of the fluorescence distributions along the particle trajectories. Qualitative analysis of these distributions presented insights into the DNA repair kinetics along the primary track structure and visualization of possible chromatin movement. We also present evidence of colocalization of gamma-H2AX with several other proteins in responses to ionizing radiation exposure. Analysis of gamma-H2AX has the potential to provide useful information on human cell responses to high LET radiation after exposure to space-like radiation.

Day and night variations in the repair of ionizing-radiation-induced DNA damage in mouse splenocytes.

PubMed

Palombo, Philipp; Moreno-Villanueva, Maria; Mangerich, Aswin

2015-04-01

In mammals, biological rhythms synchronize physiological and behavioral processes to the 24-h light-dark (LD) cycle. At the molecular level, self-sustaining processes, such as oscillations of transcription-translation feedback loops, control the circadian clock, which in turn regulates a wide variety of cellular processes, including gene expression and cell cycle progression. Furthermore, previous studies reported circadian oscillations in the repair capacity of DNA lesions specifically repaired by nucleotide excision repair (NER). However, it is so far only poorly understood if DNA repair pathways other than NER are under circadian control, in particular base excision and DNA strand break repair. In the present study, we analyzed potential day and night variations in the repair of DNA lesions induced by ionizing radiation (i.e., mainly oxidative damage and DNA strand breaks) in living mouse splenocytes using a modified protocol of the automated FADU assay. Our results reveal that splenocytes isolated from mice during the light phase (ZT06) displayed higher DNA repair activity than those of the dark phase (ZT18). As analyzed by highly sensitive and accurate qPCR arrays, these alterations were accompanied by significant differences in expression profiles of genes involved in the circadian clock and DNA repair. Notably, the majority of the DNA repair genes were expressed at higher levels during the light phase (ZT06). This included genes of all major DNA repair pathways with the strongest differences observed for genes of base excision and DNA double strand break repair. In conclusion, here we provide novel evidence that mouse splenocytes exhibit significant differences in the repair of IR-induced DNA damage during the LD cycle, both on a functional and on a gene expression level. It will be interesting to test if these findings could be exploited for therapeutic purposes, e.g. time-of-the-day-specific application of DNA-damaging treatments used against blood

Hypersensitivity of skin fibroblasts from basal cell nevus syndrome patients to killing by ultraviolet B but not by ultraviolet C radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Applegate, L.A.; Goldberg, L.H.; Ley, R.D.

Basal cell nevus syndrome (BCNS) is an autosomal dominant genetic disorder in which the afflicted individuals are extremely susceptible to sunlight-induced skin cancers, particularly basal cell carcinomas. However, the cellular and molecular basis for BCNS is unknown. To ascertain whether there is any relationship between genetic predisposition to skin cancer and increased sensitivity of somatic cells from BCNS patients to killing by UV radiation, we exposed skin fibroblasts established from unexposed skin biopsies of several BCNS and age- and sex-matched normal individuals to either UV-B (280-320 nm) or UV-C (254 nm) radiation and determined their survival. The results indicated thatmore » skin fibroblasts from BCNS patients were hypersensitive to killing by UV-B but not UV-C radiation as compared to skin fibroblasts from normal individuals. DNA repair studies indicated that the increased sensitivity of BCNS skin fibroblasts to killing by UV-B radiation was not due to a defect in the excision repair of pyrimidine dimers. These results indicate that there is an association between hypersensitivity of somatic cells to killing by UV-B radiation and the genetic predisposition to skin cancer in BCNS patients. In addition, these results suggest that DNA lesions (and repair processes) other than the pyrimidine dimer are also involved in the pathogenesis of sunlight-induced skin cancers in BCNS patients. More important, the UV-B sensitivity assay described here may be used as a diagnostic tool to identify presymptomatic individuals with BCNS.« less

Dependence on radiation quality of DNA fragmentation spectra

NASA Astrophysics Data System (ADS)

Campa, Alessandro; Ottolenghi, Andrea; Alloni, Daniele; Ballarini, Francesca; Belli, Mauro; Esposito, Giuseppe; Facoetti, Angelica; Friedland, Werner; Liotta, Marco; Paretzke, Herwig

Energy deposition by radiation initially gives rise to cellular critical lesions such as DNA doublestrand breaks (DSB), that later lead to the formation of relevant biological endpoints. Studies on fragment size distributions induced by radiations of various qualities can be of great help in linking the characteristics of radiation to cellular endpoints, providing information for understanding the main mechanisms of cell damage. Here we are concerned with the damage induced by heavy charged particles; this issue is very important in the field of radioprotection of astronauts participating in long term space missions, besides being relevant also in other fields, like hadrontherapy. Galactic Cosmic Rays contain a large component of high-LET particles (HZE), e.g. helium and carbon ions, as well as highcharge particles such as iron ions. These particles are characterized by complex track structures with energy depositions not only along the path of the primary particle, but also at relatively large distance form the path, due to the presence of high energy secondary electrons. In this work we have simulated the irradiation of human fibroblasts with γ-rays, protons, helium, carbon and iron ions at a fixed dose with the biophysical Monte Carlo code PARTRAC,and calculated the induction of DSB. The PARTRAC code includes accurate representation of the chromatin geometry and of the physical and physico-chemical processes associated with the energy deposition by radiation. The results of a first validation of the code have been reported in A. Campa et al. (2005) and D. Alloni et al. (2007a, 2007b). DNA fragment spectra were calculated based on the DSB induction patterns and compared in particular for particles of the same specific energy and for particles of the same LET. Special emphasis has been directed to the calculation of very small fragments (< 1 kbp) that are not detectable by the most common experimental techniques and that can significantly influence the RBE

Ultraviolet radiation properties as applied to photoclimatherapy at the Dead Sea.

PubMed

Kudish, A I; Abels, D; Harari, M

2003-05-01

The Dead Sea basin, the lowest terrestrial point on earth, is recognized as a natural treatment center for patients with various cutaneous and rheumatic diseases. Psoriasis is the major skin disease treated at the Dead Sea with excellent improvement to complete clearance exceeding 85% after 4 weeks of treatment. These results were postulated to be associated with a unique spectrum of ultraviolet radiation present in the Dead Sea area. The UVB and UVA radiation at two sites is measured continuously by identical sets of broad-band Solar Light Co. Inc. meters (Philadelphia, PA). The spectral selectivity within the UVB and UVA spectrum was determined using a narrow-band spectroradiometer, UV-Optronics 742 (Orlando, FL). The optimum exposure time intervals for photoclimatherapy, defined as the minimum ratio of erythema to therapeutic radiation intensities, were also determined using a Solar Light Co. Inc. Microtops II, Ozone Monitor-Sunphotometer. The ultraviolet radiation at the Dead Sea is attenuated relative to Beer Sheva as a result of the increased optical path length and consequent enhanced scattering. The UVB radiation is attenuated to a greater extent than UVA and the shorter erythema UVB spectral range decreased significantly compared with the longer therapeutic UVB wavelengths. It was demonstrated that the relative attenuation within the UVB spectral range is greatest for the shorter erythema rays and less for the longer therapeutic UVB wavelengths, thus producing a greater proportion of the longer therapeutic UVB wavelengths in the ultraviolet spectrum. These measurements can be utilized to minimize the exposure to solar radiation by correlating the cumulative UVB radiation dose to treatment efficacy and by formulating a patient sun exposure treatment protocol for Dead Sea photoclimatherapy.

Radiation track, DNA damage and response—a review

NASA Astrophysics Data System (ADS)

Nikjoo, H.; Emfietzoglou, D.; Liamsuwan, T.; Taleei, R.; Liljequist, D.; Uehara, S.

2016-11-01

The purpose of this paper has been to review the current status and progress of the field of radiation biophysics, and draw attention to the fact that physics, in general, and radiation physics in particular, with the aid of mathematical modeling, can help elucidate biological mechanisms and cancer therapies. We hypothesize that concepts of condensed-matter physics along with the new genomic knowledge and technologies and mechanistic mathematical modeling in conjunction with advances in experimental DNA (Deoxyrinonucleic acid molecule) repair and cell signaling have now provided us with unprecedented opportunities in radiation biophysics to address problems in targeted cancer therapy, and genetic risk estimation in humans. Obviously, one is not dealing with ‘low-hanging fruit’, but it will be a major scientific achievement if it becomes possible to state, in another decade or so, that we can link mechanistically the stages between the initial radiation-induced DNA damage; in particular, at doses of radiation less than 2 Gy and with structural changes in genomic DNA as a precursor to cell inactivation and/or mutations leading to genetic diseases. The paper presents recent development in the physics of radiation track structure contained in the computer code system KURBUC, in particular for low-energy electrons in the condensed phase of water for which we provide a comprehensive discussion of the dielectric response function approach. The state-of-the-art in the simulation of proton and carbon ion tracks in the Bragg peak region is also presented. The paper presents a critical discussion of the models used for elastic scattering, and the validity of the trajectory approach in low-electron transport. Brief discussions of mechanistic and quantitative aspects of microdosimetry, DNA damage and DNA repair are also included as developed by the authors’ work.

FTS is responsible for radiation-induced nuclear phosphorylation of EGFR and repair of DNA damage in cervical cancer cells.

PubMed

Muthusami, Sridhar; Prabakaran, D S; Yu, Jae-Ran; Park, Woo-Yoon

2015-02-01

Radiation-induced nuclear stabilization and phosphorylation of epidermal growth factor receptor (EGFR) confers radioresistance. Understanding of the factor(s) regulating the nuclear stabilization and phosphorylation of EGFR is important for the modulation of radioresistance. Present study was designed to delineate the regulation of EGFR nuclear stabilization and phosphorylation by fused toes homolog (FTS), an oncoprotein, which is responsible for the radioresistance in cervical cancer cells. A cervical cancer cell line, ME180 was used. Radiation-induced change in the levels of EGFR, p-EGFR and FTS were evaluated in the cytoplasm and nucleus using Western blot analyses. FTS was silenced using siRNA-based approach. Interaction between EGFR and FTS was assessed using immunofluorescence and immunoprecipitation analyses. Double-strand breaks (DSB) of DNA were assessed using γ H2AX. Radiation increased the levels of EGFR and FTS in the cytoplasm and nucleus. EGFR and FTS are in physical association with each other and are co-localized in the cells. FTS silencing largely reduced the nuclear stabilization and phosphorylation of EGFR and DNA-protein kinase along with increased initial and residual DSBs. EGFR and FTS physically associate with each other and FTS silencing radiosensitizes ME180 cells through impaired nuclear EGFR signaling.

DNA Damage by Ionizing Radiation: Tandem Double Lesions by Charged Particles

NASA Technical Reports Server (NTRS)

Huo, Winifred M.; Chaban, Galina M.; Wang, Dunyou; Dateo, Christopher E.

2005-01-01

Oxidative damages by ionizing radiation are the source of radiation-induced carcinogenesis, damage to the central nervous system, lowering of the immune response, as well as other radiation-induced damages to human health. Monte Carlo track simulations and kinetic modeling of radiation damages to the DNA employ available molecular and cellular data to simulate the biological effect of high and low LET radiation io the DNA. While the simulations predict single and double strand breaks and base damages, so far all complex lesions are the result of stochastic coincidence from independent processes. Tandem double lesions have not yet been taken into account. Unlike the standard double lesions that are produced by two separate attacks by charged particles or radicals, tandem double lesions are produced by one single attack. The standard double lesions dominate at the high dosage regime. On the other hand, tandem double lesions do not depend on stochastic coincidences and become important at the low dosage regime of particular interest to NASA. Tandem double lesions by hydroxyl radical attack of guanine in isolated DNA have been reported at a dosage of radiation as low as 10 Gy. The formation of two tandem base lesions was found to be linear with the applied doses, a characteristic of tandem lesions. However, tandem double lesions from attack by a charged particle have not been reported.

SUMER: Solar Ultraviolet Measurements of Emitted Radiation

NASA Technical Reports Server (NTRS)

Wilhelm, K.; Axford, W. I.; Curdt, W.; Gabriel, A. H.; Grewing, M.; Huber, M. C. E.; Jordan, S. D.; Kuehne, M.; Lemaire, P.; Marsch, E.

1992-01-01

The experiment Solar Ultraviolet Measurements of Emitted Radiation (SUMER) is designed for the investigations of plasma flow characteristics, turbulence and wave motions, plasma densities and temperatures, structures and events associated with solar magnetic activity in the chromosphere, the transition zone and the corona. Specifically, SUMER will measure profiles and intensities of Extreme Ultraviolet (EUV) lines emitted in the solar atmosphere ranging from the upper chromosphere to the lower corona; determine line broadenings, spectral positions and Doppler shifts with high accuracy, provide stigmatic images of selected areas of the Sun in the EUV with high spatial, temporal and spectral resolution and obtain full images of the Sun and the inner corona in selectable EUV lines, corresponding to a temperature from 10,000 to more than 1,800,000 K.

Measurements of Solar Ultraviolet Radiation Exposure at Work and at Leisure in Danish Workers.

PubMed

Grandahl, Kasper; Eriksen, Paul; Ibler, Kristina Sophie; Bonde, Jens Peter; Mortensen, Ole Steen

2018-03-30

Exposure to solar ultraviolet radiation is the main cause of skin cancer and may well present an occupational health and safety problem. In Denmark, skin cancer is a common disease in the general population, but detailed data on solar ultraviolet radiation exposure among outdoor workers are lacking. The aim of this study was to provide objective measurements of solar ultraviolet radiation exposure on working days and at leisure and compare levels of exposure between groups of mainly outdoor, equal-parts-outdoor-and-indoor and indoor workers. To this end, UV-B dosimeters with an aluminum gallium nitride (AlGaN) photodiode detector were used to measure the solar ultraviolet radiation exposure of 457 workers in the Danish summer season. Presented as semi-annual standard erythemal dose (SED) on working days, respectively, at leisure, the results are for mainly outdoor workers 214.2 SED and 64.8 SED, equal-parts-outdoor-and-indoor workers 131.4 SED and 64.8 SED, indoor workers 55.8 SED and 57.6 SED. The daily SED by month is significantly different (α = 0.05) between mainly outdoor, equal-parts-outdoor-and-indoor and indoor workers and across professional groups; some of which are exposed at very high levels that is roofers 361.8 SED. These findings substantiate that exposure to solar ultraviolet radiation is indeed an occupational health and safety problem in Denmark. © 2018 The Authors. Photochemistry and Photobiology published by Wiley Periodicals, Inc. on behalf of American Society for Photobiology.

Stage-dependent teratogenic and lethal effects exerted by ultraviolet B radiation on Rhinella (Bufo) arenarum embryos.

PubMed

Castañaga, Luis A; Asorey, Cynthia M; Sandoval, María T; Pérez-Coll, Cristina S; Argibay, Teresa I; Herkovits, Jorge

2009-02-01

The adverse effects of ultraviolet B radiation from 547.2 to 30,096 J/m2 on morphogenesis, cell differentiation, and lethality of amphibian embryos at six developmental stages were evaluated from 24 up to 168 h postexposure. The ultraviolet B radiation lethal dose 10, 50, and 90 values were obtained for all developmental stages evaluated. The lethal dose 50 values, considered as the dose causing lethality in the 50% of the organisms exposed, in J/m2 at 168 h postexposure, ranged from 2,307 to 18,930; gill circulation and blastula were the most susceptible and resistant stages, respectively. Ultraviolet B radiation caused malformations in all developmental stages but was significantly more teratogenic at the gill circulation and complete operculum stages. Moreover, at the gill circulation stage, even the lowest dose (547.2 J/m2) resulted in malformations to 100% of embryos. The most common malformations were persistent yolk plug, bifid spine, reduced body size, delayed development, asymmetry, microcephaly and anencephaly, tail and body flexures toward the irradiated side, agenesia or partial gill development, abnormal pigment distribution, and hypermotility. The stage-dependent susceptibility to ultraviolet B radiation during amphibian embryogenesis could be explained in the framework of evoecotoxicology, considering ontogenic features as biomarkers of environmental signatures of living forms ancestors during the evolutionary process. The stage-dependent susceptibility to ultraviolet B radiation on Rhinella (Bufo) arenarum embryos for both lethal and teratogenic effects could contribute to a better understanding of the role of the increased ultraviolet B radiation on worldwide amphibian populations decline.

A Human Espophageal Epithelial Cell Model for Study of Radiation Induced Cancer and DNA Damage Repair

NASA Technical Reports Server (NTRS)

Huff, Janice L.; Patel, Zarana S.; Hada, Megumi; Cucinotta, Francis A.

2008-01-01

For cancer risk assessment in astronauts and for countermeasure development, it is essential to understand the molecular mechanisms of radiation carcinogenesis and how these mechanisms are influenced by exposure to the types of radiation found in space. We are developing an in vitro model system for the study of radiation-induced initiation and progression of esophageal carcinoma, a type of cancer found to have a significant enhancement in incidence in the survivors of the atomic bomb detonations in Japan. Here we present the results of our preliminary characterization of both normal and hTERT immortalized esophageal epithelial cells grown in 2-dimensional culture. We analyzed DNA repair capacity by measuring the kinetics of formation and loss of - H2AX foci following radiation exposure. Additionally, we analyzed induction of chromosomal aberrations using 3-color fluorescence in situ hybridization (FISH). Data were generated using both low LET (gamma rays) and high LET ions (1000 MeV/nucleon iron).

THE ANTIGENIC POTENCY OF EPIDEMIC INFLUENZA VIRUS FOLLOWING INACTIVATION BY ULTRAVIOLET RADIATION

PubMed Central

Salk, Jonas E.; Lavin, G. I.; Francis, Thomas

1940-01-01

A study of the antigenic potency of influenza virus inactivated by ultraviolet radiation has been made. Virus so inactivated is still capable of functioning as an immunizing agent when given to mice by the intraperitoneal route. In high concentrations inactivated virus appears to be nearly as effective as active virus but when quantitative comparisons of the immunity induced by different dilutions are made, it is seen that a hundredfold loss in immunizing capacity occurs during inactivation. Virus in suspensions prepared from the lungs of infected mice is inactivated more rapidly than virus in tissue culture medium. A standard for the comparison of vaccines of epidemic influenza virus is proposed. PMID:19871057

Space Radiation Effects on Human Cells: Modeling DNA Breakage, DNA Damage Foci Distribution, Chromosomal Aberrations and Tissue Effects

NASA Technical Reports Server (NTRS)

Ponomarev, A. L.; Huff, J. L.; Cucinotta, F. A.

2011-01-01

Future long-tem space travel will face challenges from radiation concerns as the space environment poses health risk to humans in space from radiations with high biological efficiency and adverse post-flight long-term effects. Solar particles events may dramatically affect the crew performance, while Galactic Cosmic Rays will induce a chronic exposure to high-linear-energy-transfer (LET) particles. These types of radiation, not present on the ground level, can increase the probability of a fatal cancer later in astronaut life. No feasible shielding is possible from radiation in space, especially for the heavy ion component, as suggested solutions will require a dramatic increase in the mass of the mission. Our research group focuses on fundamental research and strategic analysis leading to better shielding design and to better understanding of the biological mechanisms of radiation damage. We present our recent effort to model DNA damage and tissue damage using computational models based on the physics of heavy ion radiation, DNA structure and DNA damage and repair in human cells. Our particular area of expertise include the clustered DNA damage from high-LET radiation, the visualization of DSBs (DNA double strand breaks) via DNA damage foci, image analysis and the statistics of the foci for different experimental situations, chromosomal aberration formation through DSB misrepair, the kinetics of DSB repair leading to a model-derived spectrum of chromosomal aberrations, and, finally, the simulation of human tissue and the pattern of apoptotic cell damage. This compendium of theoretical and experimental data sheds light on the complex nature of radiation interacting with human DNA, cells and tissues, which can lead to mutagenesis and carcinogenesis later in human life after the space mission.

Increased exposure of Southern Ocean phytoplankton to ultraviolet radiation

NASA Astrophysics Data System (ADS)

Lubin, Dan; Arrigo, Kevin R.; van Dijken, Gert L.

2004-05-01

Satellite remote sensing of both surface solar ultraviolet radiation (UVR) and chlorophyll over two decades shows that biologically significant ultraviolet radiation increases began to occur over the Southern Ocean three years before the ozone ``hole'' was discovered. Beginning in October 1983, the most frequent occurrences of enhanced UVR over phytoplankton-rich waters occurred in the Weddell Sea and Indian Ocean sectors of the Southern Ocean, impacting 60% of the surface biomass by the late 1990s. These results suggest two reasons why more serious impacts to the base of the marine food web may not have been detected by field experiments: (1) the onset of UVR increases several years before dedicated field work began may have impacted the most sensitive organisms long before such damage could be detected, and (2) most biological field work has so far not taken place in Antarctic waters most extensively subjected to enhanced UVR.

Determination of human DNA polymerase utilization for the repair of a model ionizing radiation-induced DNA strand break lesion in a defined vector substrate

NASA Technical Reports Server (NTRS)

Winters, T. A.; Russell, P. S.; Kohli, M.; Dar, M. E.; Neumann, R. D.; Jorgensen, T. J.

1999-01-01

Human DNA polymerase and DNA ligase utilization for the repair of a major class of ionizing radiation-induced DNA lesion [DNA single-strand breaks containing 3'-phosphoglycolate (3'-PG)] was examined using a novel, chemically defined vector substrate containing a single, site-specific 3'-PG single-strand break lesion. In addition, the major human AP endonuclease, HAP1 (also known as APE1, APEX, Ref-1), was tested to determine if it was involved in initiating repair of 3'-PG-containing single-strand break lesions. DNA polymerase beta was found to be the primary polymerase responsible for nucleotide incorporation at the lesion site following excision of the 3'-PG blocking group. However, DNA polymerase delta/straightepsilon was also capable of nucleotide incorporation at the lesion site following 3'-PG excision. In addition, repair reactions catalyzed by DNA polymerase beta were found to be most effective in the presence of DNA ligase III, while those catalyzed by DNA polymerase delta/straightepsilon appeared to be more effective in the presence of DNA ligase I. Also, it was demonstrated that the repair initiating 3'-PG excision reaction was not dependent upon HAP1 activity, as judged by inhibition of HAP1 with neutralizing HAP1-specific polyclonal antibody.

Biomolecular damage induced by ionizing radiation: the direct and indirect effects of low-energy electrons on DNA.

PubMed

Alizadeh, Elahe; Orlando, Thomas M; Sanche, Léon

2015-04-01

Many experimental and theoretical advances have recently allowed the study of direct and indirect effects of low-energy electrons (LEEs) on DNA damage. In an effort to explain how LEEs damage the human genome, researchers have focused efforts on LEE interactions with bacterial plasmids, DNA bases, sugar analogs, phosphate groups, and longer DNA moieties. Here, we summarize the current understanding of the fundamental mechanisms involved in LEE-induced damage of DNA and complex biomolecule films. Results obtained by several laboratories on films prepared and analyzed by different methods and irradiated with different electron-beam current densities and fluencies are presented. Despite varied conditions (e.g., film thicknesses and morphologies, intrinsic water content, substrate interactions, and extrinsic atmospheric compositions), comparisons show a striking resemblance in the types of damage produced and their yield functions. The potential of controlling this damage using molecular and nanoparticle targets with high LEE yields in targeted radiation-based cancer therapies is also discussed.

Effects of near ultraviolet and green radiations on plant growth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klein, R.M.; Edsall, P.C.; Gentile, A.C.

Selective removal of near ultraviolet and green wavelengths from white light permitted enhanced growth of marigold, tomato, corn, and Impatiens plants, Chlamydomonas cells and the mycelium of Sordaria. Additions of near ultraviolet and green radiations caused repressions in the growth of marigold and Sordaria. These wavelengths do not alter the oxidative mechanisms of mitochondria, intact algal cells or marigold leaf tissues. The capacity for chlorophyll and carotenoid synthesis by Euglena cells was unaffected by these wavelengths. 23 references, 2 figures, 4 tables.

Geant4-DNA simulation of DNA damage caused by direct and indirect radiation effects and comparison with biological data.

NASA Astrophysics Data System (ADS)

Villagrasa, Carmen; Meylan, Sylvain; Gonon, Geraldine; Gruel, Gaëtan; Giesen, Ulrich; Bueno, Marta; Rabus, Hans

2017-09-01

In this work we present results obtained in the frame of the BioQuaRT project. The objective of the study was the correlation between the number of radiation-induced double strand breaks (DSB) of the DNA molecule and the probability of detecting nuclear foci after targeted microbeam irradiation of cells with protons and alpha particles of different LET. The former were obtained by simulation with new methods integrated into Geant4-DNA that permit calculating the number of DSB in a DNA target model induced by direct and indirect radiation effects. A particular focus was laid in this work on evaluating the influence of different criteria applied to the simulated results for predicting the formation of a direct SSB. Indeed, these criteria have an important impact on the predicted number of DSB per particle track and its dependence with LET. Among the criteria tested in this work, the case that a direct radiation interaction leads to a strand break if the cumulative energy deposited in the backbone part of one nucleotide exceeds a threshold of 17.5 eV leads to the best agreement with the relative LET dependence of number of radiation induced foci. Further calculations and experimental data are nevertheless needed in order to fix the simulation parameters and to help interpreting the biological experimental data observed by immunofluorescence in terms of the DSB complexity.

Observed ozone response to variations in solar ultraviolet radiation

NASA Technical Reports Server (NTRS)

Gille, J. C.; Smythe, C. M.; Heath, D. F.

1984-01-01

During the winter of 1979, the solar ultraviolet irradiance varied with a period of 13.5 days and an amplitude of 1 percent. The zonal mean ozone values in the tropics varied with the solar irradiance, with an amplitude of 0.25 to 0.60 percent. This observation agrees with earlier calculations, although the response may be overestimated. These results imply changes in ozone at an altitude of 48 kilometers of up to 12 percent over an 11-year solar cycle. Interpretation of ozone changes in the upper stratosphere will require measurements of solar ultraviolet radiation at wavelengths near 200 nanometers.

ULTRAVIOLET RADIATION DOSE AND AMPHIBIAN DISTRIBUTIONS IN NATIONAL PARKS

EPA Science Inventory

Ultraviolet Radiation Dose and Amphibian Distributions in National Parks. Diamond, S. A., Detenbeck, N. E., USEPA, Duluth, MN, USA, Bradford, D. F., USEPA, Las Vegas, NV, USA, Trenham, P. C., University of California, Davis, CA., USA, Adams, M. J., Corn, P. S., Hossack, B., USGS,...

Sources and measurement of ultraviolet radiation.

PubMed

Diffey, Brian L

2002-09-01

Ultraviolet (UV) radiation is part of the electromagnetic spectrum. The biological effects of UV radiation vary enormously with wavelength and for this reason the UV spectrum is further subdivided into three regions: UVA, UVB, and UVC. Quantities of UV radiation are expressed using radiometric terminology. A particularly important term in clinical photobiology is the standard erythema dose (SED), which is a measure of the erythemal effectiveness of a UV exposure. UV radiation is produced either by heating a body to an incandescent temperature, as is the case with solar UV, or by passing an electric current through a gas, usually vaporized mercury. The latter process is the mechanism whereby UV radiation is produced artificially. Both the quality (spectrum) and quantity (intensity) of terrestrial UV radiation vary with factors including the elevation of the sun above the horizon and absorption and scattering by molecules in the atmosphere, notably ozone, and by clouds. For many experimental studies in photobiology it is simply not practicable to use natural sunlight and so artificial sources of UV radiation designed to simulate the UV component of sunlight are employed; these are based on either optically filtered xenon arc lamps or fluorescent lamps. The complete way to characterize an UV source is by spectroradiometry, although for most practical purposes a detector optically filtered to respond to a limited portion of the UV spectrum normally suffices.

The Effect of a Grape Seed Extract on Radiation-Induced DNA Damage in Human Lymphocytes

NASA Astrophysics Data System (ADS)

Dicu, Tiberius; Postescu, Ion D.; Foriş, Vasile; Brie, Ioana; Fischer-Fodor, Eva; Cernea, Valentin; Moldovan, Mircea; Cosma, Constantin

2009-05-01

Plant-derived antioxidants due to their phenolic compounds content are reported as potential candidates for reducing the levels of oxidative stress in living organisms. Grape seed extracts are very potent antioxidants and exhibit numerous interesting pharmacologic activities. Hydroethanolic (50/50, v/v) standardized extract was obtained from red grape seed (Vitis vinifera, variety Burgund Mare—BM). The total polyphenols content was evaluated by Folin-Ciocalteu procedure and expressed as μEq Gallic Acid/ml. The aim of this study was to evaluate the potential antioxidant effects of different concentrations of BM extract against 60Co γ-rays induced DNA damage in human lymphocytes. Samples of human lymphocytes were incubated with BM extract (12.5, 25.0 and 37.5 μEq GA/ml, respectively) administered at 30 minutes before in vitro irradiation with γ-rays (2 Gy). The DNA damage and repair in lymphocytes were evaluated using alkaline comet assay. Using the lesion score, the radiation-induced DNA damage was found to be significantly different (p<0.05) from control, both in the absence and presence of BM extract (except the lymphocytes treated with 37.5 μEq GA/ml BM extract). DNA repair analyzed by incubating the irradiated cells at 37° C and 5% CO2 atmosphere for 2 h, indicated a significant difference (p<0.05) in the lymphocytes group treated with 25.0 μEq GA/ml BM extract, immediately and two hours after irradiation. These results suggest radioprotective effects after treatment with BM extract in human lymphocytes.

Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms.

PubMed

Nichols, Joi A; Katiyar, Santosh K

2010-03-01

Epidemiological, clinical and laboratory studies have implicated solar ultraviolet (UV) radiation in various skin diseases including, premature aging of the skin and melanoma and non-melanoma skin cancers. Chronic UV radiation exposure-induced skin diseases or skin disorders are caused by the excessive induction of inflammation, oxidative stress and DNA damage, etc. The use of chemopreventive agents, such as plant polyphenols, to inhibit these events in UV-exposed skin is gaining attention. Chemoprevention refers to the use of agents that can inhibit, reverse or retard the process of these harmful events in the UV-exposed skin. A wide variety of polyphenols or phytochemicals, most of which are dietary supplements, have been reported to possess substantial skin photoprotective effects. This review article summarizes the photoprotective effects of some selected polyphenols, such as green tea polyphenols, grape seed proanthocyanidins, resveratrol, silymarin and genistein, on UV-induced skin inflammation, oxidative stress and DNA damage, etc., with a focus on mechanisms underlying the photoprotective effects of these polyphenols. The laboratory studies conducted in animal models suggest that these polyphenols have the ability to protect the skin from the adverse effects of UV radiation, including the risk of skin cancers. It is suggested that polyphenols may favorably supplement sunscreens protection, and may be useful for skin diseases associated with solar UV radiation-induced inflammation, oxidative stress and DNA damage.

Regulatory effect of Bcl-2 in ultraviolet radiation-induced apoptosis of the mouse crystalline lens

PubMed Central

DONG, YUCHEN; ZHENG, YAJUAN; XIAO, JUN; ZHU, CHAO; ZHAO, MEISHENG

2016-01-01

The aim of the present study was to analyze the role of Bcl-2 during the process of apoptosis in the mouse crystalline lens. In total, 12 normal mice served as the control group and 12 Bcl-2 knockout (K.O) mice served as the experimental group. The mouse crystalline lens was sampled for the detection of Bcl-2 and caspase-3 expression following exposure to ultraviolet (UV) radiation. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine Bcl-2 expression in the groups of normal mice receiving UV radiation or not receiving UV radiation. Samples of the murine crystalline lens were microscopically harvested and analyzed using western blotting. Apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Furthermore, caspase 3 activity was examined using enzyme-linked immunosorbent assay kits, and RT-qPCR was used to analyze caspase-3 expression levels. The results of the present study demonstrated that there was no statistically significant difference in the level of Bcl-2 gene transcription between the two groups. In addition, UV radiation did not change the macrostructure of the crystalline lens in the group of normal mice or the group of Bcl-2 K.O mice. The results of the TUNEL assay indicated that the normal-UV group exhibited a more significant apoptosis level compared with the Bcl-2 K.O-UV group. Furthermore, the mRNA expression level of caspase-3 in the normal-UV group was significantly higher compared with the normal-nonUV group (P<0.05), while the levels in the Bcl-2 K.O-UV group were significantly higher compared with the Bcl-2 K.O and normal-nonUV groups (P<0.05). In addition, the mRNA expression level of caspase-3 was significantly higher in the normal-UV, as compared with the Bcl-2 K.O-UV group (P<0.05), and the variation trends in caspase-3 activity were consistent. In conclusion, the results of the present study demonstrated that Bcl-2 may have an important role in the

Regulatory effect of Bcl-2 in ultraviolet radiation-induced apoptosis of the mouse crystalline lens.

PubMed

Dong, Yuchen; Zheng, Yajuan; Xiao, Jun; Zhu, Chao; Zhao, Meisheng

2016-03-01

The aim of the present study was to analyze the role of Bcl-2 during the process of apoptosis in the mouse crystalline lens. In total, 12 normal mice served as the control group and 12 Bcl-2 knockout (K.O) mice served as the experimental group. The mouse crystalline lens was sampled for the detection of Bcl-2 and caspase-3 expression following exposure to ultraviolet (UV) radiation. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine Bcl-2 expression in the groups of normal mice receiving UV radiation or not receiving UV radiation. Samples of the murine crystalline lens were microscopically harvested and analyzed using western blotting. Apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Furthermore, caspase 3 activity was examined using enzyme-linked immunosorbent assay kits, and RT-qPCR was used to analyze caspase-3 expression levels. The results of the present study demonstrated that there was no statistically significant difference in the level of Bcl-2 gene transcription between the two groups. In addition, UV radiation did not change the macrostructure of the crystalline lens in the group of normal mice or the group of Bcl-2 K.O mice. The results of the TUNEL assay indicated that the normal-UV group exhibited a more significant apoptosis level compared with the Bcl-2 K.O-UV group. Furthermore, the mRNA expression level of caspase-3 in the normal-UV group was significantly higher compared with the normal-nonUV group (P<0.05), while the levels in the Bcl-2 K.O-UV group were significantly higher compared with the Bcl-2 K.O and normal-nonUV groups (P<0.05). In addition, the mRNA expression level of caspase-3 was significantly higher in the normal-UV, as compared with the Bcl-2 K.O-UV group (P<0.05), and the variation trends in caspase-3 activity were consistent. In conclusion, the results of the present study demonstrated that Bcl-2 may have an important role in the

Ultraviolet-B Protective Effect of Flavonoids from Eugenia caryophylata on Human Dermal Fibroblast Cells.

PubMed

Patwardhan, Juilee; Bhatt, Purvi

2015-10-01

The exposure of skin to ultraviolet-B (UV-B) radiations leads to deoxyribonucleic acid (DNA) damage and can induce production of free radicals which imbalance the redox status of the cell and lead to increased oxidative stress. Clove has been traditionally used for its analgesic, anti-inflammatory, anti-microbial, anti-viral, and antiseptic effects. To evaluate the UV-B protective activity of flavonoids from Eugenia caryophylata (clove) buds on human dermal fibroblast cells. Protective ability of flavonoid-enriched (FE) fraction of clove was studied against UV-B induced cytotoxicity, anti-oxidant regulation, oxidative DNA damage, intracellular reactive oxygen species (ROS) generation, apoptotic morphological changes, and regulation of heme oxygenase-1 (HO-1) gene through nuclear factor E2-related factor 2 antioxidant response element (Nrf2 ARE) pathway. FE fraction showed a significant antioxidant potential. Pretreatment of cells with FE fraction (10-40 μg/ml) reversed the effects of UV-B induced cytotoxicity, depletion of endogenous enzymatic antioxidants, oxidative DNA damage, intracellular ROS production, apoptotic changes, and overexpression of Nrf2 and HO-1. The present study demonstrated for the first time that the FE fraction from clove could confer UV-B protection probably through the Nrf2-ARE pathway, which included the down-regulation of Nrf2 and HO-1. These findings suggested that the flavonoids from clove could potentially be considered as UV-B protectants and can be explored further for its topical application to the area of the skin requiring protection. Pretreatment of human dermal fibroblast with flavonoid-enriched fraction of Eugenia caryophylata attenuated effects of ultraviolet-B radiationsIt also conferred protection through nuclear factor E2-related factor 2-antioxidant response pathway and increased tolerance of cells against oxidative stressFlavonoid-enriched fraction can be explored further for topical application to the skin as a

A human esophageal epithelial cell model for study of radiation induced cancer and DNA repair

NASA Astrophysics Data System (ADS)

Huff, Janice; Patel, Zarana; Hada, Megumi; Cucinotta, Francis A.

For cancer risk assessment in astronauts and for countermeasure development, it is essential to understand the molecular mechanisms of radiation carcinogenesis and how these mechanisms are influenced by exposure to the types of radiation found in space. We are developing an in vitro model system for the study of radiation-induced initiation and progression of esophageal carcinoma. Development of squamous cell carcinoma of the esophagus is associated with radiation exposure, as revealed by the significant enhanced in incidence rates for this type of cancer in the survivors of the atomic bomb detonations in Japan. It is also associated with poor nutritional status and micronutrient deficiencies, which are also important issues for long duration spaceflight. The possible synergies between nutritional issues and radiation exposure are unknown. Here we present the results of preliminary characterization of both normal and hTERT-immortalized esophageal epithelial cells grown in 2-dimensional culture. We analyzed DNA repair capacity by measuring the kinetics of formation and loss of gamma-H2AX foci following radiation exposure. Additionally, we analyzed induction of chromosomal aberrations using 3-color fluorescence in situ hybridization (FISH). Data were generated using both low LET (gamma rays) and high LET ions (1000 MeV/nucleon iron.

Low temperature plasmas induced in SF6 by extreme ultraviolet (EUV) pulses

NASA Astrophysics Data System (ADS)

Bartnik, A.; Skrzeczanowski, W.; Czwartos, J.; Kostecki, J.; Fiedorowicz, H.; Wachulak, P.; Fok, T.

2018-06-01

In this work, a comparative study of extreme ultraviolet (EUV) induced low temperature SF6-based plasmas, created using two different irradiation systems, was performed. Both systems utilized laser-produced plasma (LPP) EUV sources. The essential difference between the systems concerned the formation of the driving EUV beam. The first one contained an efficient ellipsoidal EUV collector allowing for focusing of the EUV radiation at a large distance from the LPP source. The spectrum of focused radiation was limited to the long-wavelength part of the total LPP emission, λ > 8 nm, due to the reflective properties of the collector. The second system did not contain any EUV collector. The gas to be ionized was injected in the vicinity of the LPP, at a distance of the order of 10 mm. In both systems, energies of the driving photons were high enough for dissociative ionization of the SF6 molecules and ionization of atoms or even singly charged ions. Plasmas, created due to these processes, were investigated by spectral measurements in the EUV, ultraviolet (UV), and visible (VIS) spectral ranges. These low temperature plasmas were employed for preliminary experiments concerning surface treatment. The formation of pronounced nanostructures on the silicon surface after plasma treatment was demonstrated.

DNA damage induced by boron neutron capture therapy is partially repaired by DNA ligase IV.

PubMed

Kondo, Natsuko; Sakurai, Yoshinori; Hirota, Yuki; Tanaka, Hiroki; Watanabe, Tsubasa; Nakagawa, Yosuke; Narabayashi, Masaru; Kinashi, Yuko; Miyatake, Shin-ichi; Hasegawa, Masatoshi; Suzuki, Minoru; Masunaga, Shin-ichiro; Ohnishi, Takeo; Ono, Koji

2016-03-01

Boron neutron capture therapy (BNCT) is a particle radiation therapy that involves the use of a thermal or epithermal neutron beam in combination with a boron ((10)B)-containing compound that specifically accumulates in tumor. (10)B captures neutrons and the resultant fission reaction produces an alpha ((4)He) particle and a recoiled lithium nucleus ((7)Li). These particles have the characteristics of high linear energy transfer (LET) radiation and therefore have marked biological effects. High-LET radiation is a potent inducer of DNA damage, specifically of DNA double-strand breaks (DSBs). The aim of the present study was to clarify the role of DNA ligase IV, a key player in the non-homologous end-joining repair pathway, in the repair of BNCT-induced DSBs. We analyzed the cellular sensitivity of the mouse embryonic fibroblast cell lines Lig4-/- p53-/- and Lig4+/+ p53-/- to irradiation using a thermal neutron beam in the presence or absence of (10)B-para-boronophenylalanine (BPA). The Lig4-/- p53-/- cell line had a higher sensitivity than the Lig4+/+ p53-/-cell line to irradiation with the beam alone or the beam in combination with BPA. In BNCT (with BPA), both cell lines exhibited a reduction of the 50 % survival dose (D 50) by a factor of 1.4 compared with gamma-ray and neutron mixed beam (without BPA). Although it was found that (10)B uptake was higher in the Lig4+/+ p53-/- than in the Lig4-/- p53-/- cell line, the latter showed higher sensitivity than the former, even when compared at an equivalent (10)B concentration. These results indicate that BNCT-induced DNA damage is partially repaired using DNA ligase IV.

DNA Excision Repair at Telomeres

PubMed Central

Jia, Pingping; Her, Chengtao; Chai, Weihang

2015-01-01

DNA damage is caused by either endogenous cellular metabolic processes such as hydrolysis, oxidation, alkylation, and DNA base mismatches, or exogenous sources including ultraviolet (UV) light, ionizing radiation, and chemical agents. Damaged DNA that is not properly repaired can lead to genomic instability, driving tumorigenesis. To protect genomic stability, mammalian cells have evolved highly conserved DNA repair mechanisms to remove and repair DNA lesions. Telomeres are composed of long tandem TTAGGG repeats located at the ends of chromosomes. Maintenance of functional telomeres is critical for preventing genome instability. The telomeric sequence possesses unique features that predispose telomeres to a variety of DNA damage induced by environmental genotoxins. This review briefly describes the relevance of excision repair pathways in telomere maintenance, with the focus on base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR). By summarizing current knowledge on excision repair of telomere damage and outlining many unanswered questions, it is our hope to stimulate further interest in a better understanding of excision repair processes at telomeres and in how these processes contribute to telomere maintenance. PMID:26422132

Ultraviolet Radiation: Cellular Antioxidant Response and the Role of Ocular Aldehyde Dehydrogenase Enzymes

PubMed Central

Marchitti, Satori A.; Chen, Ying; Thompson, David C.; Vasiliou, Vasilis

2011-01-01

Solar ultraviolet radiation (UVR) exposes the human eye to near constant oxidative stress. Evidence suggests that UVR is the most important environmental insult leading to the development of a variety of ophthalmoheliosis disorders. UVR-induced reactive oxygen species are highly reactive with DNA, proteins and cellular membranes, resulting in cellular and tissue damage. Antioxidant defense systems present in ocular tissues function to combat reactive oxygen species and protect the eye from oxidative damage. Important enzymatic antioxidants are the superoxide dismutases, catalase, glutathione peroxidases, glutathione reductase and members of the aldehyde dehydrogenase (ALDH) superfamily. Glutathione, ascorbic and uric acids, α-tocopherol, NADPH and ferritin serve as small molecule, nonenzymatic antioxidants. Ocular tissues have high levels of these antioxidants which are essential for the maintenance of redox homeostasis in the eye and protection against oxidative damage. ALDH1A1 and ALDH3A1, present abundantly in the cornea and lens, have been shown to have unique roles in the defense against UVR and the downstream effects of oxidative stress. This review presents the properties and functions of ocular antioxidants that play critical roles in the cellular response to UVR exposure, including a focused discussion of the unique roles that the ALDH1A1 and ALDH3A1 enzymes have as multi-functional ocular antioxidants. PMID:21670692

Ultraviolet Radiation in Wound Care: Sterilization and Stimulation

PubMed Central

Gupta, Asheesh; Avci, Pinar; Dai, Tianhong; Huang, Ying-Ying; Hamblin, Michael R.

2013-01-01

Significance Wound care is an important area of medicine considering the increasing age of the population who may have diverse comorbidities. Light-based technology comprises a varied set of modalities of increasing relevance to wound care. While low-level laser (or light) therapy and photodynamic therapy both have wide applications in wound care, this review will concentrate on the use of ultraviolet (UV) radiation. Recent Advances UVC (200–280 nm) is highly antimicrobial and can be directly applied to acute wound infections to kill pathogens without unacceptable damage to host tissue. UVC is already widely applied for sterilization of inanimate objects. UVB (280–315 nm) has been directly applied to the wounded tissue to stimulate wound healing, and has been widely used as extracorporeal UV radiation of blood to stimulate the immune system. UVA (315–400 nm) has distinct effects on cell signaling, but has not yet been widely applied to wound care. Critical Issues Penetration of UV light into tissue is limited and optical technology may be employed to extend this limit. UVC and UVB can damage DNA in host cells and this risk must be balanced against beneficial effects. Chronic exposure to UV can be carcinogenic and this must be considered in planning treatments. Future Directions New high-technology UV sources, such as light-emitting diodes, lasers, and microwave-generated UV plasma are becoming available for biomedical applications. Further study of cellular signaling that occurs after UV exposure of tissue will allow the benefits in wound healing to be better defined. PMID:24527357

The influence of UV radiation on protistan evolution

NASA Technical Reports Server (NTRS)

Rothschild, L. J.

1999-01-01

Ultraviolet radiation has provided an evolutionary challenge to life on Earth. Recent increases in surficial ultraviolet B fluxes have focused attention on the role of UV radiation in protistan ecology, cancer, and DNA damage. Exploiting this new wealth of data, I examine the possibility that ultraviolet radiation may have played a significant role in the evolution of the first eukaryotes, that is, protists. Protists probably arose well before the formation of a significant ozone shield, and thus were probably subjected to substantial ultraviolet A, ultraviolet B, and ultraviolet C fluxes early in their evolution. Evolution consists of the generation of heritable variations and the subsequent selection of these variants. Ultraviolet radiation has played a role both as a mutagen and as a selective agent. In its role as a mutagen, it may have been crucial in the origin of sex and as a driver of molecular evolution. As a selective agent, its influence has been broad. Discussed in this paper are the influence of ultraviolet radiation on biogeography, photosynthesis, and desiccation resistance.

Solar Activity, Ultraviolet Radiation and Consequences in Birds in Mexico City, 2001- 2002

NASA Astrophysics Data System (ADS)

Valdes, M.; Velasco, V.

2008-12-01

Anomalous behavior in commercial and pet birds in Mexico City was reported during 2002 by veterinarians at the Universidad Nacional Autonoma de Mexico. This was attributed to variations in the surrounding luminosity. The solar components, direct, diffuse, global, ultraviolet band A and B, as well as some meteorological parameters, temperature, relative humidity, and precipitation, were then analyzed at the Solar Radiation Laboratory. Although the total annual radiance of the previously mentioned radiation components did not show important changes, ultraviolet Band-B solar radiation did vary significantly. During 2001 the total annual irradiance , 61.05 Hjcm² to 58.32 Hjcm², was 1.6 standard deviations lower than one year later, in 2002 and increased above the mean total annual irradiance, to 65.75 Hjcm², 2.04 standard deviations, giving a total of 3.73 standard deviations for 2001-2002. Since these differences did not show up clearly in the other solar radiation components, daily extra-atmosphere irradiance was analyzed and used to calculate the total annual extra-atmosphere irradiance, which showed a descent for 2001. Our conclusions imply that Ultraviolet Band-B solar radiation is representative of solar activity and has an important impact on commercial activity related with birds.

Ultraviolet-B radiation induced cross-linking improves physical properties of cold- and warm-water fish gelatin gels and films.

PubMed

Otoni, Caio G; Avena-Bustillos, Roberto J; Chiou, Bor-Sen; Bilbao-Sainz, Cristina; Bechtel, Peter J; McHugh, Tara H

2012-09-01

Cold- and warm-water fish gelatin granules were exposed to ultraviolet-B radiation for doses up to 29.7 J/cm(2). Solutions and films were prepared from the granules. Gel electrophoresis and refractive index were used to examine changes in molecular weight of the samples. Also, the gel strength and rheological properties of the solutions as well as the tensile and water vapor barrier properties of the films were characterized. SDS-PAGE and refractive index results indicated cross-linking of gelatin chains after exposure to radiation. Interestingly, UV-B treated samples displayed higher gel strengths, with cold- and warm-water fish gelatin having gel strength increases from 1.39 to 2.11 N and from 7.15 to 8.34 N, respectively. In addition, both gelatin samples exhibited an increase in viscosity for higher UV doses. For gelatin films, the cold-water fish gelatin samples made from irradiated granules showed greater tensile strength. In comparison, the warm-water gelatin films made from irradiated granules had lower tensile strength, but better water vapor barrier properties. This might be due to the UV induced cross-linking in warm-water gelatin that disrupted helical structures. Journal of Food Science copy; 2012 Institute of Food Technologists® No claim to original US government works.

Chondracanthus tenellus (Harvey) hommersand extract protects the human keratinocyte cell line by blocking free radicals and UVB radiation-induced cell damage.

PubMed

Piao, Mei Jing; Hyun, Yu Jae; Oh, Tae-Heon; Kang, Hee Kyoung; Yoo, Eun Sook; Koh, Young Sang; Lee, Nam Ho; Suh, In Soo; Hyun, Jin Won

2012-12-01

The aim of this study was to investigate the protective effects of the ethanol extract of the red algae Chondracanthus tenellus (Harvey) Hommersand (CTE) on cultured human keratinocyte cell line. The cellular protection conferred by CTE was evidenced by the ability of the extract to absorb ultraviolet B (UVB; 280-320 nm) and to scavenge the radical 1,1-diphenyl-2-picrylhydrazyl, as well as intracellular reactive oxygen species (ROS), induced by either hydrogen peroxide (H(2)O(2)) or UVB radiation. In addition, both superoxide anion generated by the xanthine/xanthine oxidase system and hydroxyl radical generated by the Fenton reaction (FeSO(4) + H(2)O(2)) were scavenged by CTE, as confirmed using electron spin resonance spectrometry. In the human keratinocyte cell line, CTE decreased the degree of injury resulting from UVB-induced oxidative stress to lipids, proteins, and DNA. CTE-treated cells also showed a reduction in UVB-induced apoptosis, as exemplified by fewer apoptotic bodies and less DNA fragmentation. Taken together, these results suggest that CTE confers protection on the human keratinocyte cell line against UVB-induced oxidative stress by absorbing UVB ray and scavenging ROS, thereby reducing injury to cellular constituents.

DNA-dependent protein kinase is a molecular target for the development of noncytotoxic radiation-sensitizing drugs.

PubMed

Shinohara, Eric T; Geng, Ling; Tan, Jiahui; Chen, Heidi; Shir, Yu; Edwards, Eric; Halbrook, James; Kesicki, Edward A; Kashishian, Adam; Hallahan, Dennis E

2005-06-15

DNA-dependent protein kinase (DNA-PK)-defective severe combined immunodeficient (SCID) mice have a greater sensitivity to ionizing radiation compared with wild-type mice due to deficient repair of DNA double-strand break. SCID cells were therefore studied to determine whether radiosensitization by the specific inhibitor of DNA-PK, IC87361, is eliminated in the absence of functional DNA-PK. IC87361 enhanced radiation sensitivity in wild-type C57BL6 endothelial cells but not in SCID cells. The tumor vascular window model was used to assess IC87361-induced radiosensitization of SCID and wild-type tumor microvasculature. Vascular density was 5% in irradiated SCID host compared with 50% in C57BL6 mice (P < 0.05). IC87361 induced radiosensitization of tumor microvasculature in wild-type mice that resembled the radiosensitive phenotype of tumor vessels in SCID mice. Radiosensitization by IC87361 was eliminated in SCID tumor vasculature, which lack functional DNA-PK. Irradiated LLC and B16F0 tumors implanted into SCID mice showed greater tumor growth delay compared with tumors implanted into either wild-type C57BL6 or nude mice. Furthermore, LLC tumors treated with radiation and IC87361 showed tumor growth delay that was significantly greater than tumors treated with radiation alone (P < 0.01 for 3 Gy alone versus 3 Gy + IC87361). DNA-PK inhibitors induced no cytotoxicity and no toxicity in mouse normal tissues. Mouse models deficient in enzyme activity are useful to assess the specificity of novel kinase inhibitors. DNA-PK is an important target for the development of novel radiation-sensitizing drugs that have little intrinsic cytotoxicity.

UV-B Radiation Induces Root Bending Through the Flavonoid-Mediated Auxin Pathway in Arabidopsis.

PubMed

Wan, Jinpeng; Zhang, Ping; Wang, Ruling; Sun, Liangliang; Wang, Wenying; Zhou, Huakun; Xu, Jin

2018-01-01

Ultraviolet (UV)-B radiation-induced root bending has been reported; however, the underlying mechanisms largely remain unclear. Here, we investigate whether and how auxin and flavonoids are involved in UV-B radiation-induced root bending in Arabidopsis using physiological, pharmacological, and genetic approaches. UV-B radiation modulated the direction of root growth by decreasing IAA biosynthesis and affecting auxin distribution in the root tips, where reduced auxin accumulation and asymmetric auxin distribution were observed. UV-B radiation increased the distribution of auxin on the nonradiated side of the root tips, promoting growth and causing root bending. Further analysis indicated that UV-B induced an asymmetric accumulation of flavonoids; this pathway is involved in modulating the accumulation and asymmetric distribution of auxin in root tips and the subsequent redirection of root growth by altering the distribution of auxin carriers in response to UV-B radiation. Taken together, our results indicate that UV-B radiation-induced root bending occurred through a flavonoid-mediated phototropic response to UV-B radiation.

DNA double strand breaks induced by the indirect effect of radiation are more efficiently repaired by non-homologous end joining compared to homologous recombination repair.

PubMed

Bajinskis, Ainars; Natarajan, Adayapalam T; Erixon, Klaus; Harms-Ringdahl, Mats

2013-08-30

The aim of this study was to investigate the relative involvement of three major DNA repair pathways, i.e., non-homologous end joining (NHEJ), homologous recombination (HRR) and base excision (BER) in repair of DNA lesions of different complexity induced by low- or high-LET radiation with emphasis on the contribution of the indirect effect of radiation for these radiation qualities. A panel of DNA repair-deficient CHO cell lines was irradiated by (137)Cs γ-rays or radon progeny α-particles. Irradiation was also performed in the presence of 2M DMSO to reduce the indirect effect of radiation and the complexity of the DNA damage formed. Clonogenic survival and micronucleus assays were used to estimate efficiencies of the different repair pathways for DNA damages produced by direct and indirect effects. Removal of the indirect effect of low-LET radiation by DMSO increased clonogenic survival and decreased MN formation for all cell lines investigated. A direct contribution of the indirect effect of radiation to DNA base damage was suggested by the significant protection by DMSO seen for the BER deficient cell line. Lesions formed by the indirect effect are more readily repaired by the NHEJ pathway than by HRR after irradiation with γ-rays or α-particles as evaluated by cell survival and the yields of MN. The results obtained with BER- and NHEJ-deficient cells suggest that the indirect effect of radiation contributes significantly to the formation of repair substrates for these pathways. Copyright © 2013 Elsevier B.V. All rights reserved.

Ultraviolet absorption hygrometer

DOEpatents

Gersh, M.E.; Bien, F.; Bernstein, L.S.

1986-12-09

An ultraviolet absorption hygrometer is provided including a source of pulsed ultraviolet radiation for providing radiation in a first wavelength region where water absorbs significantly and in a second proximate wavelength region where water absorbs weakly. Ultraviolet radiation in the first and second regions which has been transmitted through a sample path of atmosphere is detected. The intensity of the radiation transmitted in each of the first and second regions is compared and from this comparison the amount of water in the sample path is determined. 5 figs.

Interventions to prevent skin cancer by reducing exposure to ultraviolet radiation: a systematic review.

PubMed

Saraiya, Mona; Glanz, Karen; Briss, Peter A; Nichols, Phyllis; White, Cornelia; Das, Debjani; Smith, S Jay; Tannor, Bernice; Hutchinson, Angela B; Wilson, Katherine M; Gandhi, Nisha; Lee, Nancy C; Rimer, Barbara; Coates, Ralph C; Kerner, Jon F; Hiatt, Robert A; Buffler, Patricia; Rochester, Phyllis

2004-12-01

The relationship between skin cancer and ultraviolet radiation is well established. Behaviors such as seeking shade, avoiding sun exposure during peak hours of radiation, wearing protective clothing, or some combination of these behaviors can provide protection. Sunscreen use alone is not considered an adequate protection against ultraviolet radiation. This report presents the results of systematic reviews of effectiveness, applicability, other harms or benefits, economic evaluations, and barriers to use of selected interventions to prevent skin cancer by reducing exposure to ultraviolet radiation. The Task Force on Community Preventive Services found that education and policy approaches to increasing sun-protective behaviors were effective when implemented in primary schools and in recreational or tourism settings, but found insufficient evidence to determine effectiveness when implemented in other settings, such as child care centers, secondary schools and colleges, and occupational settings. They also found insufficient evidence to determine the effectiveness of interventions oriented to healthcare settings and providers, media campaigns alone, interventions oriented to parents or caregivers of children, and community-wide multicomponent interventions. The report also provides suggestions for areas for future research.

DNA Repair in Human Pluripotent Stem Cells Is Distinct from That in Non-Pluripotent Human Cells

PubMed Central

Luo, Li Z.; Park, Sang-Won; Bates, Steven E.; Zeng, Xianmin; Iverson, Linda E.; O'Connor, Timothy R.

2012-01-01

The potential for human disease treatment using human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells (iPSCs), also carries the risk of added genomic instability. Genomic instability is most often linked to DNA repair deficiencies, which indicates that screening/characterization of possible repair deficiencies in pluripotent human stem cells should be a necessary step prior to their clinical and research use. In this study, a comparison of DNA repair pathways in pluripotent cells, as compared to those in non-pluripotent cells, demonstrated that DNA repair capacities of pluripotent cell lines were more heterogeneous than those of differentiated lines examined and were generally greater. Although pluripotent cells had high DNA repair capacities for nucleotide excision repair, we show that ultraviolet radiation at low fluxes induced an apoptotic response in these cells, while differentiated cells lacked response to this stimulus, and note that pluripotent cells had a similar apoptotic response to alkylating agent damage. This sensitivity of pluripotent cells to damage is notable since viable pluripotent cells exhibit less ultraviolet light-induced DNA damage than do differentiated cells that receive the same flux. In addition, the importance of screening pluripotent cells for DNA repair defects was highlighted by an iPSC line that demonstrated a normal spectral karyotype, but showed both microsatellite instability and reduced DNA repair capacities in three out of four DNA repair pathways examined. Together, these results demonstrate a need to evaluate DNA repair capacities in pluripotent cell lines, in order to characterize their genomic stability, prior to their pre-clinical and clinical use. PMID:22412831

Disinfection of Airborne Organisms by Ultraviolet-C Radiation and Sunlight

DTIC Science & Technology

2012-07-01

organisms deposited on surfaces, suspended in water , and contaminating food, all of which have been discussed elsewhere (Block, 2001). In contrast, the... water . Therefore, the primary means for organism inactivation in aerosols is ultraviolet (UV) radiation. Radiation from the sunlight is used as a...cortex is essential for reduction of the water content in the spore core and formation of a dormant spore. The cortex is degraded in spore

Ultraviolet radiation cataract: dose dependence

NASA Astrophysics Data System (ADS)

Soderberg, Per G.; Loefgren, Stefan

1994-07-01

Current safety limits for cataract development after acute exposure to ultraviolet radiation (UVR) are based on experiments analyzing experimental data with a quantal, effect-no effect, dose-response model. The present study showed that intensity of forward light scattering is better described with a continuous dose-response model. It was found that 3, 30 and 300 kJ/m2UVR300nm induces increased light scattering within 6 h. For all three doses the intensity of forward light scattering was constant after 6 h. The intensity of forward light scattering was proportional to the log dose of UVR300nm. There was a slight increase of the intensity of forward light scattering on the contralateral side in animals that received 300 kJ/m2. Altogether 72 Sprague-Dawley male rats were included. Half of the rats were exposed in vivo on one side to UVR300nm. The other half was kept as a control group, receiving the same treatment as exposed rats but without delivery of UVR300nm to the eye. Subgroups of the rats received either of the three doses. Rats were sacrificed at varying intervals after the exposure. The lenses were extracted and the forward light scattering was estimated. It is concluded that intensity of forward light scattering in the lens after exposure to UVR300nm should be described with a continuous dose-reponse model.

Non-random distribution of DNA double-strand breaks induced by particle irradiation

NASA Technical Reports Server (NTRS)

Lobrich, M.; Cooper, P. K.; Rydberg, B.; Chatterjee, A. (Principal Investigator)

1996-01-01

Induction of DNA double-strand breaks (dsbs) in mammalian cells is dependent on the spatial distribution of energy deposition from the ionizing radiation. For high LET particle radiations the primary ionization sites occur in a correlated manner along the track of the particles, while for X-rays these sites are much more randomly distributed throughout the volume of the cell. It can therefore be expected that the distribution of dsbs linearly along the DNA molecule also varies with the type of radiation and the ionization density. Using pulsed-field gel and conventional gel techniques, we measured the size distribution of DNA molecules from irradiated human fibroblasts in the total range of 0.1 kbp-10 Mbp for X-rays and high LET particles (N ions, 97 keV/microns and Fe ions, 150 keV/microns). On a mega base pair scale we applied conventional pulsed-field gel electrophoresis techniques such as measurement of the fraction of DNA released from the well (FAR) and measurement of breakage within a specific NotI restriction fragment (hybridization assay). The induction rate for widely spaced breaks was found to decrease with LET. However, when the entire distribution of radiation-induced fragments was analysed, we detected an excess of fragments with sizes below about 200 kbp for the particles compared with X-irradiation. X-rays are thus more effective than high LET radiations in producing large DNA fragments but less effective in the production of smaller fragments. We determined the total induction rate of dsbs for the three radiations based on a quantitative analysis of all the measured radiation-induced fragments and found that the high LET particles were more efficient than X-rays at inducing dsbs, indicating an increasing total efficiency with LET. Conventional assays that are based only on the measurement of large fragments are therefore misleading when determining total dsb induction rates of high LET particles. The possible biological significance of this non

Protective effect of 3,4-dihydroxybenzoic acid isolated from Cladophora wrightiana Harvey against ultraviolet B radiation-induced cell damage in human HaCaT keratinocytes.

PubMed

Cha, Ji Won; Piao, Mei Jing; Kim, Ki Cheon; Zheng, Jian; Yao, Cheng Wen; Hyun, Chang Lim; Kang, Hee Kyoung; Yoo, Eun Sook; Koh, Young Sang; Lee, Nam Ho; Ko, Mi Hee; Hyun, Jin Won

2014-03-01

The aim of the present study was to elucidate the protective properties of 3,4-dihydroxybenzoic acid (DBA) isolated from Cladophora wrightiana Harvey (a green alga) against ultraviolet B (UVB)-induced damage to human HaCaT keratinocytes. DBA exhibited scavenging actions against the 1,1-diphenyl-2-picrylhydrazyl radical, the superoxide anion, and the hydroxyl radical. Furthermore, DBA decreased the levels of intracellular reactive oxygen species generated by hydrogen peroxide or UVB treatment of the cells. DBA also decreased the UVB-augmented levels of phospho-histone H2A.X and the extent of comet tail formation, which are both indications of DNA damage. In addition, the compound safeguarded keratinocytes from UVB-induced injury by reversing the production of apoptotic bodies, overturning the disruption of mitochondrial membrane potential, increasing the expression of the anti-apoptotic protein, B-cell lymphoma 2, and decreasing the expression of the pro-apoptotic proteins, Bcl-2-associated X and cleaved caspase-3. Taken together, these results demonstrate that DBA isolated from a green alga protects human keratinocytes against UVB-induced oxidative stress and apoptosis.

Research in extreme ultraviolet and far ultraviolet astronomy

NASA Technical Reports Server (NTRS)

Labov, S. E.

1985-01-01

Instruments designed to explore different aspects of far and extreme ultraviolet cosmic radiation were studied. The far ultraviolet imager (FUVI) was flown on the Aries sounding rocket. Its unique large format 75mm detector mapped out the far ultraviolet background radiation with a resolution of only a few arc minutes. Analysis of this data indicates to what extent the FUVI background is extra galactic in origin. A power spectrum of the spatial fluctuations will have direct consequences for galactic evolution.

Environmental phototoxicity: Solar ultraviolet radiation affects the toxicity of natural and man-made chemicals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larson, R.A.; Berenbaum, M.R.

1988-04-01

Ultraviolet radiation appears to be toxic to all forms of unpigmented living cells, including bacteria, protozoa, nematodes, arthropods, fish, birds, and mammals. In addition to the direct absorption of solar energy by cellular constituents, toxicity may occur because of the absorption of sunlight by xenobiotics (or by naturally occurring compounds outside the target cell); these may be converted by light or by subsequent light-promoted reactions that induce cellular damage. This article describes the phototoxicity of photodynamic dyes, light-activated synthetic herbicides, petroleum and its constituents, and naturally occurring chemicals from plants. Detoxification mechanisms are also discussed.

Hereditary Disorders with Defective Repair of UV-Induced DNA Damage

PubMed Central

Moriwaki, Shinichi

2013-01-01

Nucleotide excision repair (NER) is an essential system for correcting ultraviolet (UV)—induced DNA damage. Lesions remaining in DNA due to reduced capacity of NER may result in cellular death, premature aging, mutagenesis and carcinogenesis of the skin. So, NER is an important protection against these changes. There are three representative genodermatoses resulting from genetic defects in NER: xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD). In Japan, CS is similarly rare but XP is more common and TTD is less common compared to Western countries. In 1998, we established the system for the diagnosis of these disorders and we have been performing DNA repair and genetic analysis for more than 400 samples since then. At present, there is no cure for any human genetic disorder. Early diagnosis and symptomatic treatment of neurological, ocular and dermatological abnormalities should contribute to prolonging life and elevating QOL in patients. PMID:23966815

Ultraviolet radiation exposure from UV-transilluminators.

PubMed

Akbar-Khanzadeh, Farhang; Jahangir-Blourchian, Mahdi

2005-10-01

UV-transilluminators use ultraviolet radiation (UVR) to visualize proteins, DNA, RNA, and their precursors in a gel electrophoresis procedure. This study was initiated to evaluate workers' exposure to UVR during their use of UV-transilluminators. The levels of irradiance of UV-A, UV-B, and UV-C were determined for 29 UV-transilluminators at arbitrary measuring locations of 6, 25, 62, and 125 cm from the center of the UV-transilluminator's filter surface in the direction of the operator's head. The operators (faculty, research staff, and graduate students) worked within 62 cm of the transilluminators, with most subjects commonly working at < or =25 cm from the UV-transilluminator's filter surface. Daily exposure time ranged from 1 to 60 min. Actinic hazard (effective irradiance level of UVR) was also determined for three representative UV-transilluminators at arbitrary measuring locations of 2.5, 5, 10, 15, 20, 30, 40, and 50 cm from these sets' filter surface in the direction of the operator's head. The allowable exposure time for these instruments was less than 20 sec within 15 cm, less than 35 sec within 25 cm, and less than 2 min within 50 cm from the UV-transilluminators' filter surface. The results of this study suggest that the use of UV-transilluminators exposes operators to levels of UVR in excess of exposure guidelines. It is recommended that special safety training be provided for the affected employees and that exposure should be controlled by one or the combination of automation, substitution, isolation, posted warning signs, shielding, and/or personal protective equipment.

Improving Assessment of Lifetime Solar Ultraviolet Radiation Exposure in Epidemiologic Studies: Comparison of Ultraviolet Exposure Assessment Methods in a Nationwide United States Occupational Cohort.

PubMed

Little, Mark P; Tatalovich, Zaria; Linet, Martha S; Fang, Michelle; Kendall, Gerald M; Kimlin, Michael G

2018-06-13

Solar ultraviolet radiation is the primary risk factor for skin cancers and sun-related eye disorders. Estimates of individual ambient ultraviolet irradiance derived from ground-based solar measurements and from satellite measurements have rarely been compared. Using self-reported residential history from 67,189 persons in a nationwide occupational US radiologic technologists cohort, we estimated ambient solar irradiance using data from ground-based meters and noontime satellite measurements. The mean distance-moved from city of longest residence in childhood increased from 137.6 km at ages 13-19 to 870.3 km at ages ≥65, with corresponding increases in absolute latitude-difference moved. At ages 20/40/60/80, the Pearson/Spearman correlation coefficients of ground-based and satellite-derived solar potential ultraviolet exposure, using irradiance and cumulative radiant-exposure metrics, were high (=0.87-0.92). There was also moderate correlation (Pearson/Spearman correlation coefficients=0.51-0.60) between irradiance at birth and at last-known address, for ground-based and satellite data. Satellite-based lifetime estimates of ultraviolet radiation were generally 14-15% lower than ground-based estimates, albeit with substantial uncertainties, possibly because ground-based estimates incorporate fluctuations in cloud and ozone, which are incompletely incorporated in the single noontime satellite-overpass ultraviolet value. If confirmed elsewhere, the findings suggest that ground-based estimates may improve exposure-assessment accuracy and potentially provide new insights into ultraviolet-radiation-disease relationships in epidemiologic studies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Protective Effect of the Ethyl Acetate Fraction of Sargassum muticum Against Ultraviolet B–Irradiated Damage in Human Keratinocytes

PubMed Central

Piao, Mei Jing; Yoon, Weon Jong; Kang, Hee Kyoung; Yoo, Eun Sook; Koh, Young Sang; Kim, Dong Sam; Lee, Nam Ho; Hyun, Jin Won

2011-01-01

The aim of this study was to investigate the cytoprotective properties of the ethyl acetate fraction of Sargassum muticum (SME) against ultraviolet B (UVB)-induced cell damage in human keratinocytes (HaCaT cells). SME exhibited scavenging activity toward the 1,1-diphenyl-2-picrylhydrazyl radicals and hydrogen peroxide (H2O2) and UVB-induced intracellular reactive oxygen species (ROS). SME also scavenged the hydroxyl radicals generated by the Fenton reaction (FeSO4 + H2O2), which was detected using electron spin resonance spectrometry. In addition, SME decreased the level of lipid peroxidation that was increased by UVB radiation, and restored the level of protein expression and the activities of antioxidant enzymes that were decreased by UVB radiation. Furthermore, SME reduced UVB-induced apoptosis as shown by decreased DNA fragmentation and numbers of apoptotic bodies. These results suggest that SME protects human keratinocytes against UVB-induced oxidative stress by enhancing antioxidant activity in cells, thereby inhibiting apoptosis. PMID:22174656

DNA-targeted 2-nitroimidazoles: studies of the influence of the phenanthridine-linked nitroimidazoles, 2-NLP-3 and 2-NLP-4, on DNA damage induced by ionizing radiation.

PubMed

Buchko, Garry W; Weinfeld, Michael

2002-09-01

The nitroimidazole-linked phenanthridines 2-NLP-3 (5-[3-(2-nitro-1-imidazoyl)-propyl]-phenanthridinium bromide) and 2-NLP-4 (5-[3-(2-nitro-1-imidazoyl)-butyl]-phenanthridinium bromide) are composed of the radiosensitizer, 2-nitroimidazole, attached to the DNA intercalator phenanthridine by a 3- and 4-carbon linker, respectively. Previous in vitro assays showed both compounds to be 10-100 times more efficient as hypoxic cell radiosensitizers (based on external drug concentrations) than the untargeted 2-nitroimidazole radiosensitizer, misonidazole (Cowan et al., Radiat. Res. 127, 81-89, 1991). Here we have used a (32)P postlabeling assay and 5'-end-labeled oligonucleotide assay to compare the radiation-induced DNA damage generated in the presence of 2-NLP-3, 2-NLP-4, phenanthridine and misonidazole. After irradiation of the DNA under anoxic conditions, we observed a significantly greater level of 3'-phosphoglycolate DNA damage in the presence of 2-NLP-3 or 2-NLP-4 compared to irradiation of the DNA in the presence of misonidazole. This may account at least in part for the greater cellular radiosensitization shown by the nitroimidazole-linked phenanthridines over misonidazole. Of the two nitroimidazole-linked phenanthridines, the better in vitro radiosensitizer, 2-NLP-4, generated more 3'-phosphoglycolate in DNA than did 2-NLP-3. At all concentrations, phenanthridine had little effect on the levels of DNA damage, suggesting that the enhanced radiosensitization displayed by 2-NLP-3 and 2-NLP-4 is due to the localization of the 2-nitroimidazole to the DNA by the phenanthridine substituent and not to radiosensitization by the phenanthridine moiety itself.

Estimated Ultraviolet Radiation Doses in Wetlands in Six National Parks

EPA Science Inventory

Ultraviolet radiation (UVR) has been suggested as a potential cause of population declines and increases in malformations in amphibians. This study indicates that the present distributions of amphibians in four western U.S. National Parks are not related to UVR exposure, and sugg...

Channel catfish response to ultraviolet-B radiation

USGS Publications Warehouse

Ewing, M.S.; Blazer, V.S.; Fabacher, D.L.; Little, E.E.; Kocan, K.M.

1999-01-01

Fingerling channel catfish Ictalurus punctatus exposed to simulated ultraviolet-B radiation at an average daily dose of 2.9 J/cm2 were quite sensitive to the radiation. After a 24-h exposure, thinning of the most dorsal epidermis frequently was accompanied by edema. Compared with epidermis of unexposed fish, mucous cells in exposed fish were less superficial and club cells were less numerous both dorsally and high on the lateral surface of the body. Sunburn cells with pyknotic nuclei were evident in the epidermis of exposed fish. Among fish exposed for 48 h, focal necrosis and sloughing of the outer epidermal layer were widespread. A methanol-extractable skin substance that is associated with resistance to sunburn in other fish species was not detected in channel catfish.

Analysis of DNA repair and protection in the Tardigrade Ramazzottius varieornatus and Hypsibius dujardini after exposure to UVC radiation.

PubMed

Horikawa, Daiki D; Cumbers, John; Sakakibara, Iori; Rogoff, Dana; Leuko, Stefan; Harnoto, Raechel; Arakawa, Kazuharu; Katayama, Toshiaki; Kunieda, Takekazu; Toyoda, Atsushi; Fujiyama, Asao; Rothschild, Lynn J

2013-01-01

Tardigrades inhabiting terrestrial environments exhibit extraordinary resistance to ionizing radiation and UV radiation although little is known about the mechanisms underlying the resistance. We found that the terrestrial tardigrade Ramazzottius varieornatus is able to tolerate massive doses of UVC irradiation by both being protected from forming UVC-induced thymine dimers in DNA in a desiccated, anhydrobiotic state as well as repairing the dimers that do form in the hydrated animals. In R. varieornatus accumulation of thymine dimers in DNA induced by irradiation with 2.5 kJ/m(2) of UVC radiation disappeared 18 h after the exposure when the animals were exposed to fluorescent light but not in the dark. Much higher UV radiation tolerance was observed in desiccated anhydrobiotic R. varieornatus compared to hydrated specimens of this species. On the other hand, the freshwater tardigrade species Hypsibius dujardini that was used as control, showed much weaker tolerance to UVC radiation than R. varieornatus, and it did not contain a putative phrA gene sequence. The anhydrobiotes of R. varieornatus accumulated much less UVC-induced thymine dimers in DNA than hydrated one. It suggests that anhydrobiosis efficiently avoids DNA damage accumulation in R. varieornatus and confers better UV radiation tolerance on this species. Thus we propose that UV radiation tolerance in tardigrades is due to the both high capacities of DNA damage repair and DNA protection, a two-pronged survival strategy.

Analysis of DNA Repair and Protection in the Tardigrade Ramazzottius varieornatus and Hypsibius dujardini after Exposure to UVC Radiation

PubMed Central

Horikawa, Daiki D.; Cumbers, John; Sakakibara, Iori; Rogoff, Dana; Leuko, Stefan; Harnoto, Raechel; Arakawa, Kazuharu; Katayama, Toshiaki; Kunieda, Takekazu; Toyoda, Atsushi; Fujiyama, Asao; Rothschild, Lynn J.

2013-01-01

Tardigrades inhabiting terrestrial environments exhibit extraordinary resistance to ionizing radiation and UV radiation although little is known about the mechanisms underlying the resistance. We found that the terrestrial tardigrade Ramazzottius varieornatus is able to tolerate massive doses of UVC irradiation by both being protected from forming UVC-induced thymine dimers in DNA in a desiccated, anhydrobiotic state as well as repairing the dimers that do form in the hydrated animals. In R. varieornatus accumulation of thymine dimers in DNA induced by irradiation with 2.5 kJ/m2 of UVC radiation disappeared 18 h after the exposure when the animals were exposed to fluorescent light but not in the dark. Much higher UV radiation tolerance was observed in desiccated anhydrobiotic R. varieornatus compared to hydrated specimens of this species. On the other hand, the freshwater tardigrade species Hypsibius dujardini that was used as control, showed much weaker tolerance to UVC radiation than R. varieornatus, and it did not contain a putative phrA gene sequence. The anhydrobiotes of R. varieornatus accumulated much less UVC-induced thymine dimers in DNA than hydrated one. It suggests that anhydrobiosis efficiently avoids DNA damage accumulation in R. varieornatus and confers better UV radiation tolerance on this species. Thus we propose that UV radiation tolerance in tardigrades is due to the both high capacities of DNA damage repair and DNA protection, a two-pronged survival strategy. PMID:23762256

Vacuum-Ultraviolet photoionization studies of the microhydrationof DNA bases (Guanine, Cytosine, Adenine and Thymine)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belau, L.; Wilson, K.R.; Leone, S.R.

2007-01-22

In this work, we report on a photoionization study of the microhydration of the four DNA bases. Gas-phase clusters of water with DNA bases [guanine (G), cytosine (C), adenine (A), and thymine (T)] are generated via thermal vaporization of the bases and expansion of the resultant vapor in a continuous supersonic jet expansion of water seeded in Ar. The resulting clusters are investigated by single-photon ionization with tunable vacuum-ultraviolet synchrotron radiation and mass analyzed using reflectron mass spectrometry. Photoionization efficiency (PIE) curves are recorded for the DNA bases and the following water (W) clusters: G, GW{sub n} (n = 1-3);more » C, CW{sub n} (n = 1-3); A, AW{sub n} (n = 1,2); and T, TW{sub n} (n = 1-3). Appearance energies (AE) are derived from the onset of these PIE curves (all energies in eV): G (8.1 {+-} 0.1), GW (8.0 {+-} 0.1), GW{sub 2} (8.0 {+-} 0.1), and GW{sub 3} (8.0); C (8.65 {+-} 0.05), CW (8.45 {+-} 0.05), CW{sub 2} (8.4 {+-} 0.1), and CW{sub 3} (8.3 {+-} 0.1); A (8.30 {+-} 0.05), AW (8.20 {+-} 0.05), and AW{sub 2} (8.1 {+-} 0.1); T (8.90 {+-} 0.05); and TW (8.75 {+-} 0.05), TW{sub 2} (8.6 {+-} 0.1), and TW{sub 3} (8.6 {+-} 0.1). The AEs of the DNA bases decrease slightly with the addition of water molecules (up to three) but do not converge to values found for photoinduced electron removal from DNA bases in solution.« less

Chronic low-dose ultraviolet-induced mutagenesis in nucleotide excision repair-deficient cells.

PubMed

Haruta, Nami; Kubota, Yoshino; Hishida, Takashi

2012-09-01

UV radiation induces two major types of DNA lesions, cyclobutane pyrimidine dimers (CPDs) and 6-4 pyrimidine-pyrimidine photoproducts, which are both primarily repaired by nucleotide excision repair (NER). Here, we investigated how chronic low-dose UV (CLUV)-induced mutagenesis occurs in rad14Δ NER-deficient yeast cells, which lack the yeast orthologue of human xeroderma pigmentosum A (XPA). The results show that rad14Δ cells have a marked increase in CLUV-induced mutations, most of which are C→T transitions in the template strand for transcription. Unexpectedly, many of the CLUV-induced C→T mutations in rad14Δ cells are dependent on translesion synthesis (TLS) DNA polymerase η, encoded by RAD30, despite its previously established role in error-free TLS. Furthermore, we demonstrate that deamination of cytosine-containing CPDs contributes to CLUV-induced mutagenesis. Taken together, these results uncover a novel role for Polη in the induction of C→T transitions through deamination of cytosine-containing CPDs in CLUV-exposed NER deficient cells. More generally, our data suggest that Polη can act as both an error-free and a mutagenic DNA polymerase, depending on whether the NER pathway is available to efficiently repair damaged templates.

Tolerance of an albino fish to ultraviolet-B radiation

USGS Publications Warehouse

Fabacher, David L.; Little, Edward E.; Ostrander, Gary K.

1999-01-01

We exposed albino and pigmented medakaOryzias latipes to simulated solar ultraviolet-B (UVB) radiation to determine if albino medaka were less tolerant of UVB radiation than medaka pigmented with melanin. There was no difference in the number of albino and pigmented medaka that died during the exposure period. Spectrophotometric analyses of the outer dorsal skin layers from albino and pigmented medaka indicated that, prior to exposure, both groups of fish had similar amounts of an apparent colorless non-melanin photoprotective substance that appears to protect other fish species from UVB radiation. Our results indicate that albino medaka were as tolerant of UVB radiation as pigmented medaka because they had similar amounts of this photoprotective substance in the outer layers of the skin.

Radiation-induced double-strand breaks in mammalian DNA: influence of temperature and DMSO.

PubMed

Elmroth, K; Nygren, J; Erkell, L J; Hultborn, R

2000-11-01

To investigate the effects of subphysiological irradiation temperature (2 28 degrees C) and the influence of the radical scavenger DMSO on the induction of double-strand breaks (DSB) in chromosomal DNA from a human breast cancer cell line (MCF-7) as well as in intact cells. The rejoining of DSB in cells irradiated at 2 degrees C or 37 degrees C was also investigated. Agarose plugs with [14C]thymidine labelled MCF-7 cells were lysed in EDTA-NLS-proteinase-K buffer. The plugs containing chromosomal DNA were irradiated with X-rays under different temperatures and scavenging conditions. Intact MCF-7 cells were irradiated in Petri dishes and plugs were made. The cells were then lysed in EDTA-NLS-proteinase-K buffer. The induction of DSB was studied by constant field gel electrophoresis and expressed as DSB/100/Mbp, calculated from the fraction of activity released into the gel. The induction of DSB in chromosomal DNA was reduced by a decrease in temperature. This protective effect of low temperature was inhibited when the DNA was irradiated in the presence of DMSO. No difference was found when intact cells were irradiated at different temperatures. However, the rapid phase of rejoining was slower in cells irradiated at 37 degrees C than at 2 degrees C. The induction of DSB in naked DNA was reduced by hypothermic irradiation. The temperature had no influence on the induction of DSB in the presence of a high concentration of DMSO, indicating that the temperature effect is mediated via the indirect effects of ionizing radiation. Results are difficult to interpret in intact cells. Rejoining during irradiation at the higher temperature may counteract an increased induction. The difference in rejoining may be interpreted in terms of qualitative differences between breaks induced at the two temperatures.

Vacuum-ultraviolet photoionization studies of the microhydration of DNA bases (guanine, cytosine, adenine, and thymine).

PubMed

Belau, Leonid; Wilson, Kevin R; Leone, Stephen R; Ahmed, Musahid

2007-08-09

In this work, we report on a photoionization study of the microhydration of the four DNA bases. Gas-phase clusters of water with DNA bases [guanine (G), cytosine (C), adenine (A), and thymine (T)] are generated via thermal vaporization of the bases and expansion of the resultant vapor in a continuous supersonic jet expansion of water seeded in Ar. The resulting clusters are investigated by single-photon ionization with tunable vacuum-ultraviolet synchrotron radiation and mass analyzed using reflectron mass spectrometry. Photoionization efficiency (PIE) curves are recorded for the DNA bases and the following water (W) clusters: G, GWn (n = 1-3); C, CWn (n = 1-3); A, AWn (n = 1,2); and T, TWn (n = 1-3). Appearance energies (AE) are derived from the onset of these PIE curves (all energies in eV): G (8.1 +/- 0.1), GW (8.0 +/- 0.1), GW2 (8.0 +/- 0.1), and GW3 (8.0); C (8.65 +/- 0.05), CW (8.45 +/- 0.05), CW2 (8.4 +/- 0.1), and CW3 (8.3 +/- 0.1); A (8.30 +/- 0.05), AW (8.20 +/- 0.05), and AW2 (8.1 +/- 0.1); T (8.90 +/- 0.05); and TW (8.75 +/- 0.05), TW2 (8.6 +/- 0.1), and TW3 (8.6 +/- 0.1). The AEs of the DNA bases decrease slightly with the addition of water molecules (up to three) but do not converge to values found for photoinduced electron removal from DNA bases in solution.

Integrated molecular analysis indicates undetectable change in DNA damage in mice after continuous irradiation at ~ 400-fold natural background radiation.

PubMed

Olipitz, Werner; Wiktor-Brown, Dominika; Shuga, Joe; Pang, Bo; McFaline, Jose; Lonkar, Pallavi; Thomas, Aline; Mutamba, James T; Greenberger, Joel S; Samson, Leona D; Dedon, Peter C; Yanch, Jacquelyn C; Engelward, Bevin P

2012-08-01

In the event of a nuclear accident, people are exposed to elevated levels of continuous low dose-rate radiation. Nevertheless, most of the literature describes the biological effects of acute radiation. DNA damage and mutations are well established for their carcinogenic effects. We assessed several key markers of DNA damage and DNA damage responses in mice exposed to low dose-rate radiation to reveal potential genotoxic effects associated with low dose-rate radiation. We studied low dose-rate radiation using a variable low dose-rate irradiator consisting of flood phantoms filled with 125Iodine-containing buffer. Mice were exposed to 0.0002 cGy/min (~ 400-fold background radiation) continuously over 5 weeks. We assessed base lesions, micronuclei, homologous recombination (HR; using fluorescent yellow direct repeat mice), and transcript levels for several radiation-sensitive genes. We did not observe any changes in the levels of the DNA nucleobase damage products hypoxanthine, 8-oxo-7,8-dihydroguanine, 1,N6-ethenoadenine, or 3,N4-ethenocytosine above background levels under low dose-rate conditions. The micronucleus assay revealed no evidence that low dose-rate radiation induced DNA fragmentation, and there was no evidence of double strand break-induced HR. Furthermore, low dose-rate radiation did not induce Cdkn1a, Gadd45a, Mdm2, Atm, or Dbd2. Importantly, the same total dose, when delivered acutely, induced micronuclei and transcriptional responses. These results demonstrate in an in vivo animal model that lowering the dose-rate suppresses the potentially deleterious impact of radiation and calls attention to the need for a deeper understanding of the biological impact of low dose-rate radiation.

Silencing expression of the catalytic subunit of DNA-dependent protein kinase by small interfering RNA sensitizes human cells for radiation-induced chromosome damage, cell killing, and mutation

NASA Technical Reports Server (NTRS)

Peng, Yuanlin; Zhang, Qinming; Nagasawa, Hatsumi; Okayasu, Ryuichi; Liber, Howard L.; Bedford, Joel S.

2002-01-01

Targeted gene silencing in mammalian cells by RNA interference (RNAi) using small interfering RNAs (siRNAs) was recently described by Elbashir et al. (S. M. Elbashir et al., Nature (Lond.), 411: 494-498, 2001). We have used this methodology in several human cell strains to reduce expression of the Prkdc (DNA-PKcs) gene coding for the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) that is involved in the nonhomologous end joining of DNA double-strand breaks. We have also demonstrated a radiosensitization for several phenotypic endpoints of radiation damage. In low-passage normal human fibroblasts, siRNA knock-down of DNA-PKcs resulted in a reduced capacity for restitution of radiation-induced interphase chromosome breaks as measured by premature chromosome condensation, an increased yield of acentric chromosome fragments at the first postirradiation mitosis, and an increased radiosensitivity for cell killing. For three strains of related human lymphoblasts, DNA-PKcs-targeted siRNA transfection resulted in little or no increase in radiosensitivity with respect to cell killing, a 1.5-fold decrease in induced mutant yield in TK6- and p53-null NH32 cells, but about a 2-fold increase in induced mutant yield in p53-mutant WTK1 cells at both the hypoxanthine quanine phosphoribosyl transferase (hprt) and the thymidine kinase loci.

The ultraviolet radiation environment of pollen and its effect on pollen germination

NASA Technical Reports Server (NTRS)

1981-01-01

The damage to pollen caused by natural ultraviolet radiation was investigated. Experimental and literature research into the UV radiation environment is reported. Viability and germination of wind and insect pollinated species were determined. Physiological, developmental, and protective factors influencing UV sensitivity of binucleate, advanced binucleate, and trinucleate pollen grains are compared.

MECHANISMS OF PLANT RESISTANCE TO INCREASED SOLAR ULTRAVIOLET-B RADIATION

EPA Science Inventory

Since the major conclusions of the project are being disseminated via the scientific literature, the final report consists of a compilation of 11 articles and manuscripts on the effects of ultraviolet-B radiation (UVB) on soybean growth and yield, stress interactions with UVB, an...

Vacuum ultraviolet radiation effects on two-dimensional MoS2 field-effect transistors

NASA Astrophysics Data System (ADS)

McMorrow, Julian J.; Cress, Cory D.; Arnold, Heather N.; Sangwan, Vinod K.; Jariwala, Deep; Schmucker, Scott W.; Marks, Tobin J.; Hersam, Mark C.

2017-02-01

Atomically thin MoS2 has generated intense interest for emerging electronics applications. Its two-dimensional nature and potential for low-power electronics are particularly appealing for space-bound electronics, motivating the need for a fundamental understanding of MoS2 electronic device response to the space radiation environment. In this letter, we quantify the response of MoS2 field-effect transistors (FETs) to vacuum ultraviolet (VUV) total ionizing dose radiation. Single-layer (SL) and multilayer (ML) MoS2 FETs are compared to identify differences that arise from thickness and band structure variations. The measured evolution of the FET transport properties is leveraged to identify the nature of VUV-induced trapped charge, isolating the effects of the interface and bulk oxide dielectric. In both the SL and ML cases, oxide trapped holes compete with interface trapped electrons, exhibiting an overall shift toward negative gate bias. Raman spectroscopy shows no variation in the MoS2 signatures as a result of VUV exposure, eliminating significant crystalline damage or oxidation as possible radiation degradation mechanisms. Overall, this work presents avenues for achieving radiation-hard MoS2 devices through dielectric engineering that reduces oxide and interface trapped charge.

Light-induced pyroelectric effect as an effective approach for ultrafast ultraviolet nanosensing

NASA Astrophysics Data System (ADS)

Wang, Zhaona; Yu, Ruomeng; Pan, Caofeng; Li, Zhaoling; Yang, Jin; Yi, Fang; Wang, Zhong Lin

2015-09-01

Zinc oxide is potentially a useful material for ultraviolet detectors; however, a relatively long response time hinders practical implementation. Here by designing and fabricating a self-powered ZnO/perovskite-heterostructured ultraviolet photodetector, the pyroelectric effect, induced in wurtzite ZnO nanowires on ultraviolet illumination, has been utilized as an effective approach for high-performance photon sensing. The response time is improved from 5.4 s to 53 μs at the rising edge, and 8.9 s to 63 μs at the falling edge, with an enhancement of five orders in magnitudes. The specific detectivity and the responsivity are both enhanced by 322%. This work provides a novel design to achieve ultrafast ultraviolet sensing at room temperature via light-self-induced pyroelectric effect. The newly designed ultrafast self-powered ultraviolet nanosensors may find promising applications in ultrafast optics, nonlinear optics, optothermal detections, computational memories and biocompatible optoelectronic probes.

The Analysis of the Patterns of Radiation-Induced DNA Damage Foci by a Stochastic Monte Carlo Model of DNA Double Strand Breaks Induction by Heavy Ions and Image Segmentation Software

NASA Technical Reports Server (NTRS)

Ponomarev, Artem; Cucinotta, F.

2011-01-01

To create a generalized mechanistic model of DNA damage in human cells that will generate analytical and image data corresponding to experimentally observed DNA damage foci and will help to improve the experimental foci yields by simulating spatial foci patterns and resolving problems with quantitative image analysis. Material and Methods: The analysis of patterns of RIFs (radiation-induced foci) produced by low- and high-LET (linear energy transfer) radiation was conducted by using a Monte Carlo model that combines the heavy ion track structure with characteristics of the human genome on the level of chromosomes. The foci patterns were also simulated in the maximum projection plane for flat nuclei. Some data analysis was done with the help of image segmentation software that identifies individual classes of RIFs and colocolized RIFs, which is of importance to some experimental assays that assign DNA damage a dual phosphorescent signal. Results: The model predicts the spatial and genomic distributions of DNA DSBs (double strand breaks) and associated RIFs in a human cell nucleus for a particular dose of either low- or high-LET radiation. We used the model to do analyses for different irradiation scenarios. In the beam-parallel-to-the-disk-of-a-flattened-nucleus scenario we found that the foci appeared to be merged due to their high density, while, in the perpendicular-beam scenario, the foci appeared as one bright spot per hit. The statistics and spatial distribution of regions of densely arranged foci, termed DNA foci chains, were predicted numerically using this model. Another analysis was done to evaluate the number of ion hits per nucleus, which were visible from streaks of closely located foci. In another analysis, our image segmentaiton software determined foci yields directly from images with single-class or colocolized foci. Conclusions: We showed that DSB clustering needs to be taken into account to determine the true DNA damage foci yield, which helps to

Effect of Lot Variability on Ultraviolet Radiation Inactivation Kinetics of Cryptosporidium parvum Oocysts

EPA Science Inventory

Numerous studies have demonstrated the efficiency of ultraviolet (UV) radiation for the inactivation of oocysts of Cryptosporidium parvum. In these studies inactivation is measured as reduction in oocysts. A primary goal is to estimate the UV radiation required to achiev...

UV-B Radiation Induces Root Bending Through the Flavonoid-Mediated Auxin Pathway in Arabidopsis

PubMed Central

Wan, Jinpeng; Zhang, Ping; Wang, Ruling; Sun, Liangliang; Wang, Wenying; Zhou, Huakun; Xu, Jin

2018-01-01

Ultraviolet (UV)-B radiation-induced root bending has been reported; however, the underlying mechanisms largely remain unclear. Here, we investigate whether and how auxin and flavonoids are involved in UV-B radiation-induced root bending in Arabidopsis using physiological, pharmacological, and genetic approaches. UV-B radiation modulated the direction of root growth by decreasing IAA biosynthesis and affecting auxin distribution in the root tips, where reduced auxin accumulation and asymmetric auxin distribution were observed. UV-B radiation increased the distribution of auxin on the nonradiated side of the root tips, promoting growth and causing root bending. Further analysis indicated that UV-B induced an asymmetric accumulation of flavonoids; this pathway is involved in modulating the accumulation and asymmetric distribution of auxin in root tips and the subsequent redirection of root growth by altering the distribution of auxin carriers in response to UV-B radiation. Taken together, our results indicate that UV-B radiation-induced root bending occurred through a flavonoid-mediated phototropic response to UV-B radiation. PMID:29868074

Quantitation of Radiation Induced Deletion and Recombination Events Associated with Repeated DNA Sequences

NASA Technical Reports Server (NTRS)

Sinden, Richard R.

1999-01-01

Manned exploration of space exposes the explorers to a complex and novel radiation environment. The galactic cosmic ray and trapped belt radiation (predominantly proton) components of this environment are relatively constant, and the variations with the solar cycle are well understood and predictable. The level of radiation encountered in low earth orbits is determined by several factors, including altitude, inclination of orbit with respect to the equator, and spacecraft shielding. At higher altitudes, and on a Mars mission, the level of radiation exposure will increase significantly. A significant fraction of the dose may be delivered by solar particle events which vary dramatically in dose rate and incident particle spectrum. High-LET radiation is of particular concern. High-LET radiation, a component of galactic cosmic rays (GCR), is comprised of a variety of charged particles of various energies (10 MeV/n to 10 GeV/n), including about 87% photons, 12% helium ions, and heavy ions (including iron). These high energy particles can cause significant damage to target cells. The different particle types and energies result in different patterns of energy deposition at the molecular and cellular level in a primary target cell. They can also cause significant damage to other, nearby cells as a result of secondary particles. Protons, for instance produce secondaries that include photons, neutrons, pions, heavy particles, as well as gamma rays. Heavy ions deposit energy in a "track" in which the magnitude of the damage varies as the particle loses energy. Heavy ions produce secondary delta rays, or electrons. The distribution of damage through tissue is described by a Bragg curve which will be characteristic for different energies. Needless to say there are differences in the RBE of protons and a particles. High-LET heavy ions are particularly damaging to cells as they do continual damage throughout their track. Differences in these energy deposition patterns can

Biological Effects of Sunlight, Ultraviolet Radiation, Visible Light, Infrared Radiation and Vitamin D for Health.

PubMed

Holick, Michael F

2016-03-01

Humans evolved in sunlight and had depended on sunlight for its life giving properties that was appreciated by our early ancestors. However, for more than 40 years the lay press and various medical and dermatology associations have denounced sun exposure because of its association with increased risk for skin cancer. The goal of this review is to put into perspective the many health benefits that have been associated with exposure to sunlight, ultraviolet A (UVA) ultraviolet B (UVB), visible and infrared radiation. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Factors influencing heterogeneity of radiation-induced DNA-damage measured by the alkaline comet assay.

PubMed

Seidel, Clemens; Lautenschläger, Christine; Dunst, Jürgen; Müller, Arndt-Christian

2012-04-20

To investigate whether different conditions of DNA structure and radiation treatment could modify heterogeneity of response. Additionally to study variance as a potential parameter of heterogeneity for radiosensitivity testing. Two-hundred leukocytes per sample of healthy donors were split into four groups. I: Intact chromatin structure; II: Nucleoids of histone-depleted DNA; III: Nucleoids of histone-depleted DNA with 90 mM DMSO as antioxidant. Response to single (I-III) and twice (IV) irradiation with 4 Gy and repair kinetics were evaluated using %Tail-DNA. Heterogeneity of DNA damage was determined by calculation of variance of DNA-damage (V) and mean variance (Mvar), mutual comparisons were done by one-way analysis of variance (ANOVA). Heterogeneity of initial DNA-damage (I, 0 min repair) increased without histones (II). Absence of histones was balanced by addition of antioxidants (III). Repair reduced heterogeneity of all samples (with and without irradiation). However double irradiation plus repair led to a higher level of heterogeneity distinguishable from single irradiation and repair in intact cells. Increase of mean DNA damage was associated with a similarly elevated variance of DNA damage (r = +0.88). Heterogeneity of DNA-damage can be modified by histone level, antioxidant concentration, repair and radiation dose and was positively correlated with DNA damage. Experimental conditions might be optimized by reducing scatter of comet assay data by repair and antioxidants, potentially allowing better discrimination of small differences. Amount of heterogeneity measured by variance might be an additional useful parameter to characterize radiosensitivity.

Factors influencing heterogeneity of radiation-induced DNA-damage measured by the alkaline comet assay

PubMed Central

2012-01-01

Background To investigate whether different conditions of DNA structure and radiation treatment could modify heterogeneity of response. Additionally to study variance as a potential parameter of heterogeneity for radiosensitivity testing. Methods Two-hundred leukocytes per sample of healthy donors were split into four groups. I: Intact chromatin structure; II: Nucleoids of histone-depleted DNA; III: Nucleoids of histone-depleted DNA with 90 mM DMSO as antioxidant. Response to single (I-III) and twice (IV) irradiation with 4 Gy and repair kinetics were evaluated using %Tail-DNA. Heterogeneity of DNA damage was determined by calculation of variance of DNA-damage (V) and mean variance (Mvar), mutual comparisons were done by one-way analysis of variance (ANOVA). Results Heterogeneity of initial DNA-damage (I, 0 min repair) increased without histones (II). Absence of histones was balanced by addition of antioxidants (III). Repair reduced heterogeneity of all samples (with and without irradiation). However double irradiation plus repair led to a higher level of heterogeneity distinguishable from single irradiation and repair in intact cells. Increase of mean DNA damage was associated with a similarly elevated variance of DNA damage (r = +0.88). Conclusions Heterogeneity of DNA-damage can be modified by histone level, antioxidant concentration, repair and radiation dose and was positively correlated with DNA damage. Experimental conditions might be optimized by reducing scatter of comet assay data by repair and antioxidants, potentially allowing better discrimination of small differences. Amount of heterogeneity measured by variance might be an additional useful parameter to characterize radiosensitivity. PMID:22520045

Skin Erythema, Pigmentation and Hydration Kinetics after Ultraviolet Radiation-induced Photodamage in Southern Chinese Women.

PubMed

Wan, Miaojian; Hu, Rong; Xie, Xiaoyuan; Gong, Zijian; Yi, Jinling; Chen, Haiyan; Xie, Lin; Guan, Xiaomin; Guan, Lei; Lai, Wei

2017-10-01

Although there have been some studies about changes of skin erythema and pigmentation following ultraviolet radiation in other races, the relevant data in Chinese have never been achieved. Thus, we evaluated the long-time course of skin erythema, pigmentation and hydration changes after different doses of solar-simulated ultraviolet (SSUV) irradiation in 26 Chinese women for 168 days. The erythema index increased abruptly and peaked during 3 days of SSUV exposure, then slowly returned to the baseline level starting at day 7 and completely recovered during 168-day course of this study only in one minimal erythema doses (MED) SSUV irradiation. The melanin index started to slowly increase at day 3 of SSUV exposure, peaking at day 14 and gradually returned to the baseline level thereafter, but did not return to the baseline level during 168-day course in all doses. Skin hydration slowly declined at day 3 of exposure, hitting the lowest point at day 7, then slowly recovered starting at day 14 and completely returned to the baseline level at day 28 only in 1.5MED. These results will serve as baseline data on Chinese skin and provide useful references for the treatment of serious skin photodamage in Chinese. © 2017 The American Society of Photobiology.

Stress-Induced Sleep After Exposure to Ultraviolet Light Is Promoted by p53 in Caenorhabditis elegans.

PubMed

DeBardeleben, Hilary K; Lopes, Lindsey E; Nessel, Mark P; Raizen, David M

2017-10-01

Stress-induced sleep (SIS) in Caenorhabditis elegans is important for restoration of cellular homeostasis and is a useful model to study the function and regulation of sleep. SIS is triggered when epidermal growth factor (EGF) activates the ALA neuron, which then releases neuropeptides to promote sleep. To further understand this behavior, we established a new model of SIS using irradiation by ultraviolet C (UVC) light. While UVC irradiation requires ALA signaling and leads to a sleep state similar to that induced by heat and other stressors, it does not induce the proteostatic stress seen with heat exposure. Based on the known genotoxic effects of UVC irradiation, we tested two genes, atl-1 and cep-1 , which encode proteins that act in the DNA damage response pathway. Loss-of-function mutants of atl-1 had no defect in UVC-induced SIS but a partial loss-of-function mutant of cep-1 , gk138 , had decreased movement quiescence following UVC irradiation. Germline ablation experiments and tissue-specific RNA interference experiments showed that cep-1 is required somatically in neurons for its effect on SIS. The cep-1 ( gk138 ) mutant suppressed body movement quiescence controlled by EGF, indicating that CEP-1 acts downstream or in parallel to ALA activation to promote quiescence in response to ultraviolet light. Copyright © 2017 by the Genetics Society of America.

Plasma induced DNA damage: Comparison with the effects of ionizing radiation

NASA Astrophysics Data System (ADS)

Lazović, S.; Maletić, D.; Leskovac, A.; Filipović, J.; Puač, N.; Malović, G.; Joksić, G.; Petrović, Z. Lj.

2014-09-01

We use human primary fibroblasts for comparing plasma and gamma rays induced DNA damage. In both cases, DNA strand breaks occur, but of fundamentally different nature. Unlike gamma exposure, contact with plasma predominantly leads to single strand breaks and base-damages, while double strand breaks are mainly consequence of the cell repair mechanisms. Different cell signaling mechanisms are detected confirming this (ataxia telangiectasia mutated - ATM and ataxia telangiectasia and Rad3 related - ATR, respectively). The effective plasma doses can be tuned to match the typical therapeutic doses of 2 Gy. Tailoring the effective dose through plasma power and duration of the treatment enables safety precautions mainly by inducing apoptosis and consequently reduced frequency of micronuclei.

The relationship between ultraviolet radiation exposure and vitamin D status.

PubMed

Engelsen, Ola

2010-05-01

This paper reviews the main factors influencing the synthesis of vitamin D, with particular focus on ultraviolet radiation exposure. On the global level, the main source of vitamin D is the sun. The effect of solar radiation on vitamin D synthesis depends to some extent on the initial vitamin D levels. At moderate to high latitudes, diet becomes an increasingly important source of vitamin D due to decreased solar intensity and cold temperatures, which discourage skin exposure. During the mid-winter season, these factors result in decreased solar radiation exposure, hindering extensively the synthesis of vitamin D in these populations.

Effects of a Mangifera indica L. stem bark extract and mangiferin on radiation-induced DNA damage in human lymphocytes and lymphoblastoid cells.

PubMed

Rodeiro, I; Delgado, R; Garrido, G

2014-02-01

Mangifera indica L. (mango) stem bark aqueous extract (MSBE) that has antioxidant, anti-inflammatory and immunomodulatory properties, can be obtained in Cuba. It is rich in polyphenols, where mangiferin is the main component. In this study, we have tested DNA damage and protection effects of MSBE and mangiferin on primary human lymphocytes and lymphoblastoid cells. Cell suspensions were incubated with the products (50-1000 μg/ml) for experiments on damage induction, and evaluation of any potential protective effects (5-100 μg/ml) for 60 min at 37 °C. Irradiation was performed using a γ-ray source, absorbed dose 5 Gy. At the end of exposure, DNA damage, protection and repair processes were evaluated using the comet assay. MSBE (100-1000 μg/ml) induced DNA damage in a concentration dependent manner in both cell types tested, primary cells being more sensitive. Mangiferin (200 μg/ml) only induced light DNA damage at higher concentrations. DNA repair capacity was not affected after MSBE or mangiferin exposure. On the other hand, MSBE (25 and 50 μg/ml) and mangiferin (5-25 ug/ml) protected against gamma radiation-induced DNA damage. These results show MSBE has protector or harmful effects on DNA in vitro depending on the experimental conditions, which suggest that the extract could be acting as an antioxidant or pro-oxidant product. Mangiferin was involved in protective effects of the extract. © 2013 John Wiley & Sons Ltd.

Mobile phone radiation induces mode-dependent DNA damage in a mouse spermatocyte-derived cell line: a protective role of melatonin.

PubMed

Liu, Chuan; Gao, Peng; Xu, Shang-Cheng; Wang, Yuan; Chen, Chun-Hai; He, Min-Di; Yu, Zheng-Ping; Zhang, Lei; Zhou, Zhou

2013-11-01

To evaluate whether exposure to mobile phone radiation (MPR) can induce DNA damage in male germ cells. A mouse spermatocyte-derived GC-2 cell line was exposed to a commercial mobile phone handset once every 20 min in standby, listen, dialed or dialing modes for 24 h. DNA damage was determined using an alkaline comet assay. The levels of DNA damage were significantly increased following exposure to MPR in the listen, dialed and dialing modes. Moreover, there were significantly higher increases in the dialed and dialing modes than in the listen mode. Interestingly, these results were consistent with the radiation intensities of these modes. However, the DNA damage effects of MPR in the dialing mode were efficiently attenuated by melatonin pretreatment. These results regarding mode-dependent DNA damage have important implications for the safety of inappropriate mobile phone use by males of reproductive age and also suggest a simple preventive measure: Keeping mobile phones as far away from our body as possible, not only during conversations but during 'dialed' and 'dialing' operation modes. Since the 'dialed' mode is actually part of the standby mode, mobile phones should be kept at a safe distance from our body even during standby operation. Furthermore, the protective role of melatonin suggests that it may be a promising pharmacological candidate for preventing mobile phone use-related reproductive impairments.

Radiation induced genome instability: multiscale modelling and data analysis

NASA Astrophysics Data System (ADS)

Andreev, Sergey; Eidelman, Yuri

2012-07-01

Genome instability (GI) is thought to be an important step in cancer induction and progression. Radiation induced GI is usually defined as genome alterations in the progeny of irradiated cells. The aim of this report is to demonstrate an opportunity for integrative analysis of radiation induced GI on the basis of multiscale modelling. Integrative, systems level modelling is necessary to assess different pathways resulting in GI in which a variety of genetic and epigenetic processes are involved. The multilevel modelling includes the Monte Carlo based simulation of several key processes involved in GI: DNA double strand breaks (DSBs) generation in cells initially irradiated as well as in descendants of irradiated cells, damage transmission through mitosis. Taking the cell-cycle-dependent generation of DNA/chromosome breakage into account ensures an advantage in estimating the contribution of different DNA damage response pathways to GI, as to nonhomologous vs homologous recombination repair mechanisms, the role of DSBs at telomeres or interstitial chromosomal sites, etc. The preliminary estimates show that both telomeric and non-telomeric DSB interactions are involved in delayed effects of radiation although differentially for different cell types. The computational experiments provide the data on the wide spectrum of GI endpoints (dicentrics, micronuclei, nonclonal translocations, chromatid exchanges, chromosome fragments) similar to those obtained experimentally for various cell lines under various experimental conditions. The modelling based analysis of experimental data demonstrates that radiation induced GI may be viewed as processes of delayed DSB induction/interaction/transmission being a key for quantification of GI. On the other hand, this conclusion is not sufficient to understand GI as a whole because factors of DNA non-damaging origin can also induce GI. Additionally, new data on induced pluripotent stem cells reveal that GI is acquired in normal mature

ZRBA1, a Mixed EGFR/DNA Targeting Molecule, Potentiates Radiation Response Through Delayed DNA Damage Repair Process in a Triple Negative Breast Cancer Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heravi, Mitra; Department of Radiation Oncology, McGill University, Montreal; Segal Cancer Center, Jewish General Hospital, Montreal

2015-06-01

Purpose: ZRBA1 is a combi-molecule designed to induce DNA alkylating lesions and to block epidermal growth factor receptor (EGFR) TK domain. Inasmuch as ZRBA1 downregulates the EGFR TK-mediated antisurvival signaling and induces DNA damage, we postulated that it might be a radiosensitizer. The aim of this study was to further investigate the potentiating effect of ZRBA1 in combination with radiation and to elucidate the possible mechanisms of interaction between these 2 treatment modalities. Methods and Materials: The triple negative human breast MDA-MB-468 cancer cell line and mouse mammary cancer 4T1 cell line were used in this study. Clonogenic assay, Westernmore » blot analysis, and DNA damage analysis were performed at multiple time points after treatment. To confirm our in vitro findings, in vivo tumor growth delay assay was performed. Results: Our results show that a combination of ZRBA1 and radiation increases the radiation sensitivity of both cell lines significantly with a dose enhancement factor of 1.56, induces significant numbers of DNA strand breaks, prolongs higher DNA damage up to 24 hours after treatment, and significantly increases tumor growth delay in a syngeneic mouse model. Conclusions: Our data suggest that the higher efficacy of this combination could be partially due to increased DNA damage and delayed DNA repair process and to the inhibition of EGFR. The encouraging results of this combination demonstrated a significant improvement in treatment efficiency and therefore could be applicable in early clinical trial settings.« less

Protective effect of crocin on ultraviolet B‑induced dermal fibroblast photoaging.

PubMed

Deng, Mingwu; Li, Dong; Zhang, Yichen; Zhou, Guangdong; Liu, Wei; Cao, Yilin; Zhang, Wenjie

2018-06-11

Ultraviolet B (UVB) radiation induces the production of reactive oxygen species (ROS), resulting in the aging of dermal fibroblasts. Crocin, a bioactive constituent of Crocus sativus, possesses anti‑oxidation effects. The purpose of the present study was to evaluate the protective effect of crocin on UVB‑induced dermal fibroblast photoaging. Human dermal fibroblasts were isolated and cultured with different concentrations of crocin prior to and following exposure to UVB irradiation. The senescent phenotypes of cells were evaluated, including cell proliferation, cell cycle, senescence‑associated β‑galactosidase (SA‑β‑gal) expression, intracellular ROS, expression of antioxidant protein glutathione peroxidase 1 (GPX‑1) and extracellular matrix protein collagen type 1 (Col‑1). Crocin rescued the cell proliferation inhibited by UVB irradiation, prevented cell cycle arrest and markedly decreased the number of SA‑β‑gal‑positive cells. In addition, crocin reduced UVB‑induced ROS by increasing GPX‑1 expression and other direct neutralization effects. Furthermore, crocin promoted the expression of the extracellular matrix protein Col‑1. Crocin could effectively prevent UVB‑induced cell damage via the reduction of intracellular ROS; thus, it could potentially be used in the prevention of skin photoaging.

Adverse effects of ultraviolet radiation from the use of indoor tanning equipment: time to ban the tan.

PubMed

Lim, Henry W; James, William D; Rigel, Darrell S; Maloney, Mary E; Spencer, James M; Bhushan, Reva

2011-04-01

The incidence of melanoma skin cancer is increasing rapidly, particularly among young women in the United States. Numerous studies have documented an association between the use of indoor tanning devices and an increased risk of skin cancer, especially in young women. Studies have shown that ultraviolet exposure, even in the absence of erythema or burn, results in DNA damage. Countries and regulatory bodies worldwide have recognized the health risks associated with indoor tanning. In the United States, 32 states have passed legislation to regulate the indoor tanning industry, but there is an urgent need to restrict the use of indoor tanning devices at the federal level. The Food and Drug Administration is currently reviewing the classification of these devices. For all of these reasons, the Food and Drug Administration should prohibit the use of tanning devices by minors and reclassify tanning devices to at least class II to protect the public from the preventable cancers and other adverse effects caused by ultraviolet radiation from indoor tanning. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

The effects of quercetin-loaded PLGA-TPGS nanoparticles on ultraviolet B-induced skin damages in vivo.

PubMed

Zhu, Xianbing; Zeng, Xiaowei; Zhang, Xudong; Cao, Wei; Wang, Yilin; Chen, Houjie; Wang, Teng; Tsai, Hsiang-I; Zhang, Ran; Chang, Danfeng; He, Shuai; Mei, Lin; Shi, Xiaojun

2016-04-01

Ultraviolet (UV) radiation has deleterious effects on living organisms, and functions as a tumor initiator and promoter. Multiple natural compounds, like quercetin, have been shown the protective effects on UV-induced damage. However, quercetin is extremely hydrophobic and limited by its poor percutaneous permeation and skin deposition. Here, we show that quercetin-loaded PLGA-TPGS nanoparticles could overcome low hydrophilicity of quercetin and improve its anti-UVB effect. Quercetin-loaded NPs can significantly block UVB irradiation induced COX-2 up-expression and NF-kB activation in Hacat cell line. Moreover, PLGA-TPGS NPs could efficiently get through epidermis and reach dermis. Treatment of mice with quercetin-loaded NPs also attenuates UVB irradiation-associated macroscopic and histopathological changes in mice skin. These results demonstrated that copolymer PLGA-TPGS could be used as drug nanocarriers against skin damage and disease. The findings provide an external use of PLGA-TPGS nanocarriers for application in the treatment of skin diseases. Skin is the largest organ in the body and is subjected to ultraviolet (UV) radiation damage daily from the sun. Excessive exposure has been linked to the development of skin cancer. Hence, topically applied agents can play a major role in skin protection. In this article, the authors developed quercetin-loaded PLGA-TPGS nanoparticles and showed their anti-UVB effect. Copyright © 2015 Elsevier Inc. All rights reserved.

Molecular DNA-based detection of ionising radiation in meat.

PubMed

Şakalar, Ergün

2017-05-01

Ionising radiation induces molecular alterations, such as formation of ions, free radicals, and new stable molecules, and cleavage of the chemical bonds of the molecules present in food. Irradiation-treated meat should be labelled to control the process and to ensure free consumer choice. Therefore, sensitive analytical methods are required to detect the irradiation dose. Meat samples were exposed to radiation doses of 0, 0.272, 0.497, 1.063, 3.64, 8.82 and 17.42 kGy in an industrial 60 Co gamma cell. Primers were designed to amplify 998, 498 and 250-base pair (bp) regions of the 18S rRNA gene of nuclear DNA from the irradiated samples. A new DNA-based method was developed to quantify the radiation exposed to the unstored meat and the meat stored at -20 °C for 3 and 6 months. The method was able to detect meat samples stored and unstored with dose limits of 1.063 and 3.64 kGy, respectively. The level of irradiation can be detected using primer pairs that target particularly different-sized sequences for DNA amplification by PCR. This method can be widely used for the analysis of not only meat samples, but also all biological materials containing DNA. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Epigenetic dysregulation of key developmental genes in radiation-induced rat mammary carcinomas.

PubMed

Daino, Kazuhiro; Nishimura, Mayumi; Imaoka, Tatsuhiko; Takabatake, Masaru; Morioka, Takamitsu; Nishimura, Yukiko; Shimada, Yoshiya; Kakinuma, Shizuko

2018-02-13

With the increase in the number of long-term cancer survivors worldwide, there is a growing concern about the risk of secondary cancers induced by radiotherapy. Epigenetic modifications of genes associated with carcinogenesis are attractive targets for the prevention of cancer owing to their reversible nature. To identify genes with possible changes in functionally relevant DNA methylation patterns in mammary carcinomas induced by radiation exposure, we performed microarray-based global DNA methylation and expression profiling in γ-ray-induced rat mammary carcinomas and normal mammary glands. The gene expression profiling identified dysregulation of developmentally related genes, including the downstream targets of polycomb repressive complex 2 (PRC2) and overexpression of enhancer of zeste homolog 2, a component of PRC2, in the carcinomas. By integrating expression and DNA methylation profiles, we identified ten hypermethylated and three hypomethylated genes that possibly act as tumor-suppressor genes and oncogenes dysregulated by aberrant DNA methylation; half of these genes encode developmental transcription factors. Bisulfite sequencing and quantitative PCR confirmed the dysregulation of the polycomb-regulated developmentally related transcription-factor genes Dmrt2, Hoxa7, Foxb1, Sox17, Lhx8, Gata3 and Runx1. Silencing of Hoxa7 was further verified by immunohistochemistry. These results suggest that, in radiation-induced mammary gland carcinomas, PRC2-mediated aberrant DNA methylation leads to dysregulation of developmentally related transcription-factor genes. Our findings provide clues to molecular mechanisms linking epigenetic regulation and radiation-induced breast carcinogenesis and underscore the potential of such epigenetic mechanisms as targets for cancer prevention. © 2018 UICC.

Ionizing radiation induces O6-alkylguanine-DNA-alkyltransferase mRNA and activity in mouse tissues.

PubMed

Wilson, R E; Hoey, B; Margison, G P

1993-04-01

The effect of exposure to whole-body gamma-irradiation or fast electrons on O6-alkylguanine-DNA-alkyltransferase (ATase) activity and mRNA abundance has been examined in mice. In response to gamma-radiation, hepatic ATase activity was significantly raised in BDF1 mice 24 h post-irradiation, reaching a maximum of 2- to 3-fold at 36 h and beginning to decrease by 48-60 h. A small but consistently higher level of induction was achieved when mice were exposed using a low dose rate (0.015 Gy/min) compared to a high dose rate (0.5 Gy/min). ATase activity was also induced approximately 2-fold 48 h post-irradiation in brain, kidney, lung and spleen, with a greater induction again observed in response to the lower dose rate. In response to fast electrons from a linear accelerator hepatic ATase activity was also induced 2- to 3-fold 48 h post-irradiation in BDF1, BALB/c, C57Bl and DBA2 strains. Induction of ATase activity in livers of BDF1 mice was observed 48 h after a total single dose of 5 Gy gamma-radiation (2-fold), increasing to a slightly higher level at 15 Gy, but no induction was observed at doses of 2 Gy and below. Although a maximum 2- to 3-fold induction of ATase activity was observed, mRNA levels were induced 3- to 4-fold by 48 h after a dose of 15 Gy. Furthermore, significant increases in mRNA levels were detected at low doses (1-2 Gy) at which there was no apparent increase in ATase activity. This suggests that ionizing radiation increases ATase levels by a process involving transcriptional upregulation but that strong post-transcriptional and/or translational controls operate to limit induction of enzyme activity to 2- to 3-fold. This is the first report of an in vivo induction of ATase by ionizing radiation in a species other than the rat.

Norathyriol Suppresses Skin Cancers Induced by Solar Ultraviolet Radiation by Targeting ERK Kinases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Jixia; Malakhova, Margarita; Mottamal, Madhusoodanan

Ultraviolet (UV) irradiation is the leading factor in the development of skin cancer, prompting great interest in chemopreventive agents for this disease. In this study, we report the discovery of norathyriol, a plant-derived chemopreventive compound identified through an in silico virtual screening of the Chinese Medicine Library. Norathyriol is a metabolite of mangiferin found in mango, Hypericum elegans, and Tripterospermum lanceolatum and is known to have anticancer activity. Mechanistic investigations determined that norathyriol acted as an inhibitor of extracellular signal-regulated kinase (ERK)1/2 activity to attenuate UVB-induced phosphorylation in mitogen-activated protein kinases signaling cascades. We confirmed the direct and specific bindingmore » of norathyriol with ERK2 through a cocrystal structural analysis. The xanthone moiety in norathyriol acted as an adenine mimetic to anchor the compound by hydrogen bonds to the hinge region of the protein ATP-binding site on ERK2. Norathyriol inhibited in vitro cell growth in mouse skin epidermal JB6 P+ cells at the level of G{sub 2}-M phase arrest. In mouse skin tumorigenesis assays, norathyriol significantly suppressed solar UV-induced skin carcinogenesis. Further analysis indicated that norathyriol mediates its chemopreventive activity by inhibiting the ERK-dependent activity of transcriptional factors AP-1 and NF-{kappa}B during UV-induced skin carcinogenesis. Taken together, our results identify norathyriol as a safe new chemopreventive agent that is highly effective against development of UV-induced skin cancer.« less