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Sample records for repair sublethal radiation

  1. Extra lethal damage due to residual incompletely repaired sublethal damage in hyperfractionated and continuous radiation treatment

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    Chen, J.; van de Geijn, J.; Goffman, T. (ROB, DCT, NCI, NIH, Bethesda, Maryland 20892 (US))

    1991-05-01

    In the conventional linear--quadratic model of single-dose response, the {alpha} and {beta} terms reflect lethal damage created {ital during} the delivery of a dose, from two different presumed molecular processes, one linear with dose, the other quadratic. With the conventional one-fraction-per-day (or less) regimens, the sublethal damage (SLD), presumably repairing exponentially over time, is essentially completely fixed by the time of the next dose of radiation. If this assumption is true, the effects of subsequent fractions of radiation should be independent, that is, there should be little, if any, reversible damage left from previous fractions, at the time of the next dose. For multiple daily fractions, or for the limiting case, continuous radiation, this simplification may overlook damaged cells that have had insufficient time for repair. A generalized method is presented for accounting for extra lethal damage (ELD) arising from such residual SLD for hyperfractionation and continuous irradiation schemes. It may help to predict differences in toxicity and tumor control, if any, obtained with unconventional'' treatment regimens. A key element in the present model is the finite size and the dynamic character of the pool of sublethal damage. Besides creating the usual linear and quadratic components of lethal damage, each new fraction converts a certain fraction of the existing SLD into ELD, and creates some new SLD.

  2. Radiosensitivity and capacity for radiation-induced sublethal damage repair of canine transitional cell carcinoma (TCC) cell lines.

    Science.gov (United States)

    Parfitt, S L; Milner, R J; Salute, M E; Hintenlang, D E; Farese, J P; Bacon, N J; Bova, F J; Rajon, D A; Lurie, D M

    2011-09-01

    Understanding the inherent radiosensitivity and repair capacity of canine transitional cell carcinoma (TCC) can aid in optimizing radiation protocols to treat this disease. The objective of this study was to evaluate the parameters surviving fraction at 2 Gy (SF(2) ), α/β ratio and capacity for sublethal damage repair (SLDR) in response to radiation. Dose-response and split-dose studies were performed using the clonogenic assay. The mean SF(2) for three established TCC cell lines was high at 0.61. All the three cell lines exhibited a low to moderate α/β ratio, with the mean being 3.27. Two cell lines exhibited statistically increased survival at 4 and 24 h in the dose-response assay. Overall, our results indicate that the cell lines are moderately radioresistant, have a high repair capacity and behave similarly to a late-responding normal tissue. These findings indicate that the radiation protocols utilizing higher doses with less fractionation may be more effective for treating TCC.

  3. In vitro sublethal damage repair in tumour subpopulations from a heterogeneous human colon tumour

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    Leith, J.T.; Vayer, A.V. Jr.; DeWyngaert, J.K.; Amols, H.; Peck, R.A. Jr.; Glicksman, A.S. (Rhode Island Hospital (USA); Brown Univ., Providence, RI (USA))

    1984-01-01

    The repair of sublethal radiation damage in two asynchronously growing tumour cell subpopulations (clones A and D) obtained from a single human adenocarcinoma biopsy specimen has been studied. The survival data found after generation of complete survival curves from split dose experiments in which exposures were separated by 3, 6, 12, or 24 h were examined. It was found that the method of performing irradiations (e.g., suspension cultures versus monolayer cultures) affected the shape of the single dose response curves, and as a result the interpretation of the amount of sublethal damage repair occurring after split dose irradiation.

  4. Sublethal gamma irradiation affects reproductive impairment and elevates antioxidant enzyme and DNA repair activities in the monogonont rotifer Brachionus koreanus

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    Han, Jeonghoon; Won, Eun-Ji [Department of Biological Sciences, College of Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Kim, Il-Chan; Yim, Joung Han [Division of Life Sciences, Korea Polar Research Institute, Incheon 406-840 (Korea, Republic of); Lee, Su-Jae [Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Lee, Jae-Seong, E-mail: jslee2@skku.edu [Department of Biological Sciences, College of Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)

    2014-10-15

    Highlights: • No mortality within 96 h even at a high intensity (1200 Gy). • A reduced fecundity of Brachionus koreanus at over 150 Gy with a decrease in lifespan. • Dose-dependent ROS increase with GST enzyme activity at sub-lethal doses. • Significant impact on life table parameters, particularly fecundity. • Significant up-regulation of DNA repair-associated genes at sublethal doses. - Abstract: To examine the effects of gamma radiation on marine organisms, we irradiated several doses of gamma ray to the microzooplankton Brachionus koreanus, and measured in vivo and in vitro endpoints including the survival rate, lifespan, fecundity, population growth, gamma ray-induced oxidative stress, and modulated patterns of enzyme activities and gene expressions after DNA damage. After gamma radiation, no individuals showed any mortality within 96 h even at a high intensity (1200 Gy). However, a reduced fecundity (e.g. cumulated number of offspring) of B. koreanus at over 150 Gy was observed along with a slight decrease in lifespan. At 150 Gy and 200 Gy, the reduced fecundity of the rotifers led to a significant decrease in population growth, although in the second generation the population growth pattern was not affected even at 200 Gy when compared to the control group. At sub-lethal doses, reactive oxygen species (ROS) levels dose-dependently increased with GST enzyme activity. In addition, up-regulations of the antioxidant and chaperoning genes in response to gamma radiation were able to recover cellular damages, and life table parameters were significantly influenced, particularly with regard to fecundity. DNA repair-associated genes showed significantly up-regulated expression patterns in response to sublethal doses (150 and 200 Gy), as shown in the expression of the gamma-irradiated B. koreanus p53 gene, suggesting that these sublethal doses were not significantly fatal to B. koreanus but induced DNA damages leading to a decrease of the population size.

  5. DNA repair. [UV radiation

    Energy Technology Data Exchange (ETDEWEB)

    Setlow, R.

    1978-01-01

    Some topics discussed are as follows: difficulty in extrapolating data from E. coli to mammalian systems; mutations caused by UV-induced changes in DNA; mutants deficient in excision repair; other postreplication mechanisms; kinds of excision repair systems; detection of repair by biochemical or biophysical means; human mutants deficient in repair; mutagenic effects of UV on XP cells; and detection of UV-repair defects among XP individuals. (HLW)

  6. Sublethal effects of ultraviolet A radiation on Enterobacter cloacae.

    Science.gov (United States)

    Oppezzo, O J; Pizarro, R A

    2001-09-15

    We report the sublethal effects of ultraviolet A (UVA) on Enterobacter cloacae in comparison with those produced in Escherichia coli. UVA-induced sublethal effects were investigated in either bacterial membrane and at tRNA level. Limited dependence on oxygen concentration for photoinduced inhibition of biochemical membrane functions and low levels of oxidative damage during the irradiation period were found in En. cloacae. On the other hand, ultraviolet spectroscopy and reversed-phase HPLC analysis of hydrolysed tRNA showed that radio induced damage to tRNA is similar in En. cloacae and E. coli. Nevertheless, growth delay induced by UVA in En. cloacae was shorter than that found in E. coli submitted to the same experimental conditions. A limited post-irradiation ppGpp accumulation and the absence of any influence of the membrane damage on the growth delay extent seem to be responsible for the shortness of this effect in En. cloacae. Most of the differences between En. cloacae and E. coli could be attributed to an increased ability of En. cloacae to overcome oxidative stress during UVA exposure.

  7. Role of protein synthesis in the repair of sublethal x-ray damage in a mutant Chinese hamster ovary cell line

    Energy Technology Data Exchange (ETDEWEB)

    Yezzi, M.J.

    1985-04-01

    A temperature-sensitive mutant for protein synthesis, CHO-TSH1, has been compared to the wild-type cell, CHO-sC1, in single- and split-radiation-dose schemes. When the exponentially growing TS mutant and the wild-type cells were treated at 40/sub 0/C for up to 2 hrs prior to graded doses of x rays, the survival curves were identical and were the same as those obtained without heat treatment. If the cultures were incubated at 40/sup 0/C for 2 hrs before a first dose and maintained at 40/sup 0/C during a 2 hr dose fractionation interval, repair of radiation damage was reduced in the mutant compared to the wild type. These observations implied that a pool of proteins was involved in the repair of sublethal x-ray damage. However, if repair was measured by the alkaline-unwinding technique under the same time and temperature schemes, no difference in the kientics of DNA strand rejoining was observed. Misrepair processes may permit restoration of DNA strand integrity but not allow functional repair. The effect of diminished repair under conditions of inhibition of protein synthesis was found to be cell-cycle dependent in survival studies with synchronized mutant cell populations. Repair was found to be almost completely eliminated if the temperature sequence described above was applied in the middle of the DNA synthetic phase. Treatment of cell populations in the middle of G/sub 1/-phase yielded repair inhibition comparable to that observed with the asynchronous cells. Splitdose experiments were done using pre-incubation with cycloheximide to chemically inhibit protein synthesis. WT cells and TS cells were treated with cycloheximide at 35/sup 0/C for 2 hrs before a first dose and during a 2 hr dose fractionation interval. 23 figs., 7 tabs.

  8. Response to and recovery from acute sublethal gamma radiation in the Amazon molly, Poecilia formosa

    Energy Technology Data Exchange (ETDEWEB)

    Woodhead, A.D.; Setlow, R.B.

    1979-05-01

    Acute irradiation of the Amazon molly with a sublethal dose of 1,000 rad caused some damage to the intestinal tract and to the haematopoietic system. Histologically, the intestine appeared to have regenerated by the end of a week; damage to the haematopoietic tissue appeared more slowly, but repair was almost complete some two months later. Nevertheless, recovery to the intestine cannot have been entirely completed in seven days, since the fish did not feed well for the following two weeks. After this, there were no obvious deleterious effects upon the survival and viability of the fish, although irradiated fish weighed less at the termination of the experiment.

  9. The growth and development of Schistosoma mansoni in mice exposed to sublethal doses of radiation

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    Aitken, R.; Wilson, R.A. (Univ. of York, Heslington (England))

    1989-12-01

    The maturation of Schistosoma mansoni was studied in mice exposed to various sublethal doses of radiation. Although the treatment of mice with 500 rads of radiation prior to infection did not alter parasite maturation, doses in excess of 500 rads led to a reduction in worm burden. This could not be attributed to a delay in the arrival of parasites in the hepatic portal system. Worms developing in mice treated with 800 rads commenced egg-laying about 1 wk later than worms in intact mice, and the rate of egg deposition appeared to be lower in irradiated hosts. The data demonstrate that exposure of C57BL/6 mice to doses of radiation in excess of 500 rads impairs their ability to carry infections of S. mansoni. The findings do not support the hypothesis that primary worm burdens in the mouse are controlled by a host immune response.

  10. Dose-dependent hepatic transcriptional responses in Atlantic salmon (Salmo salar) exposed to sublethal doses of gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Song, You, E-mail: you.song@niva.no [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, N-0349 Oslo (Norway); Salbu, Brit; Teien, Hans-Christian; Heier, Lene Sørlie [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Rosseland, Bjørn Olav [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian University of Life Sciences (NMBU), Department of Ecology and Natural Resource Management, P.O. Box 5003, N-1432 Ås (Norway); Tollefsen, Knut Erik [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, N-0349 Oslo (Norway)

    2014-11-15

    affected DEGs associated with cellular signaling and immune response; 70 mGy radiation affected cell cycle regulation and DNA damage repair, cellular energy production; and 280 mGy radiation affected pathways related to cell cycle regulation and DNA repair, mitochondrial dysfunction and immune functions. Twelve genes representative of key pathways found in this study were verified by qPCR. Potential common MoAs of low-dose gamma radiation may include induction of oxidative stress, DNA damage and disturbance of oxidative phosphorylation (OXPHOS). Although common MoAs were proposed, a number of DEGs and pathways were still found to be dose-specific, potentially indicating multiple mechanisms of action (MOAs) of low-dose gamma radiation in fish. In addition, plasma glucose displayed an apparent increase with increasing radiation doses, although the results were not significantly different from the control. These findings suggested that sublethal doses of gamma radiation may cause dose-dependent transcriptional changes in the liver of Atlantic salmon after short-term exposure. The current study predicted multiple MoA for gamma radiation and may aid future impact assessment of environmental radioactivity in fish.

  11. Influence of UVB radiation on the lethal and sublethal toxicity of dispersed crude oil to planktonic copepod nauplii

    DEFF Research Database (Denmark)

    Almeda, Rodrigo; Harvey, Tracy E.; Connelly, Tara L

    2016-01-01

    Toxic effects of petroleum to marine zooplankton have been generally investigated using dissolved petroleum hydrocarbons and in the absence of sunlight. In this study, we determined the influence of natural ultraviolet B (UVB) radiation on the lethal and sublethal toxicity of dispersed crude oil...... in the sea after oil spills are highly toxic to copepod nauplii and that natural levels of UVB radiation substantially increase the toxicity of crude oil to these planktonic organisms. Overall, this study emphasizes the importance of considering sunlight in petroleum toxicological studies and models...

  12. Effect of sub-lethal exposure to ultraviolet radiation on the escape performance of Atlantic cod larvae (Gadus morhua.

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    Yuichi Fukunishi

    Full Text Available The amount of ultraviolet (UV radiation reaching the earth's surface has increased due to depletion of the ozone layer. Several studies have reported that UV radiation reduces survival of fish larvae. However, indirect and sub-lethal impacts of UV radiation on fish behavior have been given little consideration. We observed the escape performance of larval cod (24 dph, SL: 7.6±0.2 mm; 29 dph, SL: 8.2±0.3 mm that had been exposed to sub-lethal levels of UV radiation vs. unexposed controls. Two predators were used (in separate experiments: two-spotted goby (Gobiusculus flavescens; a suction predator and lion's mane jellyfish (Cyanea capillata; a "passive" ambush predator. Ten cod larvae were observed in the presence of a predator for 20 minutes using a digital video camera. Trials were replicated 4 times for goby and 5 times for jellyfish. Escape rate (total number of escapes/total number of attacks ×100, escape distance and the number of larvae remaining at the end of the experiment were measured. In the experiment with gobies, in the UV-treated larvae, both escape rate and escape distance (36%, 38±7.5 mm respectively were significantly lower than those of control larvae (75%, 69±4.7 mm respectively. There was a significant difference in survival as well (UV: 35%,63%. No apparent escape response was observed, and survival rate was not significantly different, between treatments (UV: 66%,74% in the experiment with jellyfish. We conclude that the effect and impact of exposure to sub-lethal levels of UV radiation on the escape performance of cod larvae depends on the type of predator. Our results also suggest that prediction of UV impacts on fish larvae based only on direct effects are underestimations.

  13. DNA repair and radiation sensitivity in mammalian cells

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    Chen, D.J.C.; Stackhouse, M. [Los Alamos National Lab., NM (United States); Chen, D.S. [Rochester Univ., NY (United States). Dept. of Radiation Oncology

    1993-02-01

    Ionizing radiation induces various types of damage in mammalian cells including DNA single-strand breaks, DNA double-strand breaks (DSB), DNA-protein cross links, and altered DNA bases. Although human cells can repair many of these lesions there is little detailed knowledge of the nature of the genes and the encoded enzymes that control these repair processes. We report here on the cellular and genetic analyses of DNA double-strand break repair deficient mammalian cells. It has been well established that the DNA double-strand break is one of the major lesions induced by ionizing radiation. Utilizing rodent repair-deficient mutant, we have shown that the genes responsible for DNA double-strand break repair are also responsible for the cellular expression of radiation sensitivity. The molecular genetic analysis of DSB repair in rodent/human hybrid cells indicate that at least 6 different genes in mammalian cells are responsible for the repair of radiation-induced DNA double-strand breaks. Mapping and the prospect of cloning of human radiation repair genes are reviewed. Understanding the molecular and genetic basis of radiation sensitivity and DNA repair in man will provide a rational foundation to predict the individual risk associated with radiation exposure and to prevent radiation-induced genetic damage in the human population.

  14. DNA repair and radiation sensitivity in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, D.J.C.; Stackhouse, M. (Los Alamos National Lab., NM (United States)); Chen, D.S. (Rochester Univ., NY (United States). Dept. of Radiation Oncology)

    1993-01-01

    Ionizing radiation induces various types of damage in mammalian cells including DNA single-strand breaks, DNA double-strand breaks (DSB), DNA-protein cross links, and altered DNA bases. Although human cells can repair many of these lesions there is little detailed knowledge of the nature of the genes and the encoded enzymes that control these repair processes. We report here on the cellular and genetic analyses of DNA double-strand break repair deficient mammalian cells. It has been well established that the DNA double-strand break is one of the major lesions induced by ionizing radiation. Utilizing rodent repair-deficient mutant, we have shown that the genes responsible for DNA double-strand break repair are also responsible for the cellular expression of radiation sensitivity. The molecular genetic analysis of DSB repair in rodent/human hybrid cells indicate that at least 6 different genes in mammalian cells are responsible for the repair of radiation-induced DNA double-strand breaks. Mapping and the prospect of cloning of human radiation repair genes are reviewed. Understanding the molecular and genetic basis of radiation sensitivity and DNA repair in man will provide a rational foundation to predict the individual risk associated with radiation exposure and to prevent radiation-induced genetic damage in the human population.

  15. UV Radiation Damage and Bacterial DNA Repair Systems

    Science.gov (United States)

    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…

  16. Chromosome aberrations and cellular premature senescence as radiation-induced sub-lethal effects: Implications for laser-driven charged-particle radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Manti, L.; Perozziello, F. M.; Grossi, G. [Department of Physical Sciences, University of Naples Federico II and INFN-Naples Section, Via Cintia, 80126 Naples (Italy)

    2013-07-26

    The use of charged particles significantly reduces the dose absorbed by normal cells due to the inverse dose-depth deposition profile. This is the physical pillar justifying hadrontherapy as the eligible treatment for deepseated tumours. However, a non-negligible amount of radiation is nevertheless absorbed in correspondence with the plateau region of the Bragg curve, which may result in the induction of sub-lethal effects. Very little experimental data exist on the induction of such effects. Moreover, reliable follow-up data on such adverse effects in hadrontherapy patients are limited since this type of treatment has been adopted relatively recently. A fortiori, the dependence of sub-lethal effects on unprecedented factors, such as the exceedingly high dose rates and/or the pulsed nature of beams originated by laser interaction with target materials, is unknown. This warrants investigation prior to a therapeutic use of such beams.

  17. Chromosome aberrations and cellular premature senescence as radiation-induced sub-lethal effects: Implications for laser-driven charged-particle radiotherapy

    Science.gov (United States)

    Manti, L.; Perozziello, F. M.; Grossi, G.

    2013-07-01

    The use of charged particles significantly reduces the dose absorbed by normal cells due to the inverse dose-depth deposition profile. This is the physical pillar justifying hadrontherapy as the eligible treatment for deepseated tumours. However, a non-negligible amount of radiation is nevertheless absorbed in correspondence with the plateau region of the Bragg curve, which may result in the induction of sub-lethal effects. Very little experimental data exist on the induction of such effects. Moreover, reliable follow-up data on such adverse effects in hadrontherapy patients are limited since this type of treatment has been adopted relatively recently. A fortiori, the dependence of sub-lethal effects on unprecedented factors, such as the exceedingly high dose rates and/or the pulsed nature of beams originated by laser interaction with target materials, is unknown. This warrants investigation prior to a therapeutic use of such beams.

  18. SIRT1 promotes DNA repair activity in response to radiation

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jae-Min; Lee, Kee-Ho [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2006-07-01

    Human SIRT1 controls various physiological responses including cell fate, stress, and aging, through deacetylation of its specific substrate protein. In processing DNA damage signaling, SIRT1 attenuates a cellular apoptotic response by deacetylation of p53 tumor suppressor. Ectopically over-expressed SIRT1 resulted in the increase of repair of DNA strand breakages produced by radiation. On the other hand, repression of endogenous SIRT1 expression by SIRT1 siRNA led to the decrease of this repair activity, indicating that SIRT1 can regulate DNA repair capacity of cells with DNA strand breaks.

  19. Countermeasure for Radiation Protection and Repair

    Science.gov (United States)

    2008-01-01

    Exposure to ionizing radiation during long-duration space missions is expected to cause short-term illness and increase long-term risk of cancer for astronauts. Radiation-induced free radicals overload the antioxidant defense mechanisms and lead to cellular damage at the membrane, enzyme, and chromosome levels. A large number of radioprotective agents were screened, but most had significant side effects. But there is increasing evidence that significant radioprotective benefit is achieved by increasing the dietary intake of foods with high antioxidant potential. Early plant-growing systems for space missions will be limited in both size and volume to minimize power and mass requirements. These systems will be well suited to producing plants containing high concentrations of bioprotective antioxidants. This project explored whether the production of bioprotective compounds could be increased by altering the lighting system, without increasing the space or power requirements for production, and evaluated the effects of environmental conditions (light quantity, light quality, and carbon dioxide [CO2] concentration) on the production of bioprotective compounds in lettuce, which provide a biological countermeasure for radiation exposure. The specific deliverables were to develop a database of bioprotectant compounds in plants that are suitable for use on longduration space missions, develop protocols for maintaining and increasing bioprotectant production under light emitting diodes (LEDs), recommend lighting requirements to produce dietary countermeasures of radiation, and publish results in the Journal of the American Society for Horticultural Science.

  20. The indirect effect of radiation reduces the repair fidelity of NHEJ as verified in repair deficient CHO cell lines exposed to different radiation qualities and potassium bromate

    Energy Technology Data Exchange (ETDEWEB)

    Bajinskis, Ainars, E-mail: ainars.bajinskis@gmt.su.se [Centre for Radiation Protection Research, Department of Genetics, Microbiology and Toxicology, Stockholm University, S-10691 Stockholm (Sweden); Olsson, Gunilla; Harms-Ringdahl, Mats [Centre for Radiation Protection Research, Department of Genetics, Microbiology and Toxicology, Stockholm University, S-10691 Stockholm (Sweden)

    2012-03-01

    The complexity of DNA lesions induced by ionizing radiation is mainly dependent on radiation quality, where the indirect action of radiation may contribute to different extent depending on the type of radiation under study. The effect of indirect action of radiation can be investigated by using agents that induce oxidative DNA damage or by applying free radical scavengers. The aim of this study was to investigate the role of the indirect effect of radiation for the repair fidelity of non-homologous end-joining (NHEJ), homologous recombination repair (HRR) and base excision repair (BER) when DNA damage of different complexity was induced by gamma radiation, alpha particles or from base damages (8-oxo-dG) induced by potassium bromate (KBrO{sub 3}). CHO cells lines deficient in XRCC3 (HRR) irs1SF, XRCC7 (NHEJ) V3-3 and XRCC1 (BER) EM9 were irradiated in the absence or presence of the free radical scavenger dimethyl sulfoxide (DMSO). The endpoints investigated included rate of cell proliferation by the DRAG assay, clonogenic cell survival and the level of primary DNA damage by the comet assay. The results revealed that the indirect effect of low-LET radiation significantly reduced the repair fidelity of both NHEJ and HRR pathways. For high-LET radiation the indirect effect of radiation also significantly reduced the repair fidelity for the repair deficient cell lines. The results suggest further that the repair fidelity of the error prone NHEJ repair pathway is more impaired by the indirect effect of high-LET radiation relative to the other repair pathways studied. The response to bromate observed for the two DSB repair deficient cell lines strongly support earlier studies that bromate induces complex DNA damages. The significantly reduced repair fidelity of irs1SF and V3-3 suggests that NHEJ as well as HRR are needed for the repair, and that complex DSBs are formed after bromate exposure.

  1. Suppressed expression of non-DSB repair genes inhibits gamma-radiation-induced cytogenetic repair and cell cycle arrest.

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H; Emami, Kamal; Hammond, Dianne; Casey, Rachael; Mehta, Satish K; Jeevarajan, Antony S; Pierson, Duane L; Wu, Honglu

    2008-11-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in double-strand break (DSB) repair, and its impact on cytogenetic responses has not been well studied. The purpose of this study is to identify new roles of IR inducible genes in regulating DSB repair and cell cycle progression. In this study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by small interfering RNA in human fibroblast cells. Frequency of micronuclei (MN) formation and chromosome aberrations were measured to determine efficiency of cytogenetic repair, especially DSB repair. In response to IR, the formation of MN was significantly increased by suppressed expression of five genes: Ku70 (DSB repair pathway), XPA (nucleotide excision repair pathway), RPA1 (mismatch repair pathway), RAD17 and RBBP8 (cell cycle control). Knocked-down expression of four genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Moreover, decreased XPA, p21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Nine of these eleven genes, whose knock-down expression affected cytogenetic repair, were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate IR-induced biological consequences. Furthermore, eight non-DBS repair genes showed involvement in regulating DSB repair, indicating that

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

    Energy Technology Data Exchange (ETDEWEB)

    Hartman, P.S.; Hevelone, J.; Dwarakanath, V.; Mitchell, D.L. (Texas Christian Univ., Fort Worth (USA))

    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). This 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.

  3. CXCL12 expression in hematopoietic tissues of mice exposed to sublethal dose of ionizing radiation in the presence od iNOS inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Perez Vieira, Daniel [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil). Lab. de Biologia Molecular; Hermida, Felipe Pessoa de Melo; Andrade Junior, Heitor Franco de [Instituto de Medicina Tropical de Sao Paulo, SP (Brazil). Lab. de Protozoologia

    2005-07-01

    their use associated to the CXCL12 chemokine to enhance the post-transplantation grafting of hematopoietic tissue and/or treatment of accidentally exposed individuals to sublethal doses of ionizing radiation. (author)

  4. Sublethal exposure to alpha radiation (223Ra dichloride) enhances various carcinomas' sensitivity to lysis by antigen-specific cytotoxic T lymphocytes through calreticulin-mediated immunogenic modulation.

    Science.gov (United States)

    Malamas, Anthony S; Gameiro, Sofia R; Knudson, Karin M; Hodge, James W

    2016-12-27

    Radium-223 dichloride (Xofigo®; 223Ra) is an alpha-emitting radiopharmaceutical FDA-approved for the treatment of bone metastases in patients with advanced castration-resistant prostate cancer. It is also being examined clinically in patients with breast and lung carcinoma and patients with multiple myeloma. As with other forms of radiation, the aim of 223Ra is to reduce tumor burden by directly killing tumor cells. External beam (photon) and proton radiation have been shown to augment tumor sensitivity to antigen-specific CD8+ cytotoxic T lymphocytes (CTLs). However, little is known about whether treatment with 223Ra can also induce such immunogenic modulation in tumor cells that survive irradiation. We examined these effects in vitro by exposing human prostate, breast, and lung carcinoma cells to sublethal doses of 223Ra. 223Ra significantly enhanced T cell-mediated lysis of each tumor type by CD8+ CTLs specific for MUC-1, brachyury, and CEA tumor antigens. Immunofluorescence analysis revealed that the increase in CTL killing was accompanied by augmented protein expression of MHC-I and calreticulin in each tumor type, molecules that are essential for efficient antigen presentation. Enhanced tumor-cell lysis was facilitated by calreticulin surface translocation following 223Ra exposure. The phenotypic changes observed after treatment appear to be mediated by induction of the endoplasmic reticulum stress response pathway. By rendering tumor cells more susceptible to T cell-mediated lysis, 223Ra may potentially be effective in combination with various immunotherapies, particularly cancer vaccines that are designed to generate and expand patients' endogenous antigen-specific T-cell populations against specific tumor antigens.

  5. DNA repair pathways in radiation induced cellular damage: a molecular approach

    NARCIS (Netherlands)

    L.R. van Veelen (Lieneke)

    2005-01-01

    markdownabstract__Abstract__ DNA damage, especially double-strand breaks, can be induced by endogenous or exogenous darnaging agents, such as ionizing radiation. Repair of DNA damage is very important in maintaining genomic stability. Incorrect repair may lead to chromosomal aberrations,

  6. DNA repair pathways in radiation induced cellular damage: a molecular approach

    NARCIS (Netherlands)

    L.R. van Veelen (Lieneke)

    2005-01-01

    markdownabstract__Abstract__ DNA damage, especially double-strand breaks, can be induced by endogenous or exogenous darnaging agents, such as ionizing radiation. Repair of DNA damage is very important in maintaining genomic stability. Incorrect repair may lead to chromosomal aberrations, translocat

  7. Perspectives in radiation biophysics: From radiation track structure simulation to mechanistic models of DNA damage and repair

    Science.gov (United States)

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

    2016-11-01

    In radiation targeted therapy and genetic risk estimation of low dose radiation protection there is a crucial need for full description of DNA damage response and repair (DDR) leading to cell death and cell mutation. We propose such a description can be arrived through realistic track-structure simulations together with mechanistic mathematical formulation of DDR and the availability of experimental data for testing the proof of principle. In this paper we review briefly first the state of the art in DNA damage and repair, and then the recent advances in the physics of track structure which represents an essential tool in radiation biophysics.

  8. Non-DBS DNA Repair Genes Regulate Radiation-induced Cytogenetic Damage Repair and Cell Cycle Progression

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Casey, Rachael; Wu, Honglu

    2008-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in DSB repair, and its impact on cytogenetic responses has not been systematically studied. In the present study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by transfection with small interfering RNA in human fibroblast cells. The purpose of this study is to identify new roles of these selected genes on regulating DSB repair and cell cycle progression , as measured in the micronuclei formation and chromosome aberration. In response to IR, the formation of MN was significantly increased by suppressed expression of 5 genes: Ku70 in the DSB repair pathway, XPA in the NER pathway, RPA1 in the MMR pathway, and RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, P21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Most of the 11 genes that affected cytogenetic responses are not known to have clear roles influencing DBS repair. Nine of these 11 genes were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate the biological consequences after IR.

  9. Non-DBS DNA Repair Genes Regulate Radiation-induced Cytogenetic Damage Repair and Cell Cycle Progression

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Casey, Rachael; Wu, Honglu

    2008-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in DSB repair, and its impact on cytogenetic responses has not been systematically studied. In the present study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by transfection with small interfering RNA in human fibroblast cells. The purpose of this study is to identify new roles of these selected genes on regulating DSB repair and cell cycle progression , as measured in the micronuclei formation and chromosome aberration. In response to IR, the formation of MN was significantly increased by suppressed expression of 5 genes: Ku70 in the DSB repair pathway, XPA in the NER pathway, RPA1 in the MMR pathway, and RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, P21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Most of the 11 genes that affected cytogenetic responses are not known to have clear roles influencing DBS repair. Nine of these 11 genes were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate the biological consequences after IR.

  10. Approach to the classical radiation biology. Ionizing radiation effects and repair mechanism of DNA double strand breaks

    Energy Technology Data Exchange (ETDEWEB)

    Utsumi, Hiroshi [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst

    2000-09-01

    Split-dose recovery has been observed under a variety of experimental conditions in many cell systems and believed to be the recovery of sublethal damage (SLD). It is considered to be one of the most widespread and important cellular responses in clinical radiotherapy. To study the molecular mechanism of this recovery, we analyzed the knockout mutants KU70{sup -/-}, RAD54{sup -/-}, and KU70{sup -/-}/ RAD54{sup -/-} of the chicken B-cell line, DT40. Rad54 participates in the homologous recombinational (HR) repair of DNA double-strand breaks (DSB), while Ku proteins are involved in non-homologous end-joining (NHEJ). Split-dose recovery was observed in the parent DT40 and KU70{sup -/-} cells. Moreover the split-dose survival enhancement had all of the characteristics of SLD recovery that had been demonstrated earlier: e.g., the reappearance of the shoulder of the survival curve with dose fractionation; repair at 25degC; and inhibition by the antibiotic actinomycin D. These results strongly suggest that SLD recovery is due to DSB repair via or mediated by HR, and that these breaks constitute SLD. The tonicity-sensitive potentially lethal damage (PLD) recovery was also found only in DT40 and KU70 {sup -/-} cells. Delayed-plating PLD recovery may be controlled by NHEJ repair that works through the cell cycle. These results lead to the conclusion that the repair of DSBs could explain the classical operational recovery phenomena. We have also investigated RBE/LET using those mutants. (author)

  11. Radiation- and drug-induced DNA repair in mammalian oocytes and embryos

    Energy Technology Data Exchange (ETDEWEB)

    Pedersen, R A; Brandriff, B

    1979-01-01

    A review of studies showing ultraviolet- or drug-induced unscheduled DNA synthesis in mammalian oocytes and embryos suggests that the female gamete has an excision repair capacity from the earliest stages of oocyte growth. The oocyte's demonstrable excision repair capacity decreases at the time of meiotic maturation for unknown reasons, but the fully mature oocyte maintans a repair capacity, in contrast to the mature sperm, and contributes this to the zygote. Early embryo cells maintain relatively constant levels of excision repair until late fetal stages, when they lose their capacity for excision repair. These apparent changes in excision repair capacity do not have a simple relationship to known differences in radiation sensitivity of germ cells and embryos.

  12. DNA repair gene polymorphisms in relation to chromosome aberration frequencies in retired radiation workers

    Energy Technology Data Exchange (ETDEWEB)

    Wilding, Craig S. [Genetics Department, Westlakes Research Institute, Westlakes Science and Technology Park, Moor Row, Cumbria CA24 3JY (United Kingdom)]. E-mail: craig.wilding@westlakes.ac.uk; Relton, Caroline L. [Genetics Department, Westlakes Research Institute, Westlakes Science and Technology Park, Moor Row, Cumbria CA24 3JY (United Kingdom); Paediatric and Lifecourse Epidemiology Research Group, School of Clinical Medical Sciences (Child Health), Newcastle University, Sir James Spence Institute, Royal Victoria Infirmary, Newcastle-upon-Tyne NE1 4LP (United Kingdom); Rees, Gwen S. [Genetics Department, Westlakes Research Institute, Westlakes Science and Technology Park, Moor Row, Cumbria CA24 3JY (United Kingdom); Tarone, Robert E. [International Epidemiology Institute, 1455 Research Boulevard, Suite 550, Rockville, MD 20850 (United States); Whitehouse, Caroline A. [Genetics Department, Westlakes Research Institute, Westlakes Science and Technology Park, Moor Row, Cumbria CA24 3JY (United Kingdom); Tawn, E. Janet [Genetics Department, Westlakes Research Institute, Westlakes Science and Technology Park, Moor Row, Cumbria CA24 3JY (United Kingdom)

    2005-02-15

    Polymorphic variation in DNA repair genes was examined in a group of retired workers from the British Nuclear Fuels plc facility at Sellafield in relation to previously determined translocation frequencies in peripheral blood lymphocytes. Variation at seven polymorphisms in four genes involved in the base excision repair (XRCC1 R194W, R399Q and a [AC]{sub n} microsatellite in the 3' UTR) and double strand break repair (XRCC3 T241M and a [AC]{sub n} microsatellite in intron 3 of XRCC3, XRCC4 I134T, and a GACTAn microsatellite located 120kb 5' of XRCC5) pathways was determined for 291 retired radiation workers who had received cumulative occupational external radiation doses of between 0 and 1873mSv. When the interaction between radiation dose and each DNA repair gene polymorphism was examined in relation to translocation frequency there was no evidence for any of the polymorphisms studied influencing the response to occupational exposure. A positive interaction observed between genotype (individuals with at least one allele >=20 repeat units) at a microsatellite locus in the XRCC3 gene and smoking status should be interpreted cautiously because interactions were investigated for seven polymorphisms and two exposures. Nonetheless, further research is warranted to examine whether this DNA repair gene variant might be associated with a sub-optimal repair response to smoking-induced DNA damage and hence an increased frequency of translocations.

  13. DNA repair and cell cycle biomarkers of radiation exposure and inflammation stress in human blood.

    Directory of Open Access Journals (Sweden)

    Helen Budworth

    Full Text Available DNA damage and repair are hallmarks of cellular responses to ionizing radiation. We hypothesized that monitoring the expression of DNA repair-associated genes would enhance the detection of individuals exposed to radiation versus other forms of physiological stress. We employed the human blood ex vivo radiation model to investigate the expression responses of DNA repair genes in repeated blood samples from healthy, non-smoking men and women exposed to 2 Gy of X-rays in the context of inflammation stress mimicked by the bacterial endotoxin lipopolysaccharide (LPS. Radiation exposure significantly modulated the transcript expression of 12 genes of 40 tested (2.2E-06radiation. Three genes of this panel (CDKN1A, FDXR and BBC3 were also highly sensitive to LPS treatment in the absence of radiation exposure, and LPS co-treatment significantly affected their radiation responses. At the protein level, BAX and pCHK2-thr68 were elevated after radiation exposure, but the pCHK2-thr68 response was significantly decreased in the presence of LPS. Our combined panel yields an estimated 4-group accuracy of ∼90% to discriminate between radiation alone, inflammation alone, or combined exposures. Our findings suggest that DNA repair gene expression may be helpful to identify biodosimeters of exposure to radiation, especially within high-complexity exposure scenarios.

  14. Molecular Mechanisms of Ultraviolet Radiation-Induced DNA Damage and Repair

    Directory of Open Access Journals (Sweden)

    Rajesh P. Rastogi

    2010-01-01

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

  15. Induction of DNA repair synthesis by ultraviolet radiation and methylmethanesulphonate in cultured mouse lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, V.; Zantedeschi, A.; Levis, A.G. (Padua Univ. (Italy). Ist. di Zoologia e Anatomia Comparata); Ronchese, F. (Inst. of Pathological Anatomy, Padua (Italy))

    1983-02-01

    The induction of DNA repair synthesis by UV-radiation and methylmethanesulphonate (MMS) was studied in mouse lymphocytes and leukemic cells by means of autoradiography and scintillation counting, after labelling in vitro with tritiated thymidine ((/sup 3/H)dThd). Repair stimulation was detected by both procedures in LSTRA AND YC8 leukemic cell lines as well as in primary fibroblasts of BALB/c and BALB/Mo mice. No stimulation was observed in primary cultures of lymphocytes from the spleen, thymus and lymph-nodes of the same mice. In primary lymphocytes neither stimulation with concanavalin A (Con A) nor pre-incubation with 5-bromodeoxyuridine (BUdR) were effective in making evident DNA repair. The data put into question the reliability of the repair test for the prediction of carcinogenic potential of chemicals.

  16. Influence of XRCC1 Genetic Polymorphisms on Ionizing Radiation-Induced DNA Damage and Repair

    Science.gov (United States)

    Sterpone, Silvia; Cozzi, Renata

    2010-01-01

    It is well known that ionizing radiation (IR) can damage DNA through a direct action, producing single- and double-strand breaks on DNA double helix, as well as an indirect effect by generating oxygen reactive species in the cells. Mammals have evolved several and distinct DNA repair pathways in order to maintain genomic stability and avoid tumour cell transformation. This review reports important data showing a huge interindividual variability on sensitivity to IR and in susceptibility to developing cancer; this variability is principally represented by genetic polymorphisms, that is, DNA repair gene polymorphisms. In particular we have focussed on single nucleotide polymorphisms (SNPs) of XRCC1, a gene that encodes for a scaffold protein involved basically in Base Excision Repair (BER). In this paper we have reported and presented recent studies that show an influence of XRCC1 variants on DNA repair capacity and susceptibility to breast cancer. PMID:20798883

  17. Influence of XRCC1 Genetic Polymorphisms on Ionizing Radiation-Induced DNA Damage and Repair

    Directory of Open Access Journals (Sweden)

    Silvia Sterpone

    2010-01-01

    Full Text Available It is well known that ionizing radiation (IR can damage DNA through a direct action, producing single- and double-strand breaks on DNA double helix, as well as an indirect effect by generating oxygen reactive species in the cells. Mammals have evolved several and distinct DNA repair pathways in order to maintain genomic stability and avoid tumour cell transformation. This review reports important data showing a huge interindividual variability on sensitivity to IR and in susceptibility to developing cancer; this variability is principally represented by genetic polymorphisms, that is, DNA repair gene polymorphisms. In particular we have focussed on single nucleotide polymorphisms (SNPs of XRCC1, a gene that encodes for a scaffold protein involved basically in Base Excision Repair (BER. In this paper we have reported and presented recent studies that show an influence of XRCC1 variants on DNA repair capacity and susceptibility to breast cancer.

  18. Modeling of DSBs Generation and Repair Process under Ion Radiation

    Institute of Scientific and Technical Information of China (English)

    QI Jin-peng; SHAO Shi-huang; XIE Jin-li; BAI Hui

    2007-01-01

    Under acute perturbations from outside, cell can trigger the self-defense mechanisms in fighting against these genome stresses. To simulate the investigation of the complicated mechanisms of cellular responding DNA damage at single cell level, a model of the double strand breaks (DSBs) generation and repair process is proposed under continuous effect of acute IR. Under different IR dose domains, this model can be used to simulate the complicated interactions among vital components within the cell, and the plausible outcomes of cellular response in fighting against DNA damage.

  19. Repair-dependent cell radiation survival and transformation: an integrated theory.

    Science.gov (United States)

    Sutherland, John C

    2014-09-07

    The repair-dependent model of cell radiation survival is extended to include radiation-induced transformations. The probability of transformation is presumed to scale with the number of potentially lethal damages that are repaired in a surviving cell or the interactions of such damages. The theory predicts that at doses corresponding to high survival, the transformation frequency is the sum of simple polynomial functions of dose; linear, quadratic, etc, essentially as described in widely used linear-quadratic expressions. At high doses, corresponding to low survival, the ratio of transformed to surviving cells asymptotically approaches an upper limit. The low dose fundamental- and high dose plateau domains are separated by a downwardly concave transition region. Published transformation data for mammalian cells show the high-dose plateaus predicted by the repair-dependent model for both ultraviolet and ionizing radiation. For the neoplastic transformation experiments that were analyzed, the data can be fit with only the repair-dependent quadratic function. At low doses, the transformation frequency is strictly quadratic, but becomes sigmodial over a wider range of doses. Inclusion of data from the transition region in a traditional linear-quadratic analysis of neoplastic transformation frequency data can exaggerate the magnitude of, or create the appearance of, a linear component. Quantitative analysis of survival and transformation data shows good agreement for ultraviolet radiation; the shapes of the transformation components can be predicted from survival data. For ionizing radiations, both neutrons and x-rays, survival data overestimate the transforming ability for low to moderate doses. The presumed cause of this difference is that, unlike UV photons, a single x-ray or neutron may generate more than one lethal damage in a cell, so the distribution of such damages in the population is not accurately described by Poisson statistics. However, the complete

  20. Nonhomologous end-joining repair plays a more important role than homologous recombination repair in defining radiosensitivity after exposure to high-LET radiation.

    Science.gov (United States)

    Takahashi, Akihisa; Kubo, Makoto; Ma, Hongyu; Nakagawa, Akiko; Yoshida, Yukari; Isono, Mayu; Kanai, Tatsuaki; Ohno, Tatsuya; Furusawa, Yoshiya; Funayama, Tomoo; Kobayashi, Yasuhiko; Nakano, Takashi

    2014-09-01

    DNA double-strand breaks (DSBs) induced by ionizing radiation pose a major threat to cell survival. The cell can respond to the presence of DSBs through two major repair pathways: homologous recombination (HR) and nonhomologous end joining (NHEJ). Higher levels of cell death are induced by high-linear energy transfer (LET) radiation when compared to low-LET radiation, even at the same physical doses, due to less effective and efficient DNA repair. To clarify whether high-LET radiation inhibits all repair pathways or specifically one repair pathway, studies were designed to examine the effects of radiation with different LET values on DNA DSB repair and radiosensitivity. Embryonic fibroblasts bearing repair gene (NHEJ-related Lig4 and/or HR-related Rad54) knockouts (KO) were used and their responses were compared to wild-type cells. The cells were exposed to X rays, spread-out Bragg peak (SOBP) carbon ion beams as well as with carbon, iron, neon and argon ions. Cell survival was measured with colony-forming assays. The sensitization enhancement ratio (SER) values were calculated using the 10% survival dose of wild-type cells and repair-deficient cells. Cellular radiosensitivity was listed in descending order: double-KO cells > Lig4-KO cells > Rad54-KO cells > wild-type cells. Although Rad54-KO cells had an almost constant SER value, Lig4-KO cells showed a high-SER value when compared to Rad54-KO cells, even with increasing LET values. These results suggest that with carbon-ion therapy, targeting NHEJ repair yields higher radiosensitivity than targeting homologous recombination repair.

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

    Directory of Open Access Journals (Sweden)

    Daniel L. Jones

    2017-09-01

    Full Text Available 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.

  2. Suppression of DNA-dependent protein kinase sensitize cells to radiation without affecting DSB repair.

    Science.gov (United States)

    Gustafsson, Ann-Sofie; Abramenkovs, Andris; Stenerlöw, Bo

    2014-11-01

    Efficient and correct repair of DNA double-strand break (DSB) is critical for cell survival. Defects in the DNA repair may lead to cell death, genomic instability and development of cancer. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is an essential component of the non-homologous end joining (NHEJ) which is the major DSB repair pathway in mammalian cells. In the present study, by using siRNA against DNA-PKcs in four human cell lines, we examined how low levels of DNA-PKcs affected cellular response to ionizing radiation. Decrease of DNA-PKcs levels by 80-95%, induced by siRNA treatment, lead to extreme radiosensitivity, similar to that seen in cells completely lacking DNA-PKcs and low levels of DNA-PKcs promoted cell accumulation in G2/M phase after irradiation and blocked progression of mitosis. Surprisingly, low levels of DNA-PKcs did not affect the repair capacity and the removal of 53BP1 or γ-H2AX foci and rejoining of DSB appeared normal. This was in strong contrast to cells completely lacking DNA-PKcs and cells treated with the DNA-PKcs inhibitor NU7441, in which DSB repair were severely compromised. This suggests that there are different mechanisms by which loss of DNA-PKcs functions can sensitize cells to ionizing radiation. Further, foci of phosphorylated DNA-PKcs (T2609 and S2056) co-localized with DSB and this was independent of the amount of DNA-PKcs but foci of DNA-PKcs was only seen in siRNA-treated cells. Our study emphasizes on the critical role of DNA-PKcs for maintaining survival after radiation exposure which is uncoupled from its essential function in DSB repair. This could have implications for the development of therapeutic strategies aiming to radiosensitize tumors by affecting the DNA-PKcs function.

  3. Repair of radiation-induced DNA double-strand breaks in isolated nuclei of Physarum polycephalum

    Energy Technology Data Exchange (ETDEWEB)

    Brewer, E.N.

    1979-08-01

    Radiation-induced DNA double-strand breaks are rejoined in homogenates and isolated nuclei of Physarum polycephalum. In agreement with results obtained previously for intact plasmodia, double-strand breaks are less extensively repaired in nuclei isolated from S-phase, as compared to G/sub 2/-phase, cultures. A corresponding propensity of DNA present in unirradiated nuclei of S-phase plasmodia toward breakage during incubation in vitro was observed. Repair of putative single-strand breaks, as ascertained from alkaline sucrose density-gradient centrifugation analysis, was not observed. The possible relationships between these phenomena are discussed.

  4. Effect of fractionation and rate of radiation dose on human leukemic cells, HL-60

    Energy Technology Data Exchange (ETDEWEB)

    Rhee, J.G.; Song, C.W.; Kim, T.H.; Levitt, S.H.

    1985-03-01

    The capacity of HL-60 cells, human acute promyelocytic leukemic cells established in culture, to repair sublethal radiation damage was estimated from the response of the cells to fractionated irradiation or to a single irradiation at difference dose rates. After exposure of cells to a single dose of X rays at a dose rate of 78 rad/min, the survival curve was characterized by n = 2.5, D/sub q/ = 80 rad, and D/sub 0/ = 83.2 rad. Split-dose studies demonstrated that the cells were able to repair a substantial portion of sublethal radiation damage in 2 hr. The response of the cells to irradiation at different dose rates decreased with a decrease in the dose rates, which could be attributed to repair of sublethal radiation damage. The possibility that some of the malignant hemopoietic cells, if not all, may possess a substantial capacity to repair sublethal radiation damage should not be underestimated in planning total-body irradiation followed by bone marrow transplantation.

  5. Bridging Plant and Human Radiation Response and DNA Repair through an In Silico Approach

    Directory of Open Access Journals (Sweden)

    Zacharenia Nikitaki

    2017-06-01

    Full Text Available The mechanisms of response to radiation exposure are conserved in plants and animals. The DNA damage response (DDR pathways are the predominant molecular pathways activated upon exposure to radiation, both in plants and animals. The conserved features of DDR in plants and animals might facilitate interdisciplinary studies that cross traditional boundaries between animal and plant biology in order to expand the collection of biomarkers currently used for radiation exposure monitoring (REM in environmental and biomedical settings. Genes implicated in trans-kingdom conserved DDR networks often triggered by ionizing radiation (IR and UV light are deposited into biological databases. In this study, we have applied an innovative approach utilizing data pertinent to plant and human genes from publicly available databases towards the design of a ‘plant radiation biodosimeter’, that is, a plant and DDR gene-based platform that could serve as a REM reliable biomarker for assessing environmental radiation exposure and associated risk. From our analysis, in addition to REM biomarkers, a significant number of genes, both in human and Arabidopsis thaliana, not yet characterized as DDR, are suggested as possible DNA repair players. Last but not least, we provide an example on the applicability of an Arabidopsis thaliana—based plant system monitoring the role of cancer-related DNA repair genes BRCA1, BARD1 and PARP1 in processing DNA lesions.

  6. Nrf2 facilitates repair of radiation induced DNA damage through homologous recombination repair pathway in a ROS independent manner in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Jayakumar, Sundarraj; Pal, Debojyoti; Sandur, Santosh K., E-mail: sskumar@barc.gov.in

    2015-09-15

    Highlights: • Nrf2 inhibition in A549 cells led to attenuated DNA repair and radiosensitization. • Influence of Nrf2 on DNA repair is not linked to its antioxidant function. • Nrf2 influences DNA repair through homologous recombination (HR) repair pathway. • Many genes involved in HR pathway show ARE sequences in their upstream region. - Abstract: Nrf2 is a redox sensitive transcription factor that is involved in the co-ordinated transcription of genes involved in redox homeostasis. But the role of Nrf2 in DNA repair is not investigated in detail. We have employed A549 and MCF7 cells to study the role of Nrf2 on DNA repair by inhibiting Nrf2 using all-trans retinoic acid (ATRA) or by knock down approach prior to radiation exposure (4 Gy). DNA damage and repair analysis was studied by γH2AX foci formation and comet assay. Results suggested that the inhibition of Nrf2 in A549 or MCF7 cells led to significant slowdown in DNA repair as compared to respective radiation controls. The persistence of residual DNA damage even in the presence of free radical scavenger N-acetyl cysteine, suggested that the influence of Nrf2 on DNA repair was not linked to its antioxidant functions. Further, its influence on non-homologous end joining repair pathway was studied by inhibiting both Nrf2 and DNA-PK together. This led to synergistic reduction of survival fraction, indicating that Nrf2 may not be influencing the NHEJ pathway. To investigate the role of homologous recombination repair (HR) pathway, RAD51 foci formation was monitored. There was a significant reduction in the foci formation in cells treated with ATRA or shRNA against Nrf2 as compared to their respective radiation controls. Further, Nrf2 inhibition led to significant reduction in mRNA levels of RAD51. BLAST analysis was also performed on upstream regions of DNA repair genes to identify antioxidant response element and found that many repair genes that are involved in HR pathway may be regulated by Nrf2

  7. Suppression of DNA-dependent protein kinase sensitize cells to radiation without affecting DSB repair

    Energy Technology Data Exchange (ETDEWEB)

    Gustafsson, Ann-Sofie, E-mail: ann-sofie.gustafsson@bms.uu.se; Abramenkovs, Andris; Stenerlöw, Bo

    2014-11-15

    Highlights: • We reduced the level of DNA-PKcs with siRNA and examined cells after γ-irradiation. • Low DNA-PKcs levels lead to radiosensitivity but did not affect repair of DSB. • Low DNA-PKcs levels may block progression of mitosis. • DNA-PKcs role in mitotic progression is independent of its role in DSB repair. • We suggest different mechanisms by which loss of DNA-PKcs function sensitize cells. - Abstract: Efficient and correct repair of DNA double-strand break (DSB) is critical for cell survival. Defects in the DNA repair may lead to cell death, genomic instability and development of cancer. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is an essential component of the non-homologous end joining (NHEJ) which is the major DSB repair pathway in mammalian cells. In the present study, by using siRNA against DNA-PKcs in four human cell lines, we examined how low levels of DNA-PKcs affected cellular response to ionizing radiation. Decrease of DNA-PKcs levels by 80–95%, induced by siRNA treatment, lead to extreme radiosensitivity, similar to that seen in cells completely lacking DNA-PKcs and low levels of DNA-PKcs promoted cell accumulation in G2/M phase after irradiation and blocked progression of mitosis. Surprisingly, low levels of DNA-PKcs did not affect the repair capacity and the removal of 53BP1 or γ-H2AX foci and rejoining of DSB appeared normal. This was in strong contrast to cells completely lacking DNA-PKcs and cells treated with the DNA-PKcs inhibitor NU7441, in which DSB repair were severely compromised. This suggests that there are different mechanisms by which loss of DNA-PKcs functions can sensitize cells to ionizing radiation. Further, foci of phosphorylated DNA-PKcs (T2609 and S2056) co-localized with DSB and this was independent of the amount of DNA-PKcs but foci of DNA-PKcs was only seen in siRNA-treated cells. Our study emphasizes on the critical role of DNA-PKcs for maintaining survival after radiation exposure

  8. DNA damage and repair in plants under ultraviolet and ionizing radiations.

    Science.gov (United States)

    Gill, Sarvajeet S; Anjum, Naser A; Gill, Ritu; Jha, Manoranjan; Tuteja, Narendra

    2015-01-01

    Being sessile, plants are continuously exposed to DNA-damaging agents present in the environment such as ultraviolet (UV) and ionizing radiations (IR). Sunlight acts as an energy source for photosynthetic plants; hence, avoidance of UV radiations (namely, UV-A, 315-400 nm; UV-B, 280-315 nm; and UV-C, exposure, plants make use of several DNA repair mechanisms. In the light of recent breakthrough, the current minireview (a) introduces UV/IR and overviews UV/IR-mediated DNA damage products and (b) critically discusses the biochemistry and genetics of major pathways responsible for the repair of UV/IR-accrued DNA damage. The outcome of the discussion may be helpful in devising future research in the current context.

  9. Inhibition of non-homologous end joining repair impairs pancreatic cancer growth and enhances radiation response.

    Directory of Open Access Journals (Sweden)

    Ying-Hua Li

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is amongst the deadliest of human cancers, due to its late diagnosis as well as its intense resistance to currently available therapeutics. To identify mechanisms as to why PDAC are refractory to DNA damaging cytoxic chemotherapy and radiation, we performed a global interrogation of the DNA damage response of PDAC. We find that PDAC cells generally harbor high levels of spontaneous DNA damage. Inhibition of Non-Homologous End Joining (NHEJ repair either pharmacologically or by RNAi resulted in a further accumulation of DNA damage, inhibition of growth, and ultimately apoptosis even in the absence of exogenous DNA damaging agents. In response to radiation, PDAC cells rely on the NHEJ pathway to rapidly repair DNA double strand breaks. Mechanistically, when NHEJ is inhibited there is a compensatory increase in Homologous Recombination (HR. Despite this upregulation of HR, DNA damage persists and cells are significantly more sensitive to radiation. Together, these findings support the incorporation of NHEJ inhibition into PDAC therapeutic approaches, either alone, or in combination with DNA damaging therapies such as radiation.

  10. Reduced Activity of Double-Strand Break Repair Genes in Prostate Cancer Patients With Late Normal Tissue Radiation Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Oorschot, Bregje van, E-mail: b.vanoorschot@amc.uva.nl [Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Hovingh, Suzanne E. [Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Moerland, Perry D. [Bioinformatics Laboratory, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Medema, Jan Paul; Stalpers, Lukas J.A. [Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Vrieling, Harry [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Franken, Nicolaas A.P. [Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands)

    2014-03-01

    Purpose: To investigate clinical parameters and DNA damage response as possible risk factors for radiation toxicity in the setting of prostate cancer. Methods and Materials: Clinical parameters of 61 prostate cancer patients, 34 with (overresponding, OR) and 27 without (non-responding, NR) severe late radiation toxicity were assembled. In addition, for a matched subset the DNA damage repair kinetics (γ-H2AX assay) and expression profiles of DNA repair genes were determined in ex vivo irradiated lymphocytes. Results: Examination of clinical data indicated none of the considered clinical parameters to be correlated with the susceptibility of patients to develop late radiation toxicity. Although frequencies of γ-H2AX foci induced immediately after irradiation were similar (P=.32), significantly higher numbers of γ-H2AX foci were found 24 hours after irradiation in OR compared with NR patients (P=.03). Patient-specific γ-H2AX foci decay ratios were significantly higher in NR patients than in OR patients (P<.0001). Consequently, NR patients seem to repair DNA double-strand breaks (DSBs) more efficiently than OR patients. Moreover, gene expression analysis indicated several genes of the homologous recombination pathway to be stronger induced in NR compared with OR patients (P<.05). A similar trend was observed in genes of the nonhomologous end-joining repair pathway (P=.09). This is congruent with more proficient repair of DNA DSBs in patients without late radiation toxicity. Conclusions: Both gene expression profiling and DNA DSB repair kinetics data imply that less-efficient repair of radiation-induced DSBs may contribute to the development of late normal tissue damage. Induction levels of DSB repair genes (eg, RAD51) may potentially be used to assess the risk for late radiation toxicity.

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Eccles, Laura J., E-mail: laura.eccles@rob.ox.ac.uk [DNA Damage Group, Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ (United Kingdom); O' Neill, Peter, E-mail: peter.oneill@rob.ox.ac.uk [DNA Damage Group, Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ (United Kingdom); Lomax, Martine E., E-mail: martine.lomax@rob.ox.ac.uk [DNA Damage Group, Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ (United Kingdom)

    2011-06-03

    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.

  13. Mechanistic Modelling of DNA Repair and Cellular Survival Following Radiation-Induced DNA Damage

    Science.gov (United States)

    McMahon, Stephen J.; Schuemann, Jan; Paganetti, Harald; Prise, Kevin M.

    2016-09-01

    Characterising and predicting the effects of ionising radiation on cells remains challenging, with the lack of robust models of the underlying mechanism of radiation responses providing a significant limitation to the development of personalised radiotherapy. In this paper we present a mechanistic model of cellular response to radiation that incorporates the kinetics of different DNA repair processes, the spatial distribution of double strand breaks and the resulting probability and severity of misrepair. This model enables predictions to be made of a range of key biological endpoints (DNA repair kinetics, chromosome aberration and mutation formation, survival) across a range of cell types based on a set of 11 mechanistic fitting parameters that are common across all cells. Applying this model to cellular survival showed its capacity to stratify the radiosensitivity of cells based on aspects of their phenotype and experimental conditions such as cell cycle phase and plating delay (correlation between modelled and observed Mean Inactivation Doses R2 > 0.9). By explicitly incorporating underlying mechanistic factors, this model can integrate knowledge from a wide range of biological studies to provide robust predictions and may act as a foundation for future calculations of individualised radiosensitivity.

  14. Cytogenetic Response to Ionizing Radiation Exposure in Human Fibroblasts with Suppressed Expression of Non-DSB Repair Genes

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Hammond, Dianne; Mehta, Satish K.; Jeevarajan, Antony S.; Pierson, Duane L.; Wu, Honglu

    2009-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in double-strand break (DSB) repair, and its impact on cytogenetic responses has not been well studied. The purpose of this study is to identify new roles of IR inducible genes in radiation-induced chromosome aberrations and micronuclei formation. In the study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by small interfering RNA in human fibroblast cells. Frequencies of micronuclei (MN) formation and chromosome aberrations were measured to determine the efficiency of cytogenetic repair, and the fraction of bi-nucleated cells in the MN analysis was used as a marker for cell cycle progression. In response to gamma radiation, the formation of MN was significantly increased by suppressed expression of five genes: Ku70 (DSB repair pathway), XPA (nucleotide excision repair pathway), RPA1 (mismatch repair pathway), RAD17 and RBBP8 (cell cycle control). Knocked-down expression of four genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Moreover, decreased XPA, p21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Nine of these eleven genes, whose knock-down expression affected cytogenetic repair, were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate IR

  15. Cytogenetic Response to Ionizing Radiation Exposure in Human Fibroblasts with Suppressed Expression of Non-DSB Repair Genes

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Hammond, Dianne; Mehta, Satish K.; Jeevarajan, Antony S.; Pierson, Duane L.; Wu, Honglu

    2009-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in double-strand break (DSB) repair, and its impact on cytogenetic responses has not been well studied. The purpose of this study is to identify new roles of IR inducible genes in radiation-induced chromosome aberrations and micronuclei formation. In the study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by small interfering RNA in human fibroblast cells. Frequencies of micronuclei (MN) formation and chromosome aberrations were measured to determine the efficiency of cytogenetic repair, and the fraction of bi-nucleated cells in the MN analysis was used as a marker for cell cycle progression. In response to gamma radiation, the formation of MN was significantly increased by suppressed expression of five genes: Ku70 (DSB repair pathway), XPA (nucleotide excision repair pathway), RPA1 (mismatch repair pathway), RAD17 and RBBP8 (cell cycle control). Knocked-down expression of four genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Moreover, decreased XPA, p21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Nine of these eleven genes, whose knock-down expression affected cytogenetic repair, were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate IR

  16. Skin-resident T cells sense ultraviolet radiation-induced injury and contribute to DNA repair.

    Science.gov (United States)

    MacLeod, Amanda S; Rudolph, Ross; Corriden, Ross; Ye, Ivan; Garijo, Olivia; Havran, Wendy L

    2014-06-15

    Skin-resident T cells have been shown to play important roles in tissue homeostasis and wound repair, but their role in UV radiation (UVR)-mediated skin injury and subsequent tissue regeneration is less clear. In this study, we demonstrate that acute UVR rapidly activates skin-resident T cells in humans and dendritic epidermal γδ T cells (DETCs) in mice through mechanisms involving the release of ATP from keratinocytes. Following UVR, extracellular ATP leads to an increase in CD69 expression, proliferation, and IL-17 production, and to changes in DETC morphology. Furthermore, we find that the purinergic receptor P2X7 and caspase-1 are necessary for UVR-induced IL-1 production in keratinocytes, which increases IL-17 secretion by DETCs. IL-17, in turn, induces epidermal TNF-related weak inducer of apoptosis and growth arrest and DNA damage-associated gene 45, two molecules linked to the DNA repair response. Finally, we demonstrate that DETCs and human skin-resident T cells limit DNA damage in keratinocytes. Taken together, our findings establish a novel role for skin-resident T cells in the UVR-associated DNA repair response and underscore the importance of skin-resident T cells to overall skin regeneration.

  17. DNA Damage and Repair in Plants under Ultraviolet and Ionizing Radiations

    Directory of Open Access Journals (Sweden)

    Sarvajeet S. Gill

    2015-01-01

    Full Text Available Being sessile, plants are continuously exposed to DNA-damaging agents present in the environment such as ultraviolet (UV and ionizing radiations (IR. Sunlight acts as an energy source for photosynthetic plants; hence, avoidance of UV radiations (namely, UV-A, 315–400 nm; UV-B, 280–315 nm; and UV-C, <280 nm is unpreventable. DNA in particular strongly absorbs UV-B; therefore, it is the most important target for UV-B induced damage. On the other hand, IR causes water radiolysis, which generates highly reactive hydroxyl radicals (OH• and causes radiogenic damage to important cellular components. However, to maintain genomic integrity under UV/IR exposure, plants make use of several DNA repair mechanisms. In the light of recent breakthrough, the current minireview (a introduces UV/IR and overviews UV/IR-mediated DNA damage products and (b critically discusses the biochemistry and genetics of major pathways responsible for the repair of UV/IR-accrued DNA damage. The outcome of the discussion may be helpful in devising future research in the current context.

  18. Recent advances in the study of ionizing radiation damage and repair.

    Science.gov (United States)

    Arrand, J E; Michael, B D

    1992-06-01

    This workshop, organized under the auspices of the EC Concerted Action Programme on DNA Repair and Cancer, was held at the CRC Gray Laboratory, Northwood, Middlesex, UK, 23-25 October 1991. The 42 participants were drawn mainly from laboratories participating in the EC Concerted Action, with a few visitors from elsewhere. The discussions centred on the increasing convergence of classical radiobiology and biophysics with molecular biology and mammalian cell genetics to study mechanisms of DNA strand break accumulation and repair following exposure to ionizing radiation. There was a strong emphasis on the application of this research both to cancer radiotherapy and to detection of individuals at risk from cancer due to exposure to ionizing radiation. The first two days were organized as six workshop sessions; on the third day we joined forces with Julie Denekamp and dedicated a session to the memory of our late friend and colleague, Nic McNally. The rest of this day was devoted to reviews by his colleagues and collaborators of the fields of research to which he contributed so much. An evening of music and readings, organized by Joanna and Rachel McNally, completed the memorial. Here we review the first seven sessions of the workshop, emphasizing the more recent approaches and the new information they have given us.

  19. Repairable-conditionally repairable damage model based on dual Poisson processes.

    Science.gov (United States)

    Lind, B K; Persson, L M; Edgren, M R; Hedlöf, I; Brahme, A

    2003-09-01

    The advent of intensity-modulated radiation therapy makes it increasingly important to model the response accurately when large volumes of normal tissues are irradiated by controlled graded dose distributions aimed at maximizing tumor cure and minimizing normal tissue toxicity. The cell survival model proposed here is very useful and flexible for accurate description of the response of healthy tissues as well as tumors in classical and truly radiobiologically optimized radiation therapy. The repairable-conditionally repairable (RCR) model distinguishes between two different types of damage, namely the potentially repairable, which may also be lethal, i.e. if unrepaired or misrepaired, and the conditionally repairable, which may be repaired or may lead to apoptosis if it has not been repaired correctly. When potentially repairable damage is being repaired, for example by nonhomologous end joining, conditionally repairable damage may require in addition a high-fidelity correction by homologous repair. The induction of both types of damage is assumed to be described by Poisson statistics. The resultant cell survival expression has the unique ability to fit most experimental data well at low doses (the initial hypersensitive range), intermediate doses (on the shoulder of the survival curve), and high doses (on the quasi-exponential region of the survival curve). The complete Poisson expression can be approximated well by a simple bi-exponential cell survival expression, S(D) = e(-aD) + bDe(-cD), where the first term describes the survival of undamaged cells and the last term represents survival after complete repair of sublethal damage. The bi-exponential expression makes it easy to derive D(0), D(q), n and alpha, beta values to facilitate comparison with classical cell survival models.

  20. The REPAIR Project: Examining the Biological Impacts of Sub-Background Radiation Exposure within SNOLAB, a Deep Underground Laboratory.

    Science.gov (United States)

    Thome, Christopher; Tharmalingam, Sujeenthar; Pirkkanen, Jake; Zarnke, Andrew; Laframboise, Taylor; Boreham, Douglas R

    2017-07-19

    Considerable attention has been given to understanding the biological effects of low-dose ionizing radiation exposure at levels slightly above background. However, relatively few studies have been performed to examine the inverse, where natural background radiation is removed. The limited available data suggest that organisms exposed to sub-background radiation environments undergo reduced growth and an impaired capacity to repair genetic damage. Shielding from background radiation is inherently difficult due to high-energy cosmic radiation. SNOLAB, located in Sudbury, Ontario, Canada, is a unique facility for examining the effects of sub-background radiation exposure. Originally constructed for astroparticle physics research, the laboratory is located within an active nickel mine at a depth of over 2,000 m. The rock overburden provides shielding equivalent to 6,000 m of water, thereby almost completely eliminating cosmic radiation. Additional features of the facility help to reduce radiological contamination from the surrounding rock. We are currently establishing a biological research program within SNOLAB: Researching the Effects of the Presence and Absence of Ionizing Radiation (REPAIR project). We hypothesize that natural background radiation is essential for life and maintains genomic stability, and that prolonged exposure to sub-background radiation environments will be detrimental to biological systems. Using a combination of whole organism and cell culture model systems, the effects of exposure to a sub-background environment will be examined on growth and development, as well as markers of genomic damage, DNA repair capacity and oxidative stress. The results of this research will provide further insight into the biological effects of low-dose radiation exposure as well as elucidate some of the processes that may drive evolution and selection in living systems. This Radiation Research focus issue contains reviews and original articles, which relate to the

  1. Recombinational repair of radiation-induced double-strand breaks occurs in the absence of extensive resection

    Science.gov (United States)

    Westmoreland, James W.; Resnick, Michael A.

    2016-01-01

    Recombinational repair provides accurate chromosomal restitution after double-strand break (DSB) induction. While all DSB recombination repair models include 5′-3′ resection, there are no studies that directly assess the resection needed for repair between sister chromatids in G-2 arrested cells of random, radiation-induced ‘dirty’ DSBs. Using our Pulse Field Gel Electrophoresis-shift approach, we determined resection at IR-DSBs in WT and mutants lacking exonuclease1 or Sgs1 helicase. Lack of either reduced resection length by half, without decreased DSB repair or survival. In the exo1Δ sgs1Δ double mutant, resection was barely detectable, yet it only took an additional hour to achieve a level of repair comparable to WT and there was only a 2-fold dose-modifying effect on survival. Results with a Dnl4 deletion strain showed that remaining repair was not due to endjoining. Thus, similar to what has been shown for a single, clean HO-induced DSB, a severe reduction in resection tract length has only a modest effect on repair of multiple, dirty DSBs in G2-arrested cells. Significantly, this study provides the first opportunity to directly relate resection length at DSBs to the capability for global recombination repair between sister chromatids. PMID:26503252

  2. Tousled kinase activator, gallic acid, promotes homologous recombinational repair and suppresses radiation cytotoxicity in salivary gland cells.

    Science.gov (United States)

    Timiri Shanmugam, Prakash Srinivasan; Nair, Renjith Parameshwaran; De Benedetti, Arrigo; Caldito, Gloria; Abreo, Fleurette; Sunavala-Dossabhoy, Gulshan

    2016-04-01

    Accidental or medical radiation exposure of the salivary glands can gravely impact oral health. Previous studies have shown the importance of Tousled-like kinase 1 (TLK1) and its alternate start variant TLK1B in cell survival against genotoxic stresses. Through a high-throughput library screening of natural compounds, the phenolic phytochemical, gallic acid (GA), was identified as a modulator of TLK1/1B. This small molecule possesses anti-oxidant and free radical scavenging properties, but in this study, we report that in vitro it promotes survival of human salivary acinar cells, NS-SV-AC, through repair of ionizing radiation damage. Irradiated cells treated with GA show improved clonogenic survival compared to untreated controls. And, analyses of DNA repair kinetics by alkaline single-cell gel electrophoresis and γ-H2AX foci immunofluorescence indicate rapid resolution of DNA breaks in drug-treated cells. Study of DR-GFP transgene repair indicates GA facilitates homologous recombinational repair to establish a functional GFP gene. In contrast, inactivation of TLK1 or its shRNA knockdown suppressed resolution of radiation-induced DNA tails in NS-SV-AC, and homology directed repair in DR-GFP cells. Consistent with our results in culture, animals treated with GA after exposure to fractionated radiation showed better preservation of salivary function compared to saline-treated animals. Our results suggest that GA-mediated transient modulation of TLK1 activity promotes DNA repair and suppresses radiation cytoxicity in salivary gland cells.

  3. Genome instability in mismatch repair and its role on radiation-induced cancer

    Energy Technology Data Exchange (ETDEWEB)

    Munakata, Nobuo; Morohoshi, Fumiko [National Cancer Center, Tokyo (Japan). Research Inst

    2000-02-01

    Studies on mismatch repair mechanism have been progressed using Caenorhabditis elegans, a nematode since its genetic analysis is comparatively easy. In this study, homologue gene for mismatch repairing of nematoda were investigated and 3 kinds of homologue genes of mut S; msh G, msh Z and msh F and two kinds of mut L homologue genes were identified. Based on these genes, each cDNA was isolated aiming to determine the sequence and clarify the phylogenetic relationship. Either of msh G, msh Z and msh F is present in the cDNA library, suggesting that these genes might be expressed in every stage of development. Northern analysis was made using the RNA fractions extracted from nematoda at various stages of development as a probe for cDNA of msh G and msh Z, and each corresponding bands were detected for the imago and the matured larva, but not so distinct for the larva and embryo, suggesting that both genes would be regulated in the transcription step at each development stage. Then, resistant larva in which Tcl transposon is activated was cultured and its DNA was extracted to use as a template DNA. Thus, Tcl transposon inserted strains for three of 8 repair related genes were obtained. The passages of these strains were kept comparatively stable. However, the sensitivities to ionizing radiation, ultraviolet light and alkyl agents of these inserted strains were not so different from the control. PCR reaction revealed that DNA fragments of which Tcl was excluded were produced in a certain stage of development. This suggest in vivo exclusion of Tcl in somatic cells. (M.N.)

  4. Repair of the radiation induced rectovaginal fistulas without or with interposition of the bulbocavernosus muscle (Martius procedure)

    Energy Technology Data Exchange (ETDEWEB)

    Aartsen, E.J.; Sindram, I.S.

    1988-04-01

    Two local repair procedures, one without (9) and the other with (14) a bulbocavernosus muscle graft were performed on 20 patients with a radiation induced rectovaginal fistula. Four patients had two procedures successively. The initial success rate of both procedures was 7/9 and 14/14 respectively. Though the initial result of the bulbocavernosus graft was obviously better, in many of the local repair procedures, subclinical radiation damage progressed, resulting in recurrence of rectovaginal fistula (5), rectovesical fistula (4), pararectal abscess (2) etc. After a mean follow up of around 10 years, the success rate of fistula repair decreased to 5/9 and 13/14 and only 2/9 and 6/14 finally remained without a colostomy. A local repair operation should be restricted to carefully selected cases. The musculus gracilis is proposed as a better vascular graft. If the general condition of the patient does not allow more aggressive reconstructive procedures, fistula repair is better cancelled because there is a high risk of subsequent radiation damage.

  5. DNA repair efficiency in germ cells and early mouse embryos and consequences for radiation-induced transgenerational genomic damage

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, Francesco; Wyrobek, Andrew J.

    2009-01-18

    Exposure to ionizing radiation and other environmental agents can affect the genomic integrity of germ cells and induce adverse health effects in the progeny. Efficient DNA repair during gametogenesis and the early embryonic cycles after fertilization is critical for preventing transmission of DNA damage to the progeny and relies on maternal factors stored in the egg before fertilization. The ability of the maternal repair machinery to repair DNA damage in both parental genomes in the fertilizing egg is especially crucial for the fertilizing male genome that has not experienced a DNA repair-competent cellular environment for several weeks prior to fertilization. During the DNA repair-deficient period of spermatogenesis, DNA lesions may accumulate in sperm and be carried into the egg where, if not properly repaired, could result in the formation of heritable chromosomal aberrations or mutations and associated birth defects. Studies with female mice deficient in specific DNA repair genes have shown that: (i) cell cycle checkpoints are activated in the fertilized egg by DNA damage carried by the sperm; and (ii) the maternal genotype plays a major role in determining the efficiency of repairing genomic lesions in the fertilizing sperm and directly affect the risk for abnormal reproductive outcomes. There is also growing evidence that implicates DNA damage carried by the fertilizing gamete as a mediator of postfertilization processes that contribute to genomic instability in subsequent generations. Transgenerational genomic instability most likely involves epigenetic mechanisms or error-prone DNA repair processes in the early embryo. Maternal and embryonic DNA repair processes during the early phases of mammalian embryonic development can have far reaching consequences for the genomic integrity and health of subsequent generations.

  6. Deoxycytidine kinase augments ATM-Mediated DNA repair and contributes to radiation resistance.

    Directory of Open Access Journals (Sweden)

    Yuri L Bunimovich

    Full Text Available Efficient and adequate generation of deoxyribonucleotides is critical to successful DNA repair. We show that ataxia telangiectasia mutated (ATM integrates the DNA damage response with DNA metabolism by regulating the salvage of deoxyribonucleosides. Specifically, ATM phosphorylates and activates deoxycytidine kinase (dCK at serine 74 in response to ionizing radiation (IR. Activation of dCK shifts its substrate specificity toward deoxycytidine, increases intracellular dCTP pools post IR, and enhances the rate of DNA repair. Mutation of a single serine 74 residue has profound effects on murine T and B lymphocyte development, suggesting that post-translational regulation of dCK may be important in maintaining genomic stability during hematopoiesis. Using [(18F]-FAC, a dCK-specific positron emission tomography (PET probe, we visualized and quantified dCK activation in tumor xenografts after IR, indicating that dCK activation could serve as a biomarker for ATM function and DNA damage response in vivo. In addition, dCK-deficient leukemia cell lines and murine embryonic fibroblasts exhibited increased sensitivity to IR, indicating that pharmacologic inhibition of dCK may be an effective radiosensitization strategy.

  7. Transcriptional and Posttranslational Regulation of Nucleotide Excision Repair: The Guardian of the Genome against Ultraviolet Radiation

    Directory of Open Access Journals (Sweden)

    Jeong-Min Park

    2016-11-01

    Full Text Available Ultraviolet (UV radiation from sunlight represents a constant threat to genome stability by generating modified DNA bases such as cyclobutane pyrimidine dimers (CPD and pyrimidine-pyrimidone (6-4 photoproducts (6-4PP. If unrepaired, these lesions can have deleterious effects, including skin cancer. Mammalian cells are able to neutralize UV-induced photolesions through nucleotide excision repair (NER. The NER pathway has multiple components including seven xeroderma pigmentosum (XP proteins (XPA to XPG and numerous auxiliary factors, including ataxia telangiectasia and Rad3-related (ATR protein kinase and RCC1 like domain (RLD and homologous to the E6-AP carboxyl terminus (HECT domain containing E3 ubiquitin protein ligase 2 (HERC2. In this review we highlight recent data on the transcriptional and posttranslational regulation of NER activity.

  8. Cell cycle phase dependent role of DNA polymerase beta in DNA repair and survival after ionizing radiation.

    NARCIS (Netherlands)

    Vermeulen, C.; Verwijs-Janssen, M.; Begg, A.C.; Vens, C.

    2008-01-01

    PURPOSE: The purpose of the present study was to determine the role of DNA polymerase beta in repair and response after ionizing radiation in different phases of the cell cycle. METHODS AND MATERIALS: Synchronized cells deficient and proficient in DNA polymerase beta were irradiated in different pha

  9. Detection and repair of ionizing radiation induced DNA double strand breaks: new developments in non-homologous end joining

    OpenAIRE

    Wang, Chen; Lees-Miller, Susan P.

    2013-01-01

    DNA double-strand breaks (DSBs) are considered the most cytotoxic form of DNA damage. In human cells, the major pathway for the repair of ionizing radiation (IR)-induced DSBs is non-homologous end joining (NHEJ). Here we discuss recent developments in our understanding of the mechanism of NHEJ, the proteins involved and its regulation.

  10. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin.

    Science.gov (United States)

    Surjana, Devita; Halliday, Gary M; Damian, Diona L

    2013-05-01

    Nicotinamide (vitamin B3) protects from ultraviolet (UV) radiation-induced carcinogenesis in mice and from UV-induced immunosuppression in mice and humans. Recent double-blinded randomized controlled Phase 2 studies in heavily sun-damaged individuals have shown that oral nicotinamide significantly reduces premalignant actinic keratoses, and may reduce new non-melanoma skin cancers. Nicotinamide is a precursor of nicotinamide adenine dinucleotide (NAD(+)), an essential coenzyme in adenosine triphosphate (ATP) production. Previously, we showed that nicotinamide prevents UV-induced ATP decline in HaCaT keratinocytes. Energy-dependent DNA repair is a key determinant of cellular survival after exposure to DNA-damaging agents such as UV radiation. Hence, in this study we investigated whether nicotinamide protection from cellular energy loss influences DNA repair. We treated HaCaT keratinocytes with nicotinamide and exposed them to low-dose solar-simulated UV (ssUV). Excision repair was quantified using an assay of unscheduled DNA synthesis. Nicotinamide increased both the proportion of cells undergoing excision repair and the repair rate in each cell. We then investigated ssUV-induced cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxoG) formation and repair by comet assay in keratinocytes and with immunohistochemistry in human skin. Nicotinamide reduced CPDs and 8oxoG in both models and the reduction appeared to be due to enhancement of DNA repair. These results show that nicotinamide enhances two different pathways for repair of UV-induced photolesions, supporting nicotinamide's potential as an inexpensive, convenient and non-toxic agent for skin cancer chemoprevention.

  11. The impact of radiological equipment on patient radiation exposure during endovascular aortic aneurysm repair

    Energy Technology Data Exchange (ETDEWEB)

    Fossaceca, Rita; Guzzardi, Giuseppe; Cerini, Paolo; Carriero, Alessandro [University Hospital ' ' Maggiore della Carita' ' , Radiology Department, Novara (Italy); Brambilla, Marco; Valzano, Serena [University Hospital ' ' Maggiore della Carita' ' , Medical Physics Department, Novara (Italy); Renghi, Alessandra; Brustia, Piero [University Hospital ' ' Maggiore della Carita' ' , Vascular Surgery Department, Novara (Italy)

    2012-11-15

    To compare the patient radiation dose during endovascular aortic aneurysm repair (EVAR) using different types of radiological systems: a mobile fluoroscopic C-arm, mobile angiographic and fixed angiographic equipment. Dose-area products (DAP) were obtained from a retrospective study of 147 consecutive patients, subjected to 153 EVAR procedures during a 3.5-year period. On the basis of these data, entrance surface dose (ESD) and effective dose (ED) were calculated. EVARs were performed using a fluoroscopic C-arm, mobile or fixed angiographic equipment in 79, 26 and 48 procedures, respectively. Fluoroscopy times were essentially equivalent for all the systems, ranging from 15 to 19 min. The clinical outcomes were not significantly different among the systems. Statistically significant differences among radiological equipment grouping were found for DAP (mobile C-arm: 32 {+-} 20 Gy cm{sup 2}; mobile angiography: 362 {+-} 164 Gy cm{sup 2}; fixed angiography: 464 {+-} 274 Gy cm{sup 2}; P < 10{sup -6}), for ESD (mobile C-arm: 0.18 {+-} 0.11 Gy; mobile angiography: 2.0 {+-} 0.8 Gy; fixed angiography: 2.5 {+-} 1.5 Gy; P < 10{sup -6}) and ED (mobile C-arm: 6.2 {+-} 4.5 mSv; mobile angiography: 64 {+-} 26 mSv; fixed angiography: 129 {+-} 76 mSv; P < 10{sup -6}). Radiation dose in EVAR is substantially less with a modern portable C-arm than with a fixed or mobile dedicated angiographic system. (orig.)

  12. Activation of homologous recombination DNA repair in human skin fibroblasts continuously exposed to X-ray radiation.

    Science.gov (United States)

    Osipov, Andreyan N; Grekhova, Anna; Pustovalova, Margarita; Ozerov, Ivan V; Eremin, Petr; Vorobyeva, Natalia; Lazareva, Natalia; Pulin, Andrey; Zhavoronkov, Alex; Roumiantsev, Sergey; Klokov, Dmitry; Eremin, Ilya

    2015-09-29

    Molecular and cellular responses to protracted ionizing radiation exposures are poorly understood. Using immunofluorescence microscopy, we studied the kinetics of DNA repair foci formation in normal human fibroblasts exposed to X-rays at a dose rate of 4.5 mGy/min for up to 6 h. We showed that both the number of γH2AX foci and their integral fluorescence intensity grew linearly with time of irradiation up to 2 h. A plateau was observed between 2 and 6 h of exposure, indicating a state of balance between formation and repair of DNA double-strand breaks. In contrast, the number and intensity of foci formed by homologous recombination protein RAD51 demonstrated a continuous increase during 6 h of irradiation. We further showed that the enhancement of the homologous recombination repair was not due to redistribution of cell cycle phases. Our results indicate that continuous irradiation of normal human cells triggers DNA repair responses that are different from those elicited after acute irradiation. The observed activation of the error-free homologous recombination DNA double-strand break repair pathway suggests compensatory adaptive mechanisms that may help alleviate long-term biological consequences and could potentially be utilized both in radiation protection and medical practices.

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

    Directory of Open Access Journals (Sweden)

    Daiki D Horikawa

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  15. Genome instability of mis-match repair and its role in carcinogenesis due to radiation

    Energy Technology Data Exchange (ETDEWEB)

    Munakata, Nobuo; Morohoshi, Fumiko [National Cancer Center, Tokyo (Japan). Research Inst

    1999-02-01

    Homologue genes, mutS and mutL have been known as a key gene for mismatch repair in E. coli. In this study, identification of such homologue genes in the nematode was attempted using caenorhabditis elegans and three kinds of mutS homologues (mshG, mshZ and mshF) and 2 kinds of mutL ones were identified. From after isolation of these genes, base sequences were analyzed. Then, an insertion mutant in which Tcl transposon is inserted in Exon 13 positioned at the center of mshF was screened and its homozygote where breakage of transposon in somatic cells occurred frequently was obtained and its morphological changes were not significant. In the nematoda, we detected a highly conserved domain in mutS family gene, which is commonly present in yeast and human genes. Based on the amino acid sequence of this domain, four kinds of primers were constructed for PCR reaction using the whole DNA from the nematoda as a template and four DNA fragments of which sizes were almost corresponding to the homologue proteins were produced. From screening of Tc1 insertion mutant for 8 mismatch repair genes, three strains; mshF, rqhW and RqhY were obtained and the gene structures and the positions of Tc1 insertion in these strains were determined. The sensitivities to ionizing radiation, UV and alkyl reagent of these strains were not significantly different from those of the wild strain. (M.N.)

  16. PTH1–34 Blocks Radiation-induced Osteoblast Apoptosis by Enhancing DNA Repair through Canonical Wnt Pathway*

    Science.gov (United States)

    Chandra, Abhishek; Lin, Tiao; Zhu, Ji; Tong, Wei; Huo, Yanying; Jia, Haoruo; Zhang, Yejia; Liu, X. Sherry; Cengel, Keith; Xia, Bing; Qin, Ling

    2015-01-01

    Focal radiotherapy for cancer patients has detrimental effects on bones within the radiation field and the primary clinical signs of bone damage include the loss of functional osteoblasts. We reported previously that daily injection of parathyroid hormone (PTH, 1–34) alleviates radiation-induced osteopenia in a preclinical radiotherapy model by improving osteoblast survival. To elucidate the molecular mechanisms, we irradiated osteoblastic UMR 106-01 cells and calvarial organ culture and demonstrated an anti-apoptosis effect of PTH1–34 on these cultures. Inhibitor assay indicated that PTH exerts its radioprotective action mainly through protein kinase A/β-catenin pathway. γ-H2AX foci staining and comet assay revealed that PTH efficiently promotes the repair of DNA double strand breaks (DSBs) in irradiated osteoblasts via activating the β-catenin pathway. Interestingly, Wnt3a alone also blocked cell death and accelerated DNA repair in primary osteoprogenitors, osteoblastic and osteocytic cells after radiation through the canonical signaling. Further investigations revealed that both Wnt3a and PTH increase the amount of Ku70, a core protein for initiating the assembly of DSB repair machinery, in osteoblasts after radiation. Moreover, down-regulation of Ku70 by siRNA abrogated the prosurvival effect of PTH and Wnt3a on irradiated osteoblasts. In summary, our results identify a novel role of PTH and canonical Wnt signaling in regulating DSB repair machinery and apoptosis in osteoblasts and shed light on using PTH1–34 or Wnt agonist as possible therapy for radiation-induced osteoporosis. PMID:25336648

  17. DSB repair model for mammalian cells in early S and G1 phases of the cell cycle: application to damage induced by ionizing radiation of different quality.

    Science.gov (United States)

    Taleei, Reza; Girard, Peter M; Nikjoo, Hooshang

    2015-02-01

    The purpose of this work is to test the hypothesis that kinetics of double strand breaks (DSB) repair is governed by complexity of DSB. To test the hypothesis we used our recent published mechanistic mathematical model of DSB repair for DSB induced by selected protons, deuterons, and helium ions of different energies representing radiations of different qualities. In light of recent advances in experimental and computational techniques, the most appropriate method to study cellular responses in radiation therapy, and exposures to low doses of ionizing radiations is using mechanistic approaches. To this end, we proposed a 'bottom-up' approach to study cellular response that starts with the DNA damage. Monte Carlo track structure method was employed to simulate initial damage induced in the genomic DNA by direct and indirect effects. Among the different types of DNA damage, DSB are known to be induced in simple and complex forms. The DSB repair model in G1 and early S phases of the cell cycle was employed to calculate the repair kinetics. The model considers the repair of simple and complex DSB, and the DSB produced in the heterochromatin. The inverse sampling method was used to calculate the repair kinetics for each individual DSB. The overall repair kinetics for 500 DSB induced by single tracks of the radiation under test were compared with experimental results. The results show that the model is capable of predicting the repair kinetics for the DSB induced by radiations of different qualities within an accepted range of uncertainty.

  18. Escherichia coli radD (yejH) gene: a novel function involved in radiation resistance and double-strand break repair

    OpenAIRE

    Chen, Stefanie H.; Byrne, Rose T.; Wood, Elizabeth A; Cox, Michael M.

    2015-01-01

    A transposon insertion screen implicated the yejH gene in the repair of ionizing radiation-induced damage. The yejH gene, which exhibits significant homology to the human transcription-coupled DNA repair gene XPB, is involved in the repair of double strand DNA breaks. Deletion of yejH significantly sensitized cells to agents that cause double strand breaks (ionizing radiation, UV radiation, ciprofloxacin). In addition, deletion of both yejH and radA hypersensitized the cells to ionizing radia...

  19. DNA Repair Domain Modeling Can Predict Cell Death and Mutation Frequency for Wide Range Spectrum of Radiation

    Science.gov (United States)

    Viger, Louise; Ponomarev, Artem L.; Plante, Ianik; Evain, Trevor; Penninckx, Sebastien; Blattnig, Steve R.; Costes, Sylvain V.

    2017-01-01

    Exploration missions to Mars and other destinations raise many questions about the health of astronauts. The continuous exposure of astronauts to galactic cosmic rays is one of the main concerns for long-term missions. Cosmic ionizing radiations are composed of different ions of various charges and energies notably, highly charged energy (HZE) particles. The HZE particles have been shown to be more carcinogenic than low-LET radiation, suggesting the severity of chromosomal aberrations induced by HZE particles is one possible explanation. However, most mathematical models predicting cell death and mutation frequency are based on directly fitting various HZE dose response and are in essence empirical approaches. In this work, we assume a simple biological mechanism to model DNA repair and use it to simultaneously explain the low- and high-LET response using the exact same fitting parameters. Our work shows that the geometrical position of DNA repair along tracks of heavy ions are sufficient to explain why high-LET particles can induce more death and mutations. Our model is based on assuming DNA double strand breaks (DSBs) are repaired within repair domain, and that any DSBs located within the same repair domain cluster into one repair unit, facilitating chromosomal rearrangements and increasing the probability of cell death. We introduced this model in 2014 using simplified microdosimetry profiles to predict cell death. In this work, we collaborated with NASA Johnson Space Center to generate more accurate microdosimetry profiles derived by Monte Carlo techniques, taking into account track structure of HZE particles and simulating DSBs in realistic cell geometry. We simulated 224 data points (D, A, Z, E) with the BDSTRACKS model, leading to a large coverage of LET from 10 to 2,400 keV/µm. This model was used to generate theoretical RBE for various particles and energies for both cell death and mutation frequencies. The RBE LET dependence is in agreement with

  20. Participation of DNA-PKcs in DSB repair after exposure to high- and low-LET radiation.

    Science.gov (United States)

    Anderson, Jennifer A; Harper, Jane V; Cucinotta, Francis A; O'Neill, Peter

    2010-08-01

    Cellular lesions (e.g. DSBs) are induced into DNA upon exposure to radiation, with DSB complexity increasing with radiation ionization density. Using M059K and M059J human glioblastoma cells (proficient and deficient in DNA-PKcs activity, respectively), we investigated the repair of DNA damage, including DSBs, induced by high- and low-LET radiation [gamma rays, alpha particles and high-charge and energy (HZE) ions]. In the absence of DNA-PKcs activity, less DSB repair and increased recruitment of RAD51 was seen at 24 h. After exposure to (56)Fe heavy ions, the number of cells with RAD51 tracks was less than the number of cells with gamma-H2AX at 24 h with both cell lines. Using alpha particles, comparable numbers of cells with visible gamma-H2AX and RAD51 were seen at 24 h in both cell lines. M059J cells irradiated with alpha particles accumulated in S phase, with a greater number of cyclin A and RAD51 co-stained cells seen at 24 h compared with M059K cells, where an S-phase block is absent. It is proposed that DNA-PKcs plays a role in the repair of some frank DSBs, which are longer-lived in NHEJ-deficient cells, and some non-DSB clustered damage sites that are converted into DSBs at replication as the cell cycles through to S phase.

  1. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in primary melanocytes.

    Science.gov (United States)

    Thompson, Benjamin C; Surjana, Devita; Halliday, Gary M; Damian, Diona L

    2014-07-01

    Cutaneous melanoma is a significant cause of morbidity and mortality. Nicotinamide is a safe, widely available vitamin that reduces the immune suppressive effects of UV, enhances DNA repair in keratinocytes and has shown promise in the chemoprevention of non-melanoma skin cancer. Here, we report the effect of nicotinamide on DNA damage and repair in primary human melanocytes. Nicotinamide significantly enhanced the repair of oxidative DNA damage (8-oxo-7,8-dihydro-2'-deoxyguanosine) and cyclobutane pyrimidine dimers induced by UV exposure. It also enhanced the repair of 8-oxo-7,8-dihydro-2'-deoxyguanosine induced by the culture conditions in unirradiated melanocytes. A significant increase in the percentage of melanocytes undergoing unscheduled but not scheduled DNA synthesis was observed, confirming that nicotinamide enhances DNA repair in human melanocytes. In summary, nicotinamide, by enhancing DNA repair in melanocytes, is a potential agent for the chemoprevention of cutaneous melanoma.

  2. Enhanced DNA repair of cyclobutane pyrimidine dimers changes the biological response to UV-B radiation

    Energy Technology Data Exchange (ETDEWEB)

    Yarosh, Daniel B

    2002-11-30

    The goal of DNA repair enzyme therapy is the same as that for gene therapy: to rescue a defective proteome/genome by introducing a substitute protein/DNA. The danger of inadequate DNA repair is highlighted in the genetic disease xeroderma pigmentosum. These patients are hypersensitive to sunlight and develop multiple cutaneous neoplasms very early in life. The bacterial DNA repair enzyme T4 endonuclease V was shown over 25 years ago to be capable of reversing the defective repair in xeroderma pigmentosum cells. This enzyme, packaged in an engineered delivery vehicle, has been shown to traverse the stratum corneum, reach the nuclei of living cells of the skin, and enhance the repair of UV-induced cyclobutane pyrimidine dimers (CPD). In such a system, changes in DNA repair, mutagenesis, and cell signaling can be studied without manipulation of the genome.

  3. Regulation of ATM in DNA double strand break repair accounts for the radiosensitivity in human cells exposed to high linear energy transfer ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Xue Lian, E-mail: xuelian@suda.edu.cn [School of Radiation Medicine and Public Health, Medical College of Soochow University, No. 199, Ren' ai Road, Suzhou 215123 (China); Yu Dong, E-mail: ydong@ncc.go.jp [Tumor Endocrinology Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Furusawa, Yoshiya; Okayasu, Ryuichi [Heavy-Ion Radiobiology Research Group, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-shi 263-8555 (Japan); Tong Jian; Cao Jianping; Fan Saijun [School of Radiation Medicine and Public Health, Medical College of Soochow University, No. 199, Ren' ai Road, Suzhou 215123 (China)

    2009-11-02

    High linear energy transfer (LET) radiation shows different biological effects from low-LET radiation. The complex nature of high LET radiation-induced damage, especially the clustered DNA damage, brings about slow repair of DNA double strand breaks (DSBs), which finally lead to higher lethality and chromosome aberration. Ionizing radiation (IR) induced DNA DSBs are repaired by both non-homologous end-joining (NHEJ) and homologous recombination repair (HRR) pathways in mammalian cells. The novel function of ataxia telangiectasia-mutated (ATM) protein is its involvement in the DSB repair of slow kinetics for 'dirty' breaks rejoining by NHEJ, this suggests that ATM may play a more important role in high LET radiation-induced DNA damage. We show here that KU55933, an ATM inhibitor could distinctly lower the clonogenic survival in normal human skin fibroblast cells exposed to carbon ion radiation and dramatically impair the normal process for DSB repair. We also implicated the involvement of ATM in the two pathways of DNA DSB repair, with DNA-PKcs and Rad51 as the representative proteins. The phosphorylation of DNA-PKcs at Thr-2609 with both immunoblotting and immunofluorescent staining indicated an ATM-dependent change, while for Rad51, KU55933 pretreatment could postpone the formation of nuclear Rad51 foci. Interestingly, we also found that pretreatment with chloroquine, an ATM stimulator could protect cells from carbon ion radiation only at lower doses. For doses over 1 Gy, protection was no longer observed. There was a dose-dependent increase for ATM kinase activity, with saturation at about 1 Gy. Chloroquine pretreatment prior to 1 Gy of carbon ion radiation did not enhance the autophosphorylation of ATM at serine 1981. The function of ATM in G2/M checkpoint arrest facilitated DSB repair in high-LET irradiation. Our results provide a possible mechanism for the direct involvement of ATM in DSB repair by high-LET irradiation.

  4. Recognition, signaling, and repair of DNA double-strand breaks produced by ionizing radiation in mammalian cells: the molecular choreography.

    Science.gov (United States)

    Thompson, Larry H

    2012-01-01

    The faithful maintenance of chromosome continuity in human cells during DNA replication and repair is critical for preventing the conversion of normal diploid cells to an oncogenic state. The evolution of higher eukaryotic cells endowed them with a large genetic investment in the molecular machinery that ensures chromosome stability. In mammalian and other vertebrate cells, the elimination of double-strand breaks with minimal nucleotide sequence change involves the spatiotemporal orchestration of a seemingly endless number of proteins ranging in their action from the nucleotide level to nucleosome organization and chromosome architecture. DNA DSBs trigger a myriad of post-translational modifications that alter catalytic activities and the specificity of protein interactions: phosphorylation, acetylation, methylation, ubiquitylation, and SUMOylation, followed by the reversal of these changes as repair is completed. "Superfluous" protein recruitment to damage sites, functional redundancy, and alternative pathways ensure that DSB repair is extremely efficient, both quantitatively and qualitatively. This review strives to integrate the information about the molecular mechanisms of DSB repair that has emerged over the last two decades with a focus on DSBs produced by the prototype agent ionizing radiation (IR). The exponential growth of molecular studies, heavily driven by RNA knockdown technology, now reveals an outline of how many key protein players in genome stability and cancer biology perform their interwoven tasks, e.g. ATM, ATR, DNA-PK, Chk1, Chk2, PARP1/2/3, 53BP1, BRCA1, BRCA2, BLM, RAD51, and the MRE11-RAD50-NBS1 complex. Thus, the nature of the intricate coordination of repair processes with cell cycle progression is becoming apparent. This review also links molecular abnormalities to cellular pathology as much a possible and provides a framework of temporal relationships.

  5. Nimotuzumab enhances radiation sensitivity of NSCLC H292 cells in vitro by blocking epidermal growth factor receptor nuclear translocation and inhibiting radiation-induced DNA damage repair

    Directory of Open Access Journals (Sweden)

    Teng K

    2015-04-01

    Full Text Available Kai Teng,1,2,* Yong Zhang,1,* Xiaoyan Hu,1 Yihui Ding,1 Rui Gong,1 Li Liu1,* 1Department of Thoracic Oncology, Cancer Center of Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Radiation Oncology, Hainan Cancer Hospital, Haikou, Hainan, People’s Republic of China *These authors contributed equally to this work Background: The epidermal growth factor receptor (EGFR signaling pathway plays a significant role in radiation resistance. There is evidence that EGFR nuclear translocation is associated with DNA double-strand breaks (DSB repair. Nimotuzumab has shown the effect of radiosensitization in various cancer cells, but little is known about the relationship between nimotuzumab and EGFR nuclear translocation in non-small cell lung cancer (NSCLC cell lines. In this study, we selected two NSCLC cell lines, namely, H292 (with high EGFR expression and H1975 (with low EGFR expression and explored the mechanisms underlying radiation sensitivity.Methods: MTT assay, clonogenic survival assay, and flow cytometry were performed separately to test cell viability, radiation sensitivity, cell cycle distribution, and apoptosis. Protein γ-H2AX, DNA-PK/p-DNA-PK, and EGFR/p-EGFR expression were further compared both in the cytoplasm and the nucleus with the western blot.Results: Nimotuzumab reduced the viability of H292 cells and sensitized H292 cells to ionizing radiation. The radiation sensitivity enhancement ratio (SER was 1.304 and 1.092 for H292 and H1975 cells, respectively. H292 cells after nimotuzumab administration were arrested at the G0/G1 phase in response to radiation. Apoptosis was without statistical significance in both cell lines. γ-H2AX formation in the combination group (nimotuzumab and radiation increased both in the cytoplasm and the nucleus along with the decreased expression of nuclear EGFR/p-EGFR and p-DNA-PK in H292 cells (P<0.05 that

  6. Use of the comet-FISH assay to compare DNA damage and repair in p53 and hTERT genes following ionizing radiation.

    Directory of Open Access Journals (Sweden)

    Declan J McKenna

    Full Text Available The alkaline single cell gel electrophoresis (comet assay can be combined with fluorescent in situ hybridisation (FISH methodology in order to investigate the localisation of specific gene domains within an individual cell. The number and position of the fluorescent signal(s provides information about the relative damage and subsequent repair that is occurring in the targeted gene domain(s. In this study, we have optimised the comet-FISH assay to detect and compare DNA damage and repair in the p53 and hTERT gene regions of bladder cancer cell-lines RT4 and RT112, normal fibroblasts and Cockayne Syndrome (CS fibroblasts following γ-radiation. Cells were exposed to 5Gy γ-radiation and repair followed for up to 60 minutes. At each repair time-point, the number and location of p53 and hTERT hybridisation spots was recorded in addition to standard comet measurements. In bladder cancer cell-lines and normal fibroblasts, the p53 gene region was found to be rapidly repaired relative to the hTERT gene region and the overall genome, a phenomenon that appeared to be independent of hTERT transcriptional activity. However, in the CS fibroblasts, which are defective in transcription coupled repair (TCR, this rapid repair of the p53 gene region was not observed when compared to both the hTERT gene region and the overall genome, proving the assay can detect variations in DNA repair in the same gene. In conclusion, we propose that the comet-FISH assay is a sensitive and rapid method for detecting differences in DNA damage and repair between different gene regions in individual cells in response to radiation. We suggest this increases its potential for measuring radiosensitivity in cells and may therefore have value in a clinical setting.

  7. DNA Repair Inhibition by Mercuric Chloride in Earthworms after Exposure to Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Tae Ho; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Nili, Mohammad [Dawnesh Radiation Research Institute, Barcelona (Spain); An, Kwang Guk [Chungnam National University, Daejeon (Korea, Republic of)

    2011-10-15

    All organisms are being exposed to harmful factors present in the environment. Ionizing radiation can damage DNA through a series of molecular events depending on the radiation energy. The biological effects due to the combined action of ionizing radiation with the other factor are hard to estimate and predict in advance. Recently International Commission on Radiological Protection (ICRP) requires the effect data of ionizing radiation on non-human biota for the radiological protection of the environment. Earthworms have been identified by the ICRP as one of the reference animals and plants to be used in environmental radiation protection. Particularly, the earthworm Eisenia fetida can be used as a bio-indicator of pollution in soil. This study was performed to investigate the acute genotoxic effects of radiation and the synergistic effects between radiation and mercury in earthworm, E. fetida

  8. Deficiency of the DNA repair protein nibrin increases the basal but not the radiation induced mutation frequency in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wessendorf, Petra [Institute of Medical and Human Genetics, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin (Germany); Vijg, Jan [Albert Einstein College of Medicine, Michael F. Price Center, 1301 Morris Park Avenue, Bronx, NY 10461 (United States); Nussenzweig, André [Laboratory of Genome Integrity, National Cancer Institute, National Institute of Health, 37 Convent Drive, Room 1106, Bethesda, MD 20892 (United States); Digweed, Martin, E-mail: martin.digweed@charite.de [Institute of Medical and Human Genetics, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin (Germany)

    2014-11-15

    Highlights: • lacZ mutant frequencies measured in vivo in mouse models of radiosensitive Nijmegen Breakage Syndrome. • Spontaneous mutation frequencies are increased in lymphatic tissue due to Nbn mutation. • Single base transitions, not deletions, dominate the mutation spectrum. • Radiation induced mutation frequencies are not increased due to Nbn mutation. - Abstract: Nibrin (NBN) is a member of a DNA repair complex together with MRE11 and RAD50. The complex is associated particularly with the repair of DNA double strand breaks and with the regulation of cell cycle check points. Hypomorphic mutation of components of the complex leads to human disorders characterised by radiosensitivity and increased tumour occurrence, particularly of the lymphatic system. We have examined here the relationship between DNA damage, mutation frequency and mutation spectrum in vitro and in vivo in mouse models carrying NBN mutations and a lacZ reporter plasmid. We find that NBN mutation leads to increased spontaneous DNA damage in fibroblasts in vitro and high basal mutation rates in lymphatic tissue of mice in vivo. The characteristic mutation spectrum is dominated by single base transitions rather than the deletions and complex rearrangements expected after abortive repair of DNA double strand breaks. We conclude that in the absence of wild type nibrin, the repair of spontaneous errors, presumably arising during DNA replication, makes a major contribution to the basal mutation rate. This applies also to cells heterozygous for an NBN null mutation. Mutation frequencies after irradiation in vivo were not increased in mice with nibrin mutations as might have been expected considering the radiosensitivity of NBS patient cells in vitro. Evidently apoptosis is efficient, even in the absence of wild type nibrin.

  9. Use of the γ-H2AX assay to investigate DNA repair dynamics following multiple radiation exposures.

    Directory of Open Access Journals (Sweden)

    Luca G Mariotti

    Full Text Available Radiation therapy is one of the most common and effective strategies used to treat cancer. The irradiation is usually performed with a fractionated scheme, where the dose required to kill tumour cells is given in several sessions, spaced by specific time intervals, to allow healthy tissue recovery. In this work, we examined the DNA repair dynamics of cells exposed to radiation delivered in fractions, by assessing the response of histone-2AX (H2AX phosphorylation (γ-H2AX, a marker of DNA double strand breaks. γ-H2AX foci induction and disappearance were monitored following split dose irradiation experiments in which time interval between exposure and dose were varied. Experimental data have been coupled to an analytical theoretical model, in order to quantify key parameters involved in the foci induction process. Induction of γ-H2AX foci was found to be affected by the initial radiation exposure with a smaller number of foci induced by subsequent exposures. This was compared to chromatin relaxation and cell survival. The time needed for full recovery of γ-H2AX foci induction was quantified (12 hours and the 1:1 relationship between radiation induced DNA double strand breaks and foci numbers was critically assessed in the multiple irradiation scenarios.

  10. Neural Network Enhanced Structure Determination of Osteoporosis, Immune System, and Radiation Repair Proteins Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation will utilize self learning neural network technology to determine the structure of osteoporosis, immune system disease, and excess radiation...

  11. BioSentinel: Mission Development of a Radiation Biosensor to Gauge DNA Damage and Repair Beyond Low Earth Orbit on a 6U Nanosatellite

    Science.gov (United States)

    Sanchez, Hugo; Lewis, Brian; Hanel, Robert

    2015-01-01

    We are designing and developing a 6U (10 x 22 x 34 cm; 14 kg) nanosatellite as a secondary payload to fly aboard NASAs Space Launch System (SLS) Exploration Mission (EM) 1, scheduled for launch in late 2017. For the first time in over forty years, direct experimental data from biological studies beyond low Earth orbit (LEO) will be obtained during BioSentinels 12- to 18-month mission. BioSentinel will measure the damage and repair of DNA in a biological organism and allow us to compare that to information from onboard physical radiation sensors. In order to understand the relative contributions of the space environments two dominant biological perturbations, reduced gravity and ionizing radiation, results from deep space will be directly compared to data obtained in LEO (on ISS) and on Earth. These data points will be available for validation of existing biological radiation damage and repair models, and for extrapolation to humans, to assist in mitigating risks during future long-term exploration missions beyond LEO. The BioSentinel Payload occupies 4U of the spacecraft and will utilize the monocellular eukaryotic organism Saccharomyces cerevisiae (yeast) to report DNA double-strand-break (DSB) events that result from ambient space radiation. DSB repair exhibits striking conservation of repair proteins from yeast to humans. Yeast was selected because of 1) its similarity to cells in higher organisms, 2) the well-established history of strains engineered to measure DSB repair, 3) its spaceflight heritage, and 4) the wealth of available ground and flight reference data. The S. cerevisiae flight strain will include engineered genetic defects to prevent growth and division until a radiation-induced DSB activates the yeasts DNA repair mechanisms. The triggered culture growth and metabolic activity directly indicate a DSB and its successful repair. The yeast will be carried in the dry state within the 1-atm PL container in 18 separate fluidics cards with each card

  12. UVA radiation is highly mutagenic in cells that are unable to repair 7,8-dihydro-8-oxoguanine in Saccharomyces cerevisiae.

    Science.gov (United States)

    Kozmin, S; Slezak, G; Reynaud-Angelin, A; Elie, C; de Rycke, Y; Boiteux, S; Sage, E

    2005-09-20

    UVA (320-400 nm) radiation constitutes >90% of the environmentally relevant solar UV radiation, and it has been proposed to have a role in skin cancer and aging. Because of the popularity of UVA tanning beds and prolonged periods of sunbathing, the potential deleterious effect of UVA has emerged as a source of concern for public health. Although generally accepted, the impact of DNA damage on the cytotoxic, mutagenic, and carcinogenic effect of UVA radiation remains unclear. In the present study, we investigated the sensitivity of a panel of yeast mutants affected in the processing of DNA damage to the lethal and mutagenic effect of UVA radiation. The data show that none of the major DNA repair pathways, such as base excision repair, nucleotide excision repair, homologous recombination, and postreplication repair, efficiently protect yeast from the lethal action of UVA radiation. In contrast, the results show that the Ogg1 DNA glycosylase efficiently prevents UVA-induced mutagenesis, suggesting the formation of oxidized guanine residues. Furthermore, sequence analysis of UVA-induced canavanine-resistant mutations reveals a bias in favor of GC-->TA events when compared with spontaneous or H(2)O(2)-, UVC-, and gamma-ray- induced canavanine-resistant mutations in the WT strain. Taken together, our data point out a major role of oxidative DNA damage, mostly 7,8-dihydro-8-oxoguanine, in the genotoxicity of UVA radiation in the yeast Saccharomyces cerevisiae. Therefore, the capacity of skin cells to repair 7,8-dihydro-8-oxoguanine may be a key parameter in the mutagenic and carcinogenic effect of UVA radiation in humans.

  13. Repair of radiation-induced heat-labile sites is independent of DNA-PKcs, XRCC1 or PARP

    Energy Technology Data Exchange (ETDEWEB)

    Stenerl& #246; w, Bo; Karlsson, Karin H.; Radulescu, Irina; Rydberg, Bjorn; Stenerlow, Bo

    2008-04-29

    Ionizing radiation induces a variety of different DNA lesions: in addition to the most critical DNA damage, the DSB, numerous base alterations, SSBs and other modifications of the DNA double-helix are formed. When several non-DSB lesions are clustered within a short distance along DNA, or close to a DSB, they may interfere with the repair of DSBs and affect the measurement of DSB induction and repair. We have previously shown that a substantial fraction of DSBs measured by pulsed-field gel electrophoresis (PFGE) are in fact due to heat-labile sites (HLS) within clustered lesions, thus reflecting an artifact of preparation of genomic DNA at elevated temperature. To further characterize the influence of HLS on DSB induction and repair, four human cell lines (GM5758, GM7166, M059K, U-1810) with apparently normal DSB rejoining were tested for bi-phasic rejoining after gamma irradiation. When heat-released DSBs were excluded from the measurements the fraction of fast rejoining decreased to less than 50% of the total. However, neither the half-times of the fast (t{sub 1/2} = 7-8 min) or slow (t{sub 1/2} = 2.5 h) DSB rejoining were changed significantly. At t=0 the heat-released DSBs accounted for almost 40% of the DSBs, corresponding to 10 extra DSB/cell/Gy in the initial DSB yield. These heat-released DSBs were repaired within 60-90 min in all tested cells, including M059K cells treated with wortmannin or DNA-PKcs defect M059J cells. Furthermore, cells lacking XRCC1 or Poly(ADP-ribose) polymerase-1 (PARP-1) rejoined both total DSBs and heat-released DSBs similar to normal cells. In summary, the presence of heat-labile sites have a substantial impact on DSB induction yields and DSB rejoining rates measured by pulsed-field gel electrophoresis, and HLS repair is independent of DNA-PKcs, XRCC1 and PARP.

  14. Effects of UV-B radiation on tetraspores of Chondrus ocellatus Holm (Rhodophyta), and effects of red and blue light on repair of UV-B-induced damage

    Science.gov (United States)

    Ju, Qing; Xiao, Hui; Wang, You; Tang, Xuexi

    2015-05-01

    We evaluated the effects of red and blue light on the repair of UV-B radiation-induced damage in tetraspores of Chondrus ocellatus Holm. Tetraspores of C. ocellatus were treated with different UV-B radiation levels (0, 36, 72, 108, 144 and 180 J/m2), and thereafter subjected to PAR, darkness, or red or blue light during a 2-h repair stage, each day for 48 days. The diameters and cellular contents of cyclobutane pyrimidine dimmers (CPDs), chlorophyll a (Chl a), phycoerythrin, and UV-B-absorbing mycosporinelike amino acids (MAAs) contents of the tetraspores were determined. Our results show that low doses of UV-B radiation (36 and 72 J/m2) promoted the growth of C. ocellatus; however, increased UV-B radiation gradually reduced the C. ocellatus growth (greater than 72 J/m2). The MAAs (palythine and asterina-330) in C. ocellatus were detected and analyzed by LC/MS. Our results suggest that moderate red light could induce the growth of this alga in aquaculture. In addition, photorepair was inhibited by red light, so there may be some other DNA repair mechanism activated by red light. Blue light promoted the activity of DNA photolyase, greatly improving remediation efficiency. Red and blue lights were found to reduce the capacity of C. ocellatus to form MAAs. Therefore, PAR, red light, and blue light play different roles during the repair processes for damage induced by UV-B radiation.

  15. In vivo effects of UV radiation on multiple endpoints and expression profiles of DNA repair and heat shock protein (Hsp) genes in the cycloid copepod Paracyclopina nana

    Energy Technology Data Exchange (ETDEWEB)

    Won, Eun-Ji; Han, Jeonghoon [Department of Biological Science, College of Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Lee, Yeonjung; Kumar, K. Suresh; Shin, Kyung-Hoon [Department of Marine Sciences and Convergent Technology, College of Science and Technology, Hanyang University, Ansan 426-791 (Korea, Republic of); Lee, Su-Jae [Department of Life Sciences, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Park, Heum Gi, E-mail: hgpark@gwnu.ac.kr [Department of Marine Resource Development, College of Life Sciences, Gangneung-Wonju National University, Gangneung 210-702 (Korea, Republic of); Lee, Jae-Seong, E-mail: jslee2@skku.edu [Department of Biological Science, College of Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)

    2015-08-15

    Highlights: • UV-B radiation induced a significant reduction of the re-brooding rate of ovigerous females. • A dose-dependent decrease in food ingestion and the rate of assimilation to the body upon UV radiation. • Expression of base excision repair-associated and hsp chaperoning genes was significantly increased upon UV radiation in P. nana. - Abstract: To evaluate the effects of ultraviolet (UV) radiation on energy acquisition and consumption, the copepod Paracyclopina nana was irradiated with several doses (0–3 kJ/m{sup 2}) of UV. After UV radiation, we measured the re-brooding success, growth pattern of newly hatched nauplii, ingestion rate, and assimilation of diet. In addition, we checked the modulated patterns of DNA repair and heat shock protein (hsp) chaperoning genes of P. nana. UV-B radiation induced a significant reduction (7–87%) of the re-brooding rate of ovigerous females, indicating that UV-induced egg sac damage is closely correlated with a reduction in the hatching rate of UV-irradiated ovigerous female offspring. Using chlorophyll a and stable carbon isotope incubation experiments, we found a dose-dependent decrease (P < 0.05) in food ingestion and the rate of assimilation to the body in response to UV radiation, implying that P. nana has an underlying ability to shift its balanced-energy status from growth and reproduction to DNA repair and adaptation. Also, expression of P. nana base excision repair (BER)-associated genes and hsp chaperoning genes was significantly increased in response to UV radiation in P. nana. These findings indicate that even 1 kJ/m{sup 2} of UV radiation induces a reduction in reproduction and growth patterns, alters the physiological balance and inhibits the ability to cope with UV-induced damage in P. nana.

  16. Micronuclei in humans induced by exposure to low level of ionizing radiation: influence of polymorphisms in DNA repair genes

    Energy Technology Data Exchange (ETDEWEB)

    Angelini, Sabrina [Department of Pharmacology, University of Bologna, Via Irnerio 48, Bologna 40126 (Italy) and Department of Biosciences, Karolinska Institute, Novum, Huddinge 141 57 (Sweden)]. E-mail: angelini@biocfarm.unibo.it; Kumar, Rajiv [Department of Biosciences, Karolinska Institute, Novum, Huddinge 141 57 (Sweden); Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg (Germany); Carbone, Fabio [Department of Pharmacology, University of Bologna, Via Irnerio 48, Bologna 40126 (Italy); Maffei, Francesca [Department of Pharmacology, University of Bologna, Via Irnerio 48, Bologna 40126 (Italy); Forti, Giorgio Cantelli [Department of Pharmacology, University of Bologna, Via Irnerio 48, Bologna 40126 (Italy); Violante, Francesco Saverio [Department of Biosciences, Karolinska Institute, Novum, Huddinge 141 57 (Sweden); Occupational Medicine Unit, S. Orsola-Malpighi Hospital, Via Pelagi 9, Bologna 40100 (Italy); Lodi, Vittorio [Department of Biosciences, Karolinska Institute, Novum, Huddinge 141 57 (Sweden); Curti, Stefania [Department of Biosciences, Karolinska Institute, Novum, Huddinge 141 57 (Sweden); Hemminki, Kari [Department of Biosciences, Karolinska Institute, Novum, Huddinge 141 57 (Sweden); Hrelia, Patrizia [Department of Pharmacology, University of Bologna, Via Irnerio 48, Bologna 40126 (Italy)

    2005-02-15

    Understanding the risks deriving from protracted exposure to low doses of ionizing radiation has remarkable societal importance in view of the large number of work settings in which sources of IR are encountered. To address this question, we studied the frequency of micronuclei (MN), which is an indicator of DNA damage, in a population exposed to low levels of ionizing radiation and in matched controls. In both exposed population and controls, the possible influence of single nucleotide polymorphisms in XRCC1, XRCC3 and XPD genes on the frequency of micronuclei was also evaluated. We also considered the effects of confounding factors, like smoking status, age and gender. The results indicated that MN frequency was significantly higher in the exposed workers than in the controls [8.62 {+-} 2.80 versus 6.86 {+-} 2.65; P = 0.019]. Radiological workers with variant alleles for XRCC1 or XRCC3 polymorphisms or wild-type alleles for XPD exon 23 or 10 polymorphisms showed a significantly higher MN frequency than controls with the same genotypes. Smoking status did not affect micronuclei frequency either in exposed workers or controls, while age was associated with increased MN frequency in the exposed only. In the combined population, gender but not age exerted an influence on the yield of MN, being higher in females than in males. Even though there is a limitation in this study due to the small number of subjects, these results suggest that even exposures to low level of ionizing radiation could have genotoxic effects and that XRCC3, XRCC1 and XPD polymorphisms might contribute to the increased genetic damage in susceptible individuals occupationally exposed to chronic low levels of ionizing radiation. For a clear conclusion on the induction of DNA damage caused by protracted exposure to low doses of ionizing radiation and the possible influence of genetic polymorphism in DNA repair genes larger studies are needed.

  17. The Regularities of Mutagenic Action of gamma-Radiation on Vegetative Bacillus subtilis Cells with Different Repair Genotype

    CERN Document Server

    Boreyko, A V; Krasavin, E A

    2000-01-01

    The regularities of induction of his^-\\to his^+ mutations in vegetative Bacillus subtilis cells with different repair capacity after gamma-irradiation have been studied. The wild type cells, polA1, recE4, recA, recP, add5, recH were used in experiments. It was shown that radiation-induced mutagenesis is determined by a repair genotype of cells. The blocking of different reparation genes is reflected on mutagenesis ratio by the various ways. A frequency of induction mutations in polA strain is higher than in wild type cells and it is characterized by the linearly-quadratic dose curve. The different rec^- strains that belong to various epistatic groups reveal an unequal mutation induction. The add5 and recP strains are characterized by the high-level induction mutations in contrast with the wild type cells. The mutagenesis in recE and recH strains, on the contrary, sharply reduces. The different influence of rec genes inhering to various epistatic groups on mutagenesis in Bacillus subtilis cells probably reflec...

  18. [Studies of the repair of radiation-induced genetic damage in Drosophila]. Annual progress report, October 1, 1988--June 1, 1989

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1989-12-31

    The primary goal of this study is to achieve a more thorough understanding of the mechanisms employed by higher organisms to repair DNA damage induced by both ionizing and nonionizing radiation. These studies are also contributing to an improved understanding of the processes of mutagenesis and carcinogenesis in higher eukaryotes. The studies employ Drosophila as a model organism for investigating repair functions that are common to all higher eukaryotes. Drosophila was chosen in the early phases of this study primarily because of the ease with which one can isolate and characterize repair-deficient mutants in a metazoan organism. The laboratory has gone on to investigate the metabolic defects of such mutants while others have performed complementary genetic and cytogenetic studies which relate DNA repair processes to mutagenesis and chromosome stability. The repair studies have exploited the capacity to introduce mutant Drosophila cells into tissue culture and thereby compare repair defects directly with those of homologous human disorders. Researchers are currently employing recombinant DNA technology to investigate the mechanisms of the DNA repair pathways defined by those mutants.

  19. Sublethal effects of industrial chemicals on fish fingerlings ( Tilapia ...

    African Journals Online (AJOL)

    Sublethal effects of industrial chemicals on fish fingerlings ( Tilapia guineensis ) ... African Journal of Biotechnology ... sublethal concentrations (1.56, 3.13 mg/l) of neatex (industrial detergent) and norust CR 486 (corrosion inhibitor) using the ...

  20. DOE contractors' workshop: Cellular and molecular aspects of radiation induced DNA damage and repair

    Energy Technology Data Exchange (ETDEWEB)

    1987-01-01

    For four decades the US Department of Energy and its predecessors have been the lead federal agency in supporting radiation biology research. Over the years emphasis in this program has gradually shifted from dose-effect studies on animals to research on the effects of radiations of various qualities on cells and molecules. Mechanistic studies on the action of radiation at the subcellular level are few in number and there is a need for more research in this area if we are to gain a better understanding of how radiation affects living cells. The intent of this workshop was to bring together DOE contractors and grantees who are investigating the effects of radiation at the cellular and molecular levels. The aims were to foster the exchange of information on research projects and experimental results, promote collaborative research efforts, and obtain an overview of research currently supported by the Health Effects Research Division of the Office of Health and Environmental Research. The latter is needed by the Office for program planning purposes. This report on the workshop which took place in Albuquerque, New Mexico on March 10-11, 1987, includes an overview with future research recommendations, extended abstracts of the plenary presentations, shorter abstracts of each poster presentation, a workshop agenda and the names and addresses of the attendees.

  1. Low Dose Radiation-Induced Genome and Epigenome Instability Symposium and Epigenetic Mechanisms, DNA Repair, and Chromatin Symposium at the EMS 2008 Annual Meeting - October 2008

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, William F; Kovalchuk, Olga; Dolinoy, Dana C; Dubrova, Yuri E; Coleman, Matthew A; Schär, Primo; Pogribny, Igor; Hendzel, Michael

    2010-02-19

    The Low Dose Radiation Symposium thoughtfully addressed ionizing radiation non-mutational but transmissable alterations in surviving cells. Deregulation of epigenetic processes has been strongly implicated in carcinogenesis, and there is increasing realization that a significant fraction of non-targeted and adaptive mechanisms in response to ionizing radiation are likely to be epigenetic in nature. Much remains to be learned about how chromatin and epigenetic regulators affect responses to low doses of radiation, and how low dose radiation impacts other epigenetic processes. The Epigenetic Mechanisms Symposium focused on on epigenetic mechanisms and their interplay with DNA repair and chromatin changes. Addressing the fact that the most well understood mediators of epigenetic regulation are histone modifications and DNA methylation. Low levels of radiation can lead to changes in the methylation status of certain gene promoters and the expression of DNA methyltransferases, However, epigenetic regulation can also involve changes in higher order chromosome structure.

  2. In vivo effects of UV radiation on multiple endpoints and expression profiles of DNA repair and heat shock protein (Hsp) genes in the cycloid copepod Paracyclopina nana.

    Science.gov (United States)

    Won, Eun-Ji; Han, Jeonghoon; Lee, Yeonjung; Kumar, K Suresh; Shin, Kyung-Hoon; Lee, Su-Jae; Park, Heum Gi; Lee, Jae-Seong

    2015-08-01

    To evaluate the effects of ultraviolet (UV) radiation on energy acquisition and consumption, the copepod Paracyclopina nana was irradiated with several doses (0-3kJ/m(2)) of UV. After UV radiation, we measured the re-brooding success, growth pattern of newly hatched nauplii, ingestion rate, and assimilation of diet. In addition, we checked the modulated patterns of DNA repair and heat shock protein (hsp) chaperoning genes of P. nana. UV-B radiation induced a significant reduction (7-87%) of the re-brooding rate of ovigerous females, indicating that UV-induced egg sac damage is closely correlated with a reduction in the hatching rate of UV-irradiated ovigerous female offspring. Using chlorophyll a and stable carbon isotope incubation experiments, we found a dose-dependent decrease (Pnana has an underlying ability to shift its balanced-energy status from growth and reproduction to DNA repair and adaptation. Also, expression of P. nana base excision repair (BER)-associated genes and hsp chaperoning genes was significantly increased in response to UV radiation in P. nana. These findings indicate that even 1kJ/m(2) of UV radiation induces a reduction in reproduction and growth patterns, alters the physiological balance and inhibits the ability to cope with UV-induced damage in P. nana.

  3. Potential Repair of Escherichia coli DNA following Exposure to UV Radiation from Both Medium- and Low-Pressure UV Sources Used in Drinking Water Treatment

    Science.gov (United States)

    Zimmer, J. L.; Slawson, R. M.

    2002-01-01

    The increased use of UV radiation as a drinking water treatment technology has instigated studies of the repair potential of microorganisms following treatment. This study challenged the repair potential of an optimally grown nonpathogenic laboratory strain of Escherichia coli after UV radiation from low- and medium-pressure lamps. Samples were irradiated with doses of 5, 8, and 10 mJ/cm2 from a low-pressure lamp and 3, 5, 8, and 10 mJ/cm2 from a medium-pressure UV lamp housed in a bench-scale collimated beam apparatus. Following irradiation, samples were incubated at 37°C under photoreactivating light or in the dark. Sample aliquots were analyzed for up to 4 h following incubation using a standard plate count. Results of this study showed that E. coli underwent photorepair following exposure to the low-pressure UV source, but no repair was detectable following exposure to the medium-pressure UV source at the initial doses examined. Minimal repair was eventually observed upon medium-pressure UV lamp exposure when doses were lowered to 3 mJ/cm2. This study clearly indicates differences in repair potential under laboratory conditions between irradiation from low-pressure and medium-pressure UV sources of the type used in water treatment. PMID:12089006

  4. Damage Avoidance and Repair Mechanisms of Extreme Halophiles to Ionizing Radiation

    Science.gov (United States)

    2013-07-01

    tolerance   to   desiccation  that...abilities.   Early   work   on   the   desiccation   resistance   of   extremely   radiation-­‐resistant   bacteria   revealed...imparts  IR  resistance  to  these  organisms.  The  distribution  of  extremely   IR  and   desiccation

  5. ON THE NECESSITY OF RADIATION SURVEY OF THE BUILDINGS AFTER THE CONSTRUCTION, REPAIR OR RECONSTRUCTION

    Directory of Open Access Journals (Sweden)

    G. A. Gorsky

    2010-01-01

    Full Text Available The article presents regulation of radon concentration in the air of dwellings and public buildings in Russia in the historical aspect. It is shown with a specific reference to Saint-Petersburg that implementation of obligatory radiation survey of new buildings has led to the significant reduction of radon concentration in the dwelling air and, consequently, the levels of population exposure due to natural sources.

  6. BioSentinel: Mission Development of a Radiation Biosensor to Gauge DNA Damage and Repair Beyond Low Earth Orbit on a 6U Nanosatellite.

    Science.gov (United States)

    Lewis, Brian; Hanel, Robert; Bhattacharya, Sharmila; Ricco, Antonion J.; Agasid, Elwood; Reiss-Bubenheim, Debra; Straume, Tore; Parra, Macerena; Boone, Travis; Santa Maria, Sergio; hide

    2015-01-01

    We are designing and developing a "6U" (10 x 22 x 34 cm; 14 kg) nanosatellite as a secondary payload to fly aboard NASA's Space Launch System (SLS) Exploration Mission (EM) 1, scheduled for launch in late 2017. For the first time in over forty years, direct experimental data from biological studies beyond low Earth orbit (LEO) will be obtained during BioSentinel's 12- to 18- month mission. BioSentinel will measure the damage and repair of DNA in a biological organism and allow us to compare that to information from onboard physical radiation sensors. In order to understand the relative contributions of the space environment's two dominant biological perturbations, reduced gravity and ionizing radiation, results from deep space will be directly compared to data obtained in LEO (on ISS) and on Earth. These data points will be available for validation of existing biological radiation damage and repair models, and for extrapolation to humans, to assist in mitigating risks during future long-term exploration missions beyond LEO. The BioSentinel Payload occupies 4U of the spacecraft and will utilize the monocellular eukaryotic organism Saccharomyces cerevisiae (yeast) to report DNA double-strand-break (DSB) events that result from ambient space radiation. DSB repair exhibits striking conservation of repair proteins from yeast to humans. Yeast was selected because of 1) its similarity to cells in higher organisms, 2) the well-established history of strains engineered to measure DSB repair, 3) its spaceflight heritage, and 4) the wealth of available ground and flight reference data. The S. cerevisiae flight strain will include engineered genetic defects to prevent growth and division until a radiation-induced DSB activates the yeast's DNA repair mechanisms. The triggered culture growth and metabolic activity directly indicate a DSB and its successful repair. The yeast will be carried in the dry state within the 1-atm P/L container in 18 separate fluidics cards with each

  7. Effect of chronic low dose natural radiation in human peripheral blood mononuclear cells: Evaluation of DNA damage and repair using the alkaline comet assay

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, P.R. Vivek, E-mail: prvkumar06@gmail.com [Low Level Radiation Research Laboratory, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, IRE Campus, Beach Road, Kollam 691 001, Kerala (India); Seshadri, M. [Low Level Radiation Research Section, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India); Jaikrishan, G. [Low Level Radiation Research Laboratory, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, IRE Campus, Beach Road, Kollam 691 001, Kerala (India); Das, Birajalaxmi [Low Level Radiation Research Section, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)

    2015-05-15

    Highlights: • Effect of chronic low dose natural radiation in radio adaptive response studied. • PBMCs of subjects from NLNRA and HLNRA were challenged with gamma radiation. • DNA damage and repair in PBMCs was compared using the alkaline comet assay. • Significant reduction in DNA damage in subjects of high dose group from HLNRA noted. • Probable induction of an in vivo radio adaptive response in subjects from HLNRA. - Abstract: This study investigates whether peripheral blood mononuclear cells (PBMCs) from inhabitants of Kerala in southwest India, exposed to chronic low dose natural radiation in vivo (>1 mSv year{sup −1}), respond with a radioadaptive response to a challenging dose of gamma radiation. Toward this goal, PBMCs isolated from 77 subjects from high-level natural radiation areas (HLNRA) and 37 subjects from a nearby normal level natural radiation area (NLNRA) were challenged with 2 Gy and 4 Gy gamma radiation. Subjects from HLNRA were classified based on the mean annual effective dose received, into low dose group (LDG) and high dose group (HDG) with mean annual effective doses of 2.69 mSv (N = 43, range 1.07 mSv year{sup −1} to 5.55 mSv year{sup −1}) and 9.62 mSv (N = 34, range 6.07 mSv year{sup −1} to17.41 mSv year{sup −1}), respectively. DNA strand breaks and repair kinetics (at 7 min, 15 min and 30 min after 4 Gy) were evaluated using the alkaline single cell gel electrophoresis (comet) assay. Initial levels of DNA strand breaks observed after either a 2 Gy or a 4 Gy challenging dose were significantly lower in subjects of the HDG from HLNRA compared to subjects of NLNRA (2 Gy, P = 0.01; 4 Gy, P = 0.02) and LDG (2 Gy P = 0.01; 4 Gy, P = 0.05). Subjects of HDG from HLNRA showed enhanced rejoining of DNA strand breaks (HDG/NLNRA, P = 0.06) during the early stage of repair (within 7 min). However at later times a similar rate of rejoining of strand breaks was observed across the groups (HDG, LDG and NLNRA). Preliminary results from

  8. Allograft pretreatment for the repair of sciatic nerve defects:green tea polyphenolsversus radiation

    Institute of Scientific and Technical Information of China (English)

    Sheng-hu Zhou; Ping Zhen; Shen-song Li; Xiao-yan Liang; Ming-xuan Gao; Qi Tian; Xu-sheng Li

    2015-01-01

    Pretreatment of nerve allografts by exposure to irradiation or green tea polyphenols can elimi-nate neuroimmunogenicity, inhibit early immunological rejection, encourage nerve regeneration and functional recovery, improve tissue preservation, and minimize postoperative infection. In the present study, we investigate which intervention achieves better results. We produced a 1.0 cm sciatic nerve defect in rats, and divided the rats into four treatment groups: autograft, fresh nerve allograft, green tea polyphenol-pretreated (1 mg/mL, 4°C) nerve allograft, and irradiation-pre-treated nerve allograft (26.39 Gy/min for 12 hours; total 19 kGy). The animals were observed, and sciatic nerve electrophysiology, histology, and transmission electron microscopy were carried out at 6 and 12 weeks after grafting. The circumference and structure of the transplanted nerve in rats that received autografts or green tea polyphenol-pretreated nerve allografts were similar to those of the host sciatic nerve. Compared with the groups that received fresh or irradiation-pre-treated nerve allografts, motor nerve conduction velocity in the autograft and fresh nerve allograft groups was greater, more neurites grew into the allografts, Schwann cell proliferation was evident, and a large number of new blood vessels was observed; in addition, massive myelinated nerve ifbers formed, and abundant microiflaments and microtubules were present in the axoplasm. Our ifndings indicate that nerve allografts pretreated by green tea polyphenols are equivalent to trans-planting autologous nerves in the repair of sciatic nerve defects, and promote nerve regeneration. Pretreatment using green tea polyphenols is better than pretreatment with irradiation.

  9. UV radiation effects on a DNA repair enzyme: conversion of a [4Fe-4S](2+) cluster into a [2Fe-2S] (2+).

    Science.gov (United States)

    Folgosa, Filipe; Camacho, Inês; Penas, Daniela; Guilherme, Márcia; Fróis, João; Ribeiro, Paulo A; Tavares, Pedro; Pereira, Alice S

    2015-03-01

    Organisms are often exposed to different types of ionizing radiation that, directly or not, will promote damage to DNA molecules and/or other cellular structures. Because of that, organisms developed a wide range of response mechanisms to deal with these threats. Endonuclease III is one of the enzymes responsible to detect and repair oxidized pyrimidine base lesions. However, the effect of radiation on the structure/function of these enzymes is not clear yet. Here, we demonstrate the effect of UV-C radiation on E. coli endonuclease III through several techniques, namely UV-visible, fluorescence and Mössbauer spectroscopies, as well as SDS-PAGE and electrophoretic mobility shift assay. We demonstrate that irradiation with a UV-C source has dramatic consequences on the absorption, fluorescence, structure and functionality of the protein, affecting its [4Fe-4S] cluster and its DNA-binding ability, which results in its inactivation. An UV-C radiation-induced conversion of the [4Fe-4S](2+) into a [2Fe-2S](2+) was observed for the first time and proven by Mössbauer and UV-visible analysis. This work also shows that the DNA-binding capability of endonuclease III is highly dependent of the nuclearity of the endogenous iron-sulfur cluster. Thus, from our point of view, in a cellular context, these results strengthen the argument that cellular sensitivity to radiation can also be due to loss of radiation-induced damage repair ability.

  10. Interactive effects of ultraviolet-B radiation and pesticide exposure on DNA photo-adduct accumulation and expression of DNA damage and repair genes in Xenopus laevis embryos.

    Science.gov (United States)

    Yu, Shuangying; Tang, Song; Mayer, Gregory D; Cobb, George P; Maul, Jonathan D

    2015-02-01

    Pesticide use and ultraviolet-B (UVB) radiation have both been suggested to adversely affect amphibians; however, little is known about their interactive effects. One potential adverse interaction could involve pesticide-induced dysregulation of DNA repair pathways, resulting in greater numbers of DNA photo-adducts from UVB exposure. In the present study, we investigated the interactive effects of UVB radiation and two common pesticides (endosulfan and α-cypermethrin) on induction of DNA photo-adducts and expression of DNA damage and repair related genes in African clawed frog (Xenopus laevis) embryos. We examined 13 genes that are, collectively, involved in stress defense, cell cycle arrest, nucleotide excision repair (NER), base excision repair, mismatch repair, DNA repair regulation, and apoptosis. We exposed X. laevis embryos to 0, 25, and 50 μg/L endosulfan or 0, 2.5, and 5.0 μg/L α-cypermethrin for 96 h, with environmentally relevant exposures of UVB radiation during the last 7 h of the 96 h exposure. We measured the amount of cyclobutane pyrimidine dimers (CPDs) and mRNA abundance of the 13 genes among treatments including control, pesticide only, UVB only, and UVB and pesticide co-exposures. Each of the co-exposure scenarios resulted in elevated CPD levels compared to UVB exposure alone, suggesting an inhibitory effect of endosulfan and α-cypermethrin on CPD repair. This is attributed to results indicating that α-cypermethrin and endosulfan reduced mRNA abundance of XPA and HR23B, respectively, to levels that may affect the initial recognition of DNA lesions. In contrast, both pesticides increased transcript abundance of CSA and MUTL. In addition, mRNA abundance of HSP70 and GADD45α were increased by endosulfan and mRNA abundance of XPG was increased by α-cypermethrin. XPC, HR23B, XPG, and GADD45α exhibited elevated mRNA concentrations whereas there was a reduction in MUTL transcript concentrations in UVB-alone treatments. It appeared that even

  11. Inter-individual variation in DNA double-strand break repair in human fibroblasts before and after exposure to low doses of ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, Paul F.; Nham, Peter B.; Urbin, Salustra S.; Hinz, John M.; Jones, Irene M. [Biosciences and Biotechnology Division, PO Box 808, L-452, Lawrence Livermore National Laboratory, Livermore, CA, 94551-0808 (United States); Thompson, Larry H., E-mail: thompson14@llnl.gov [Biosciences and Biotechnology Division, PO Box 808, L-452, Lawrence Livermore National Laboratory, Livermore, CA, 94551-0808 (United States)

    2010-01-05

    DNA double-strand breaks (DSB) are generally considered the most critical lesion induced by ionizing radiation (IR) and may initiate carcinogenesis and other disease. Using an immunofluorescence assay to simultaneously detect nuclear foci of the phosphorylated forms of histone H2AX and ATM kinase at sites of DSBs, we examined the response of 25 apparently normal and 10 DNA repair-deficient (ATM, ATR, NBN, LIG1, LIG4, and FANCG) primary fibroblast strains irradiated with low doses of {sup 137}Cs {gamma}-rays. Quiescent G{sub 0}/G{sub 1}-phase cultures were exposed to 5, 10, and 25 cGy and allowed to repair for 24 h. The maximum level of IR-induced foci (0.15 foci per cGy, at 10 or 30 min) in the normal strains showed much less inter-individual variation (CV {approx} 0.2) than the level of spontaneous foci, which ranged from 0.2-2.6 foci/cell (CV {approx} 0.6; mean {+-} SD of 1.00 {+-} 0.57). Significantly slower focus formation post-irradiation was observed in seven normal strains, similar to most mutant strains examined. There was variation in repair efficiency measured by the fraction of IR-induced foci remaining 24 h post-irradiation, curiously with the strains having slower focus formation showing more efficient repair after 25 cGy. Interestingly, the ranges of spontaneous and residual induced foci levels at 24 h in the normal strains were as least as large as those observed for the repair-defective mutant strains. The inter-individual variation in DSB foci parameters observed in cells exposed to low doses of ionizing radiation in this small survey of apparently normal people suggests that hypomorphic genetic variants in genomic maintenance and/or DNA damage signaling and repair genes may contribute to differential susceptibility to cancer induced by environmental mutagens.

  12. Influence of Double-Strand Break Repair on Radiation Therapy-Induced Acute Skin Reactions in Breast Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Mumbrekar, Kamalesh Dattaram [Division of Radiobiology and Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka (India); Fernandes, Donald Jerard [Department of Radiotherapy and Oncology, Shirdi Sai Baba Cancer Hospital and Research Centre, Kasturba Hospital, Manipal, Karnataka (India); Goutham, Hassan Venkatesh [Division of Radiobiology and Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka (India); Sharan, Krishna [Department of Radiotherapy and Oncology, Shirdi Sai Baba Cancer Hospital and Research Centre, Kasturba Hospital, Manipal, Karnataka (India); Vadhiraja, Bejadi Manjunath [Manipal Hospital, Bangalore, Karnataka (India); Satyamoorthy, Kapaettu [Division of Biotechnology, School of Life Sciences, Manipal University, Manipal, Karnataka (India); Bola Sadashiva, Satish Rao, E-mail: satishraomlsc@gmail.com [Division of Radiobiology and Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka (India)

    2014-03-01

    Purpose: Curative radiation therapy (RT)-induced toxicity poses strong limitations for efficient RT and worsens the quality of life. The parameter that explains when and to what extent normal tissue toxicity in RT evolves would be of clinical relevance because of its predictive value and may provide an opportunity for personalized treatment approach. Methods and Materials: DNA double-strand breaks and repair were analyzed by microscopic γ-H2AX foci analysis in peripheral lymphocytes from 38 healthy donors and 80 breast cancer patients before RT, a 2 Gy challenge dose of x-ray exposed in vitro. Results: The actual damage (AD) at 0.25, 3, and 6 hours and percentage residual damage (PRD) at 3 and 6 hours were used as parameters to measure cellular radiosensitivity and correlated with RT-induced acute skin reactions in patients stratified as non-overresponders (NOR) (Radiation Therapy Oncology Group [RTOG] grade <2) and overresponders (OR) (RTOG grade ≥2). The results indicated that the basal and induced (at 0.25 and 3 hours) γ-H2AX foci numbers were nonsignificant (P>.05) between healthy control donors and the NOR and OR groups, whereas it was significant between ORs and healthy donors at 6 hours (P<.001). There was a significantly higher PRD in OR versus NOR (P<.05), OR versus healthy donors (P<.001) and NOR versus healthy donors (P<.01), supported further by the trend analysis (r=.2392; P=.0326 at 6 hours). Conclusions: Our findings strongly suggest that the measurement of PRD by performing γ-H2AX foci analysis has the potential to be developed into a clinically useful predictive assay.

  13. Impaired Cytogenetic Damage Repair and Cell Cycle Regulation in Response to Ionizing Radiation in Human Fibroblast Cells with Individual Knock-down of 25 Genes

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry; Emami, Kamal; Hammond, Dianne; Casey, Rachael; Mehta, Satish; Jeevarajan, Antony; Pierson, Duane; Wu, Honglu

    2008-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have demonstrated that genes with upregulated expression induced by IR may play important roles in DNA damage sensing, cell cycle checkpoint and chromosomal repair, the relationship between the regulation of gene expression by IR and its impact on cytogenetic responses to ionizing radiation has not been systematically studied. In our present study, the expression of 25 genes selected based on their transcriptional changes in response to IR or from their known DNA repair roles were individually knocked down by siRNA transfection in human fibroblast cells. Chromosome aberrations (CA) and micronuclei (MN) formation were measured as the cytogenetic endpoints. Our results showed that the yield of MN and/or CA formation were significantly increased by suppressed expression of 5 genes that included Ku70 in the DSB repair pathway; XPA in the NER pathway; RPA1 in the MMR pathway; RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes including MRE11A, RAD51 in the DSB pathway, and SESN1 and SUMO1 showed significant inhibition of cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, p21 and MLH1 expression resulted in both enhanced cell cycle progression and significantly higher yield of cytogenetic damage, indicating the involvement of these gene products in both cell cycle control and DNA damage repair. Of these 11 genes that affected the cytogenetic response, 9 were up-regulated in the cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulating the biological consequences after IR. Failure to express these IR-responsive genes, such as by gene mutation, could seriously change the outcome of the post IR scenario and lead to carcinogenesis.

  14. Nicotinamide enhances repair of arsenic and ultraviolet radiation-induced DNA damage in HaCaT keratinocytes and ex vivo human skin.

    Directory of Open Access Journals (Sweden)

    Benjamin C Thompson

    Full Text Available Arsenic-induced skin cancer is a significant global health burden. In areas with arsenic contamination of water sources, such as China, Pakistan, Myanmar, Cambodia and especially Bangladesh and West Bengal, large populations are at risk of arsenic-induced skin cancer. Arsenic acts as a co-carcinogen with ultraviolet (UV radiation and affects DNA damage and repair. Nicotinamide (vitamin B3 reduces premalignant keratoses in sun-damaged skin, likely by prevention of UV-induced cellular energy depletion and enhancement of DNA repair. We investigated whether nicotinamide modifies DNA repair following exposure to UV radiation and sodium arsenite. HaCaT keratinocytes and ex vivo human skin were exposed to 2μM sodium arsenite and low dose (2J/cm2 solar-simulated UV, with and without nicotinamide supplementation. DNA photolesions in the form of 8-oxo-7,8-dihydro-2'-deoxyguanosine and cyclobutane pyrimidine dimers were detected by immunofluorescence. Arsenic exposure significantly increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine in irradiated cells. Nicotinamide reduced both types of photolesions in HaCaT keratinocytes and in ex vivo human skin, likely by enhancing DNA repair. These results demonstrate a reduction of two different photolesions over time in two different models in UV and arsenic exposed cells. Nicotinamide is a nontoxic, inexpensive agent with potential for chemoprevention of arsenic induced skin cancer.

  15. Nicotinamide enhances repair of arsenic and ultraviolet radiation-induced DNA damage in HaCaT keratinocytes and ex vivo human skin.

    Science.gov (United States)

    Thompson, Benjamin C; Halliday, Gary M; Damian, Diona L

    2015-01-01

    Arsenic-induced skin cancer is a significant global health burden. In areas with arsenic contamination of water sources, such as China, Pakistan, Myanmar, Cambodia and especially Bangladesh and West Bengal, large populations are at risk of arsenic-induced skin cancer. Arsenic acts as a co-carcinogen with ultraviolet (UV) radiation and affects DNA damage and repair. Nicotinamide (vitamin B3) reduces premalignant keratoses in sun-damaged skin, likely by prevention of UV-induced cellular energy depletion and enhancement of DNA repair. We investigated whether nicotinamide modifies DNA repair following exposure to UV radiation and sodium arsenite. HaCaT keratinocytes and ex vivo human skin were exposed to 2μM sodium arsenite and low dose (2J/cm2) solar-simulated UV, with and without nicotinamide supplementation. DNA photolesions in the form of 8-oxo-7,8-dihydro-2'-deoxyguanosine and cyclobutane pyrimidine dimers were detected by immunofluorescence. Arsenic exposure significantly increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine in irradiated cells. Nicotinamide reduced both types of photolesions in HaCaT keratinocytes and in ex vivo human skin, likely by enhancing DNA repair. These results demonstrate a reduction of two different photolesions over time in two different models in UV and arsenic exposed cells. Nicotinamide is a nontoxic, inexpensive agent with potential for chemoprevention of arsenic induced skin cancer.

  16. Orphan receptor TR3 enhances p53 transactivation and represses DNA double-strand break repair in hepatoma cells under ionizing radiation.

    Science.gov (United States)

    Zhao, Bi-xing; Chen, Hang-zi; Du, Xiao-dan; Luo, Jie; He, Jian-ping; Wang, Rong-hao; Wang, Yuan; Wu, Rong; Hou, Ru-rong; Hong, Ming; Wu, Qiao

    2011-08-01

    In response to ionizing radiation (IR)-induced DNA double-strand breaks (DSB), cells elicit an evolutionarily conserved checkpoint response that induces cell cycle arrest and either DNA repair or apoptosis, thereby maintaining genomic stability. DNA-dependent protein kinase (DNA-PK) is a central enzyme involved in DSB repair for mammalian cells that comprises a DNA-PK catalytic subunit and the Ku protein, which act as regulatory elements. DNA-PK also functions as a signaling molecule to selectively regulate p53-dependent apoptosis in response to IR. Herein, we demonstrate that the orphan nuclear receptor TR3 suppresses DSB repair by blocking Ku80 DNA-end binding activity and promoting DNA-PK-induced p53 activity in hepatoma cells. We find that TR3 interacts with Ku80 and inhibits its binding to DNA ends, which then suppresses DSB repair. Furthermore, TR3 is a phosphorylation substrate for DNA-PK and interacts with DNA-PK catalytic subunit in a Ku80-independent manner. Phosphorylated TR3, in turn, enhances DNA-PK-induced phosphorylation and p53 transcription activity, thereby enhancing IR-induced apoptosis in hepatoma cells. Together, our findings reveal novel functions for TR3, not only in DSB repair regulation but also in IR-induced hepatoma cell apoptosis, and they suggest that TR3 is a potential target for cancer radiotherapy.

  17. Nicotinamide Enhances Repair of Arsenic and Ultraviolet Radiation-Induced DNA Damage in HaCaT Keratinocytes and Ex Vivo Human Skin

    OpenAIRE

    Thompson, Benjamin C.; Halliday, Gary M.; Damian, Diona L

    2015-01-01

    Arsenic-induced skin cancer is a significant global health burden. In areas with arsenic contamination of water sources, such as China, Pakistan, Myanmar, Cambodia and especially Bangladesh and West Bengal, large populations are at risk of arsenic-induced skin cancer. Arsenic acts as a co-carcinogen with ultraviolet (UV) radiation and affects DNA damage and repair. Nicotinamide (vitamin B3) reduces premalignant keratoses in sun-damaged skin, likely by prevention of UV-induced cellular energy ...

  18. Nicotinamide Enhances Repair of Arsenic and Ultraviolet Radiation-Induced DNA Damage in HaCaT Keratinocytes and Ex Vivo Human Skin

    OpenAIRE

    Thompson, Benjamin C.; Halliday, Gary M.; Damian, Diona L.

    2015-01-01

    Arsenic-induced skin cancer is a significant global health burden. In areas with arsenic contamination of water sources, such as China, Pakistan, Myanmar, Cambodia and especially Bangladesh and West Bengal, large populations are at risk of arsenic-induced skin cancer. Arsenic acts as a co-carcinogen with ultraviolet (UV) radiation and affects DNA damage and repair. Nicotinamide (vitamin B3) reduces premalignant keratoses in sun-damaged skin, likely by prevention of UV-induced cellular energy ...

  19. Calmodulin Mediates DNA Repair Pathways Involving H2AX in Response to Low-Dose Radiation Exposure of RAW 264.7 Macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Smallwood, Heather S.; Lopez Ferrer, Daniel; Eberlein, P. Elis; Watson, David J.; Squier, Thomas C.

    2009-02-05

    Understanding the molecular mechanisms that modulate macrophage radioresistance is necessary for the development of effective radiation therapies, as tumor-associated macrophages promote both angiogenesis and matrix remodeling that, in turn, enhance metastasis. In this respect, we have identified a dose-dependent increase in the abundance of the calcium regulatory protein calmodulin (CaM) in RAW 264.7 macrophages upon irradiation. CaM overexpression results in increased macrophage survival following radiation exposure, acting to diminish the sensitivity to low-dose exposures. Increases in CaM abundance also result in an increase in the number of phosphorylated histone H2AX protein complexes associated with DNA repair following macrophage irradiation, with no change in the extent of double-stranded DNA damage. In comparison, when NFκB-dependent pathways are inhibited, through the expression of a dominant-negative IκB construct, there is no significant increase in phosphorylated H2AX upon irradiation. These results indicate that the molecular basis for the up-regulation of histone H2AX mediated DNA-repair pathways is not the result of nonspecific NFκB-dependent pathways or a specific threshold of DNA damage. Rather, increases in CaM abundance act to minimize the low-dose hypersensitivity to radiation to enhance macrophage radioresistance through processes that include the upregulation of DNA repair pathways involving histone protein H2AX phosphorylation.

  20. Dietary proanthocyanidins prevent ultraviolet radiation-induced non-melanoma skin cancer through enhanced repair of damaged DNA-dependent activation of immune sensitivity.

    Science.gov (United States)

    Katiyar, Santosh K; Pal, Harish C; Prasad, Ram

    2017-04-12

    Numerous plant products have been used to prevent and manage a wide variety of diseases for centuries. These products are now considered as promising options for the development of more effective and less toxic alternatives to the systems of medicine developed primarily in developed countries in the modern era. Grape seed proanthocyanidins (GSPs) are of great interest due to their anti-carcinogenic effects that have been demonstrated using various tumor models including ultraviolet (UV) radiation-induced non-melanoma skin cancer. In a pre-clinical mouse model supplementation of a control diet (AIN76A) with GSPs at concentrations of 0.2% and 0.5% (w/w) significantly inhibits the growth and multiplicity of UVB radiation-induced skin tumors. In this review, we summarize the evidence that this inhibition of UVB-induced skin tumor development by dietary GSPs is mediated by a multiplicity of coordinated effects including: (i) Promotion of the repair of damaged DNA by nuclear excision repair mechanisms, and (ii) DNA repair-dependent stimulation of the immune system following the functional activation of dendritic cells and effector T cells. Dietary GSPs hold promise for the development of an effective alternative strategy for the prevention of excessive solar UVB radiation exposure-induced skin diseases including the risk of non-melanoma skin cancer in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Experimental study of the effects of helium-neon laser radiation on repair of injured tendon

    Science.gov (United States)

    Xu, Yong-Qing; Li, Zhu-Yi; Weng, Long-Jiang; An, Mei; Li, Kai-Yun; Chen, Shao-Rong; Wang, Jian-Xin; Lu, Yu

    1993-03-01

    Despite extensive research into the biology of tendon healing, predictably restoring normal function to a digit after a flexor tendon laceration remains one of the most difficult problems facing the hand surgeon. The challenge of simultaneously achieving tendon healing while minimizing the peritendinous scar formation, which limits tendon gliding, has captured the attention of investigators for many years. It has been said that low-power density helium-neon laser radiation had effects on anti-inflammation, detumescence, progressive wound healing, and reducing intestinal adhesions. This experimental study aims at whether helium-neon laser can reduce injured tendon adhesions and improve functional recovery of the injured tendon. Fifty white Leghorn hens were used. Ten were randomly assigned as a normal control group, the other forty were used in the operation. After anesthetizing them with Amytal, a half of the profundus tendons of the second and third foretoes on both sides of the feet were cut. Postoperatively, the hens moved freely in the cages. One side of the toes operated on were randomly chosen as a treatment group, the other side served as an untreated control group. The injured tendon toes in the treatment group were irradiated for twenty minutes daily with a fiber light needle of helium-neon laser therapeutic apparatus (wavelength, 6328 angstroms) at a constant power density of 12.74 mW/cm2, the first exposure taking place 24 hours after the operation. The longest course of treatment was 3 weeks. The control group was not irradiated. At 3 days, 1, 2, 3, and 5 weeks after surgery, 8 hens were sacrificed and their tendons were examined. The experimental results: (1) active, passive flexion and tendon gliding functional recovery were significantly better in the treatment group (p tendon at the cut site were significantly smaller in the treatment group (p tendon adhesions were significantly lighter in the treatment group (p tendon extrinsic healing, reducing

  2. Interactive effects of ultraviolet-B radiation and pesticide exposure on DNA photo-adduct accumulation and expression of DNA damage and repair genes in Xenopus laevis embryos

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Shuangying, E-mail: shuangying.yu@ttu.edu [Department of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, 1207 S. Gilbert Dr., Lubbock, TX 79416 (United States); Tang, Song, E-mail: song.tang@usask.ca [Department of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, 1207 S. Gilbert Dr., Lubbock, TX 79416 (United States); Mayer, Gregory D., E-mail: greg.mayer@ttu.edu [Department of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, 1207 S. Gilbert Dr., Lubbock, TX 79416 (United States); Cobb, George P., E-mail: george_cobb@baylor.edu [Department of Environmental Science, Baylor University, One Bear Place #97266, Waco, TX 76798 (United States); Maul, Jonathan D., E-mail: jonathan.maul@ttu.edu [Department of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, 1207 S. Gilbert Dr., Lubbock, TX 79416 (United States)

    2015-02-15

    Highlights: • Interactive effects of UVB radiation-pesticide co-exposures were examined in frogs. • Responses included induction of DNA photo-adducts and DNA damage and repair genes. • Elevated DNA adduct levels occurred for co-exposures compared to UVB alone. • One mechanism is that pesticides may alter nuclear excision repair gene expression. - Abstract: Pesticide use and ultraviolet-B (UVB) radiation have both been suggested to adversely affect amphibians; however, little is known about their interactive effects. One potential adverse interaction could involve pesticide-induced dysregulation of DNA repair pathways, resulting in greater numbers of DNA photo-adducts from UVB exposure. In the present study, we investigated the interactive effects of UVB radiation and two common pesticides (endosulfan and α-cypermethrin) on induction of DNA photo-adducts and expression of DNA damage and repair related genes in African clawed frog (Xenopus laevis) embryos. We examined 13 genes that are, collectively, involved in stress defense, cell cycle arrest, nucleotide excision repair (NER), base excision repair, mismatch repair, DNA repair regulation, and apoptosis. We exposed X. laevis embryos to 0, 25, and 50 μg/L endosulfan or 0, 2.5, and 5.0 μg/L α-cypermethrin for 96 h, with environmentally relevant exposures of UVB radiation during the last 7 h of the 96 h exposure. We measured the amount of cyclobutane pyrimidine dimers (CPDs) and mRNA abundance of the 13 genes among treatments including control, pesticide only, UVB only, and UVB and pesticide co-exposures. Each of the co-exposure scenarios resulted in elevated CPD levels compared to UVB exposure alone, suggesting an inhibitory effect of endosulfan and α-cypermethrin on CPD repair. This is attributed to results indicating that α-cypermethrin and endosulfan reduced mRNA abundance of XPA and HR23B, respectively, to levels that may affect the initial recognition of DNA lesions. In contrast, both pesticides

  3. Rescue of Mitomycin C- or Psoralen-Inactivated Micrococcus Radiodurans by Additional Exposure to Radiation or Alkylating Agents

    DEFF Research Database (Denmark)

    Hansen, M. Trier

    1982-01-01

    The processing of damaged DNA was altered in a mitomycin C-sensitive mutant (mtcA) of Micrococcus radiodurans. Even though the mutant retained resistance to 254-nm UV radiation, it did not, in contrast to the wild-type strain, show any excessive DNA degradation or cell death when incubated...... with chloramphenicol after sublethal doses of either UV light or mitomycin C. The results suggest the constitutive synthesis of an enzyme system responsible for wild-type proficiency in the repair of mitomycin C-induced damage. An alternative system able to repair damage caused by mitomycin C was demonstrated...... in the mtcA background. In this strain, additional damage infficted upon the cellular DNA effected a massive rescue of cells previously inactivated by mitomycin C. Rescue was provoked by ionizing radiation, by UV light, or by simple alkylating agents. Cells treated with psoralen plus near-UV radiation could...

  4. Radiation Sensitivity of Human CD34(+) Cells Versus Peripheral Blood T Lymphocytes of Newborns and Adults: DNA Repair and Mutagenic Effects.

    Science.gov (United States)

    Vandevoorde, C; Vral, A; Vandekerckhove, B; Philippé, J; Thierens, H

    2016-06-01

    As hematopoietic stem and progenitor cells (HSPCs) self-renew throughout life, accumulation of genomic alterations can potentially give rise to radiation carcinogenesis. In this study we examined DNA double-strand break (DSB) induction and repair as well as mutagenic effects of ionizing radiation in CD34(+) cells and T lymphocytes from the umbilical cord of newborns. The age dependence of DNA damage repair end points was investigated by comparing newborn T lymphocytes with adult peripheral blood T lymphocytes. As umbilical cord blood (UCB) contains T lymphocytes that are practically all phenotypically immature, we examined the radiation response of separated naive (CD45RA(+)) and memory (CD45RO(+)) T lymphocytes. The number of DNA DSBs was assessed by microscopic scoring of γ-H2AX/53BP1 foci 0.5 h after low-dose radiation exposure, while DNA repair was studied by scoring the number of residual γ-H2AX/53BP1 foci 24 h after exposure. Mutagenic effects were studied by the cytokinesis block micronucleus (CBMN) assay. No significant differences in the number of DNA DSBs induced by low-dose (100-200 mGy) radiation were observed among the three different cell types. However, residual γ-H2AX/53BP1 foci levels 24 h postirradiation were significantly lower in CD34(+) cells compared to newborn T lymphocytes, while newborn T lymphocytes showed significantly higher foci yields than adult T lymphocytes. No significant differences in the level of radiation-induced micronuclei at 2 Gy were observed between CD34(+) cells and newborn T lymphocytes. However, newborn T lymphocytes showed a significantly higher number of micronuclei compared to adult T lymphocytes. These results confirm that CD34(+) cell quiescence promotes mutagenesis after exposure. Furthermore, we can conclude that newborn peripheral T lymphocytes are significantly more radiosensitive than adult peripheral T lymphocytes. Using the results from the comparative study of radiation-induced DNA damage repair end

  5. Mitotic regulator Nlp interacts with XPA/ERCC1 complexes and regulates nucleotide excision repair (NER) in response to UV radiation.

    Science.gov (United States)

    Ma, Xiao-Juan; Shang, Li; Zhang, Wei-Min; Wang, Ming-Rong; Zhan, Qi-Min

    2016-04-10

    Cellular response to DNA damage, including ionizing radiation (IR) and UV radiation, is critical for the maintenance of genomic fidelity. Defects of DNA repair often result in genomic instability and malignant cell transformation. Centrosomal protein Nlp (ninein-like protein) has been characterized as an important cell cycle regulator that is required for proper mitotic progression. In this study, we demonstrate that Nlp is able to improve nucleotide excision repair (NER) activity and protects cells against UV radiation. Upon exposure of cells to UVC, Nlp is translocated into the nucleus. The C-terminus (1030-1382) of Nlp is necessary and sufficient for its nuclear import. Upon UVC radiation, Nlp interacts with XPA and ERCC1, and enhances their association. Interestingly, down-regulated expression of Nlp is found to be associated with human skin cancers, indicating that dysregulated Nlp might be related to the development of human skin cancers. Taken together, this study identifies mitotic protein Nlp as a new and important member of NER pathway and thus provides novel insights into understanding of regulatory machinery involved in NER.

  6. Effect of chronic low dose natural radiation in human peripheral blood mononuclear cells: Evaluation of DNA damage and repair using the alkaline comet assay.

    Science.gov (United States)

    Kumar, P R Vivek; Seshadri, M; Jaikrishan, G; Das, Birajalaxmi

    2015-05-01

    This study investigates whether peripheral blood mononuclear cells (PBMCs) from inhabitants of Kerala in southwest India, exposed to chronic low dose natural radiation in vivo (>1 mSv year(-1)), respond with a radioadaptive response to a challenging dose of gamma radiation. Toward this goal, PBMCs isolated from 77 subjects from high-level natural radiation areas (HLNRA) and 37 subjects from a nearby normal level natural radiation area (NLNRA) were challenged with 2 Gy and 4 Gy gamma radiation. Subjects from HLNRA were classified based on the mean annual effective dose received, into low dose group (LDG) and high dose group (HDG) with mean annual effective doses of 2.69 mSv (N=43, range 1.07 mSv year(-1) to 5.55 mSv year(-1)) and 9.62 mSv (N = 34, range 6.07 mSv year(-1) to 17.41 mSv year(-1)), respectively. DNA strand breaks and repair kinetics (at 7 min, 15 min and 30 min after 4 Gy) were evaluated using the alkaline single cell gel electrophoresis (comet) assay. Initial levels of DNA strand breaks observed after either a 2 Gy or a 4 Gy challenging dose were significantly lower in subjects of the HDG from HLNRA compared to subjects of NLNRA (2 Gy, P = 0.01; 4 Gy, P = 0.02) and LDG (2 Gy P = 0.01; 4 Gy, P=0.05). Subjects of HDG from HLNRA showed enhanced rejoining of DNA strand breaks (HDG/NLNRA, P = 0.06) during the early stage of repair (within 7 min). However at later times a similar rate of rejoining of strand breaks was observed across the groups (HDG, LDG and NLNRA). Preliminary results from our study suggest in vivo chronic low-level natural radiation provides an initial exposure that allows an adaptation to a subsequent higher radiation exposure, perhaps through improving DNA repair via an unknown mechanism. Therefore, further investigations would be necessary in this population to understand the biological and health effects of chronic low-level natural radiation exposures. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Influence of 1.8-GHz (GSM) radiofrequency radiation (RFR) on DNA damage and repair induced by X-rays in human leukocytes in vitro.

    Science.gov (United States)

    Zhijian, Chen; Xiaoxue, Li; Yezhen, Lu; Deqiang, Lu; Shijie, Chen; Lifen, Jin; Jianlin, Lou; Jiliang, He

    2009-01-01

    In the present study, the in vitro comet assay was used to determine whether 1.8-GHz radiofrequency radiation (RFR) can influence DNA repair in human leukocytes exposed to X-rays. The specific energy absorption rate (SAR) of 2 W/kg (the current European safety limit) was applied. The leukocytes from four young healthy donors were intermittently exposed to RFR for 24 h (fields on for 5 min, fields off for 10 min), and then irradiated with X-rays at doses of 0.25, 0.5, 1.0 and 2.0 Gy. DNA damage to human leukocytes was detected using the comet assay at 0, 15, 45, 90, 150 and 240 min after exposure to X-rays. Using the comet assay, the percent of DNA in the tail (% tail DNA) served as the indicator of DNA damage; the DNA repair percentage (DRP) served as the indicator of the DNA repair speed. The results demonstrated that (1) the DNA repair speeds of human leukocytes after X-ray exposure exhibited individual differences among the four donors; (2) the intermittent exposures of 1.8-GHz RFR at the SAR of 2 W/kg for 24 h did not directly induce DNA damage or exhibit synergistic effects with X-rays on human leukocytes.

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

    Science.gov (United States)

    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.

  9. Normal repair of ultraviolet radiation-induced DNA damage in familial melanoma without CDKN2A or CDK4 gene mutation.

    Science.gov (United States)

    Shannon, J A; Matias, C; Luxford, C; Kefford, R F; Mann, G J

    1999-04-01

    Excessive sun exposure and family history are strong risk factors for the development of cutaneous melanoma. Inherited susceptibility to this type of skin cancer could therefore result from constitutively impaired capacity to repair ultraviolet (UV)-induced DNA lesions. While a proportion of familial melanoma kindreds exhibit germline mutations in the cell cycle regulatory gene CDKN2A (p16INK4a) or its protein target, cyclin-dependent kinase 4 (CDK4), the biochemical basis of most familial melanoma is unknown. We have examined lymphoblastoid cell lines from melanoma-affected and unaffected individuals from large hereditary melanoma kindreds which are not attributable to CDKN2A or CDK4 gene mutation. These lines were tested for sensitivity of clonogenic growth to UV radiation and for their ability to repair transfected UV-damaged plasmid templates (host cell reactivation). Two of seven affected-unaffected pairs differed in colony survival after exposure to UVB radiation; however, no significant differences were observed in the host-cell reactivation assays. These results indicate that melanoma susceptibility genes other than CDKN2A and CDK4 do not impair net capacity to repair UV-induced DNA damage.

  10. In normal human fibroblasts variation in DSB repair capacity cannot be ascribed to radiation-induced changes in the localisation, expression or activity of major NHEJ proteins

    DEFF Research Database (Denmark)

    Kasten-Pisula, Ulla; Vronskaja, Svetlana; Overgaard, Jens

    2008-01-01

    BACKGROUND AND PURPOSE: The aim of the present study was to test whether for normal human fibroblasts the variation in double-strand break (DSB) repair capacity results from radiation-induced differences in localisation, expression or activity of major non-homologous end-joining (NHEJ) proteins....... MATERIALS AND METHODS: Experiments were performed with 11 normal human fibroblast strains AF01-11. NHEJ proteins were determined by Western blot and DNA-PK activity by pulldown-assay. RESULTS: The four NHEJ proteins tested (Ku70, Ku80, XRCC4 and DNA-PKcs) were found to be localised almost exclusively...... in the activity of the DNA-PK complex induced upon irradiation. CONCLUSIONS: For normal human fibroblasts, the level or activity of NHEJ proteins measured prior to or after irradiation cannot be used to predict the DSB repair capacity or cellular radiosensitivity. Udgivelsesdato: 2008-Mar...

  11. Dipeptide Formation from Amino Acid Monomer Induced by keV Ion Irradiation: An Implication for Physicochemical Repair by Radiation Itself

    Institute of Scientific and Technical Information of China (English)

    WANG Wei; YUAN Hang; WANG Xiangqin; YU Zengliang

    2008-01-01

    An identification of Phe dipeptide from L-phenylalanine monomers after keV nitro-gen and argon ion implantation, by using the HPLC (high performance liquid chromatography) and LC-MS(liquid chromatography mass spectrometer) methods is reported. The results showed a similar yield behavior for both ion species, namely: 1) the yield of dipeptides under alkalescent conditions was distinctly higher than that under acidic or neutral conditions; 2) for different ion species, the dose-yield curves tracked a similar trend which was called a counter-saddle curve. The dipeptide formation may implicate a recombination repair mechanism of damaged biomolecules that energetic ions have left in their wake. Accordingly a physicochemical self-repair mechanism by radiation itself for the ion-beam radiobiological effects is proposed.

  12. [Radiation lesion formation and character of repair processes in the hematopoietic system of primates exposed to continuous and fractionated gamma-irradiation by equally effective doses].

    Science.gov (United States)

    Burkovskaia, T E; Shafirkin, A V; Petrov, V M; Shtemberg, A S; Chel'naia, N A; Ivanova, S M

    2012-01-01

    The article is dedicated to comparison of the biological effectiveness of continuous and fractionated gamma-irradiation of rhesus macaques by equally effective doses. These radiation conditions are broadly used in radiobiological experiments. Specifically, they are applied in modeling radiation effects on cosmonauts during extended exploration mission. A model of radiation damage and repair on the cell, tissue and organism levels, i.e., a model of effective residual dose responsible for change in mammals' resistance to irradiation of varying duration was used to calculate equally effective doses in the experiment with primates subject to continuous and fractionated exposure. The authors publish data related to formation of radiation lesion and rate of ensuing hemopoiesis reparation. Two groups of animals were compared in resistance modification followed after testing by acute irradiation. The test was to reproduce a radiation situation for cosmonauts in the event of a cannonade of powerful solar proton events resulting in an effective residual dose of 1 Sv total The experiment evidenced close resemblance of the hemopoietic effects in primates exposed to the compared radiation conditions.

  13. Recovery of Sublethally Injured Bacteria Using Selective Agar Overlays.

    Science.gov (United States)

    McKillip, John L.

    2001-01-01

    This experiment subjects bacteria in a food sample and an environmental sample to conditions of sublethal stress in order to assess the effectiveness of the agar overlay method to recover sublethally injured cells compared to direct plating onto the appropriate selective medium. (SAH)

  14. Modulation of RhoA GTPase Activity Sensitizes Human Cervix Carcinoma Cells to γ-Radiation by Attenuating DNA Repair Pathways

    Directory of Open Access Journals (Sweden)

    Juliana H. Osaki

    2016-01-01

    Full Text Available Radiotherapy with γ-radiation is widely used in cancer treatment to induce DNA damage reducing cell proliferation and to kill tumor cells. Although RhoA GTPase overexpression/hyperactivation is observed in many malignancies, the effect of RhoA activity modulation on cancer radiosensitivity has not been previously investigated. Here, we generated stable HeLa cell clones expressing either the dominant negative RhoA-N19 or the constitutively active RhoA-V14 and compared the responses of these cell lines with those of parental HeLa cells, after treatment with low doses of γ-radiation. HeLa-RhoA-N19 and HeLa-RhoA-V14 clones displayed reduced proliferation and survival compared to parental cells after radiation and became arrested at cell cycle stages correlated with increased cellular senescence and apoptosis. Also, Chk1/Chk2 and histone H2A phosphorylation data, as well as comet assays, suggest that the levels of DNA damage and DNA repair activation and efficiency in HeLa cell lines are correlated with active RhoA. In agreement with these results, RhoA inhibition by C3 toxin expression drastically affected homologous recombination (HR and nonhomologous end joining (NHEJ. These data suggest that modulation of RhoA GTPase activity impairs DNA damage repair, increasing HeLa cell radiosensitivity.

  15. Depletion of Histone Demethylase Jarid1A Resulting in Histone Hyperacetylation and Radiation Sensitivity Does Not Affect DNA Double-Strand Break Repair.

    Directory of Open Access Journals (Sweden)

    Corina Penterling

    Full Text Available Histone demethylases have recently gained interest as potential targets in cancer treatment and several histone demethylases have been implicated in the DNA damage response. We investigated the effects of siRNA-mediated depletion of histone demethylase Jarid1A (KDM5A, RBP2, which demethylates transcription activating tri- and dimethylated lysine 4 at histone H3 (H3K4me3/me2, on growth characteristics and cellular response to radiation in several cancer cell lines. In unirradiated cells Jarid1A depletion lead to histone hyperacetylation while not affecting cell growth. In irradiated cells, depletion of Jarid1A significantly increased cellular radiosensitivity. Unexpectedly, the hyperacetylation phenotype did not lead to disturbed accumulation of DNA damage response and repair factors 53BP1, BRCA1, or Rad51 at damage sites, nor did it influence resolution of radiation-induced foci or rejoining of reporter constructs. We conclude that the radiation sensitivity observed following depletion of Jarid1A is not caused by a deficiency in repair of DNA double-strand breaks.

  16. High radiation and desiccation tolerance of nitrogen-fixing cultures of the cyanobacterium Anabaena sp. strain PCC 7120 emanates from genome/proteome repair capabilities.

    Science.gov (United States)

    Singh, Harinder; Anurag, Kirti; Apte, Shree Kumar

    2013-10-12

    The filamentous nitrogen-fixing cyanobacterium, Anabaena sp. strain PCC 7120 was found to tolerate very high doses of (60)Co-gamma radiation or prolonged desiccation. Post-stress, cells remained intact and revived all the vital functions. A remarkable capacity to repair highly disintegrated genome and recycle the damaged proteome appeared to underlie such high radioresistance and desiccation tolerance. The close similarity observed between the cellular response to irradiation or desiccation stress lends strong support to the notion that tolerance to these stresses may involve similar mechanisms.

  17. Search for novel remedies to augment radiation resistance of inhabitants of Fukushima and Chernobyl disasters: identifying DNA repair protein XRCC4 inhibitors.

    Science.gov (United States)

    Sun, Mao-Feng; Chen, Hsin-Yi; Tsai, Fuu-Jen; Lui, Shu-Hui; Chen, Chih-Yi; Chen, Calvin Yu-Chian

    2011-10-01

    Two nuclear plant disasters occurring within a span of 25 years threaten health and genome integrity both in Fukushima and Chernobyl. Search for remedies capable of enhancing DNA repair efficiency and radiation resistance in humans appears to be a urgent problem for now. XRCC4 is an important enhancer in promoting repair pathway triggered by DNA double-strand break (DSB). In the context of radiation therapy, active XRCC4 could reduce DSB-mediated apoptotic effect on cancer cells. Hence, developing XRCC4 inhibitors could possibly enhance radiotherapy outcomes. In this study, we screened traditional Chinese medicine (TCM) database, TCM Database@Taiwan, and have identified three potent inhibitor agents against XRCC4. Through molecular dynamics simulation, we have determined that the protein-ligand interactions were focused at Lys188 on chain A and Lys187 on chain B. Intriguingly, the hydrogen bonds for all three ligands fluctuated frequently but were held at close approximation. The pi-cation interactions and ionic interactions mediated by o-hydroxyphenyl and carboxyl functional groups respectively have been demonstrated to play critical roles in stabilizing binding conformations. Based on these results, we reported the identification of potential radiotherapy enhancers from TCM. We further characterized the key binding elements for inhibiting the XRCC4 activities.

  18. Participation of different genes in the ruptures repair of double chain in Escherichia coli stumps exposed to gamma radiation; Participacion de diferentes genes en la reparacion de rupturas de doble cadena en cepas de Escherichia coli expuestas a radiacion gamma

    Energy Technology Data Exchange (ETDEWEB)

    Serment G, J. H.; Martinez M, E.; Alcantara D, D., E-mail: jorge.serment@inin.gob.mx [ININ, Departamento de Biologia, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2013-05-01

    All living organisms are naturally exposed to radiation from different sources. Ionizing radiation produces a plethora of lesions upon DNA that can be categorized as single and double strand breaks and base damage. Among them, unrepaired double strand breaks (Dbs) have the greatest biological significance, since they are responsible of cell death. In Escherichia coli this kind of lesions are repaired mostly by homologous recombination. In this work the participation of some recombination genes in the repair of Dbs is evaluated. Escherichia coli defective strains were exposed to gamma radiation and incubated for different periods in ideal conditions. Both micro electrophoresis and pulse field gel electrophoresis techniques were used to evaluate the kinetics of repair of such lesions, reflecting the importance of each defective gene in the process. (Author)

  19. A modified fluorimetric neutral filter elution method for analyzing radiation-induced double strand break and repair.

    Science.gov (United States)

    Goutham, Venkatesh H; Kamalesh, Mumbrekar D; Guruprasad, Parashiva K; Vadhiraja, Manjunath B; Satyamoorthy, Kapaettu; Rao Bola Satish, Sadashiva

    2011-07-15

    Neutral filter elution assay is one of the methods used for detection of DNA double strand breaks (DSBs). However, it is laborious, expensive, and hazardous (radiolabeled precursors for DSB detection and scintillation counter for quantification), making it a less preferred method for DSB detection. In the present study, an attempt was made to improve the existing neutral filter elution assay by making use of fluorescent dye (PicoGreen) and microfiltration assembly for eluting the fragmented DNA, thereby reducing the cost and time required for the assay. We studied the effect of dye dilution, pH conditions, and cell number as a part of method standardization. X-ray dose-response and repair kinetics in lymphocytes as well as cell lines were studied for validating the sensitivity of the assay. A linear dose-response relationship for DSBs was observed at a cell number of 4×10(5)cells, a dye dilution of 500-fold, and at pH 10. Repair kinetics revealed a time-dependent repair of DSBs up to 360 min of posttreatment, indicating its usefulness in DSB repair studies. In conclusion, the present modified method is more efficient (in terms of cell number), cost effective, less time-consuming, and less hazardous compared to the existing method. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. [Principles of a canteen feeding organization of railway transport workers in repair-restorative work in regions polluted with radiation].

    Science.gov (United States)

    Istomin, A V; Zhiliaev, N S

    1997-01-01

    Dietary intake and actual food consumption of the railway transport workers are employed in repair in radioactive polluted regions. Disbalance of dining rations and deficiency in vegetable fat, some mineral elements and vitamins was established. For the correction of revealed defects the methodological recommendations for organization of a canteen feeding of the workers of railway transport was developed.

  1. Interactive Effects of Temperature and UV Radiation on Photosynthesis of Chlorella Strains from Polar, Temperate and Tropical Environments: Differential Impacts on Damage and Repair.

    Science.gov (United States)

    Wong, Chiew-Yen; Teoh, Ming-Li; Phang, Siew-Moi; Lim, Phaik-Eem; Beardall, John

    2015-01-01

    Global warming and ozone depletion, and the resulting increase of ultraviolet radiation (UVR), have far-reaching impacts on biota, especially affecting the algae that form the basis of the food webs in aquatic ecosystems. The aim of the present study was to investigate the interactive effects of temperature and UVR by comparing the photosynthetic responses of similar taxa of Chlorella from Antarctic (Chlorella UMACC 237), temperate (Chlorella vulgaris UMACC 248) and tropical (Chlorella vulgaris UMACC 001) environments. The cultures were exposed to three different treatments: photosynthetically active radiation (PAR; 400-700 nm), PAR plus ultraviolet-A (320-400 nm) radiation (PAR + UV-A) and PAR plus UV-A and ultraviolet-B (280-320 nm) radiation (PAR + UV-A + UV-B) for one hour in incubators set at different temperatures. The Antarctic Chlorella was exposed to 4, 14 and 20°C. The temperate Chlorella was exposed to 11, 18 and 25°C while the tropical Chlorella was exposed to 24, 28 and 30°C. A pulse-amplitude modulated (PAM) fluorometer was used to assess the photosynthetic response of microalgae. Parameters such as the photoadaptive index (Ek) and light harvesting efficiency (α) were determined from rapid light curves. The damage (k) and repair (r) rates were calculated from the decrease in ΦPSIIeff over time during exposure response curves where cells were exposed to the various combinations of PAR and UVR, and fitting the data to the Kok model. The results showed that UV-A caused much lower inhibition than UV-B in photosynthesis in all Chlorella isolates. The three isolates of Chlorella from different regions showed different trends in their photosynthesis responses under the combined effects of UVR (PAR + UV-A + UV-B) and temperature. In accordance with the noted strain-specific characteristics, we can conclude that the repair (r) mechanisms at higher temperatures were not sufficient to overcome damage caused by UVR in the Antarctic Chlorella strain

  2. Sublethal haematological effects of zinc on the freshwater fish ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-06-17

    Jun 17, 2008 ... Department of Animal and Environmental Biology, Delta State University, ... exposure of a freshwater fish, Heteroclarias sp. to sublethal concentrations (5.0 .... Spain). Red and white blood cell counts were counted under light.

  3. Avoidance behaviour and anxiety in rats irradiated with a sublethal dose of gamma-rays.

    Science.gov (United States)

    Tomášová, Lenka; Smajda, B; Bona, M

    2011-12-01

    The aim of this study was to assess, whether a sublethal dose of gamma-rays will influence the avoidance behaviour and anxiety in rats and whether the response to radiation depends on time of day of its application. Adult male Wistar rats were tested in elevated plus-maze, in hot plate test and in the light/dark box in 4 regular intervals during a day. After two weeks the animals were irradiated with a whole-body dose 6 Gy of gamma-rays. One day after irradiation the animals were repeatedly tested in the same way, as before irradiation. In the plus-maze test an increased level of anxiety was established. The irradiation significantly decreased the locomotor activity of rats, but the extent of exploratory and comfortable behaviour were not altered. After irradiation, an elevated aversion to the thermal stimulus was observed in the hot plate test. The effects of radiation were more pronounced in the light period of the day, than in the dark one. No significant differences in aversion to light were detected after irradiation. The obtained results indicate, that sublethal doses of ionizing radiation can markedly influence the reactivity of animals to adverse stimuli, their motoric activity and emotional status, as well.

  4. Radiation damage and repair in cells and cell components. Progress report, November 1, 1977--October 31, 1978. [Uv and x radiation, bacteriophages

    Energy Technology Data Exchange (ETDEWEB)

    Fluke, D.J.; Pollard, E.C.

    1978-01-01

    Progress is reported on the following research projects: coordinate induction of mutagenesis, radioresistance, and inhibition of post-radiation DNA degradation; radioinduced filamentation; action spectrum for induction of K12 lambda phage; effects of uv radiation on cells in the frozen state; dependence of mutagenesis on wavelength of uv; and w-reactivation of x-irradiated phage lambda. (HLW)

  5. Radio-adaptive response of base excision repair genes and proteins in human peripheral blood mononuclear cells exposed to gamma radiation.

    Science.gov (United States)

    Toprani, Sneh M; Das, Birajalaxmi

    2015-09-01

    Radio-adaptive response is a mechanism whereby a low-dose exposure (priming dose) induces resistance to a higher dose (challenging dose) thus significantly reducing its detrimental effects. Radiation-induced DNA damage gets repaired through various DNA repair pathways in human cells depending upon the type of lesion. The base excision repair (BER) pathway repairs radiation-induced base damage, abasic sites and single-strand breaks in cellular DNA. In the present study, an attempt has been made to investigate the involvement of BER genes and proteins in the radio-adaptive response in human resting peripheral blood mononuclear cells (PBMC). Venous blood samples were collected from 20 randomly selected healthy male individuals with written informed consent. PBMC were isolated and irradiated at a priming dose of 0.1 Gy followed 4h later with a challenging dose of 2.0 Gy (primed cells). Quantitation of DNA damage was done using the alkaline comet assay immediately and expression profile of BER genes and proteins were studied 30 min after the challenging dose using real-time quantitative polymerase chain reaction and western blot, respectively. The overall result showed significant (P ≤ 0.05) reduction of DNA damage in terms of percentage of DNA in tail (%T) with a priming dose of 0.1 Gy followed by a challenging dose of 2.0 Gy after 4 h. Twelve individuals showed significant (P ≤ 0.05) reduction in %T whereas eight individuals showed marginal reduction in DNA damage that was not statistically significant. However, at the transcriptional level, BER genes such as APE1, FEN1 and LIGASE1 showed significant (P ≤ 0.05) up-regulation in both groups. Significant (P ≤ 0.05) up-regulation was also observed at the protein level for OGG1, APE1, MBD4, FEN1 and LIGASE1 in primed cells. Up-regulation of some BER genes and proteins such as APE1, FEN1 and LIGASE1 in primed cells of resting PBMC is suggestive of active involvement of the BER pathway in radio-adaptive response.

  6. Are genetic polymorphisms in OGG1, XRCC1 and XRCC3 genes predictive for the DNA strand break repair phenotype and genotoxicity in workers exposed to low dose ionising radiations?

    Energy Technology Data Exchange (ETDEWEB)

    Aka, Peter [Laboratory for Cell Genetics, Department of Biology, Free University of Brussels, Pleinlaan 2, B-1050 Brussels (Belgium)]. E-mail: paka@vub.ac.be; Mateuca, Raluca [Laboratory for Cell Genetics, Department of Biology, Free University of Brussels, Pleinlaan 2, B-1050 Brussels (Belgium); Buchet, Jean-Pierre [Unit of Industrial Toxicology and Occupational Medicine, Catholic University of Louvain, Clos Chapelle, Aux-Champs, B-1200 Brussels (Belgium); Thierens, Hubert [Department of Biomedical Physics and Radiation Protection, University of Ghent, Proeftuinstraat 86, B-9000 Ghent (Belgium); Kirsch-Volders, Micheline [Laboratory for Cell Genetics, Department of Biology, Free University of Brussels, Pleinlaan 2, B-1050 Brussels (Belgium)

    2004-11-22

    Identification of higher risk individuals carrying genetic polymorphisms responsible for reduced DNA repair capacity has substantial preventive implications as these individuals could be targeted for cancer prevention. We have conducted a study to assess the predictivity of the OGG1, XRCC1 and XRCC3 genotypes and the in vitro single strand break repair phenotype for the induction of genotoxic effects. At the population level, a significant contribution of the OGG1 genotypes to the in vitro DNA strand break repair capacity was found. At an individual level, the OGG1 variants Ser/Cys and Cys/Cys genotypes showed a slower in vitro DNA repair than the Ser/Ser OGG1genotype. A multivariate analysis performed with genotypes, age, cumulative dose, exposure status and smoking as independent variables indicated that in the control population, repair capacity is influenced by age and OGG1 polymorphisms. In the exposed population, DNA damage is greater in older men and in smokers. Repair capacity is slower in individuals with Ser/Cys or Cys/Cys OGG1 genotypes compared to those with the Ser/Ser OGG1 genotype. Micronuclei (MN) frequencies increased with age and the cumulative dose of {gamma}-rays. Analysis of the total population revealed that genetic polymorphisms in XRCC1 resulted in higher residual DNA (RDNA) values and the Met/Met variant of XRCC3 resulted in an increased frequency of micronuclei. The analysis confirms that MN frequencies are reliable biomarkers for the assessment of genetic effects in workers exposed to ionising radiation (IR). A combined analysis of the three genotypes, OGG1, XRCC1 and XRCC3 polymorphisms is advised in order to assess individual susceptibility to ionising radiation. As an alternative or complement, the in vitro DNA strand break repair phenotype which integrates several repair pathways is recommended. Smokers with OGG1 polymorphisms who are exposed to ionising radiation represent a specific population requiring closer medical surveillance

  7. Thermal radiosensitization in radiation-sensitive mutant mouse leukemic cells

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Toshikazu (Hiroshima Univ. (Japan). School of Dentistry)

    1994-06-01

    This study investigated thermal, radiation, and combined thermal radiation sensitization of mouse leukemic cells, L5178Y, and radiation-sensitive mutant cells, LX830. Radiation sensitivity (D[sub 0]) values were 0.41 Gy for LX830 and 1.39 Gy for L5178Y, with the ratio of D[sub 0] values in LX830 to in L5178Y being 3.4. Thus, LX830 was more radiosensitive than L5178Y. LX830 showed no shouldered survival curves. Although sublethal damage (SLD) repair was seen to the almost same degree in both LX830 and L5178Y, potential lethal damage (PLD) repair was scarcely observed in LX830. Both cell lines were similar in thermal sensitivity (T[sub 0]). Eosine staining suggested that cell killing due to hyperthermia had occurred in the interphase in both LX830 and L5178Y. L5178Y showed thermal sensitivity low in the G1 phase and high in the S phase; on the contrary, LX830 showed it high in the G1 phase and low in the S phase. Thermal radiosensitization was similar in both cell lines, although there was a great difference in radiation sensitivity between the cell lines. The difference in radiation sensitivity (D[sub 0]) between L5178Y and LX830 became small when radiation was given at the time of the maximum thermal resistance. This seemed to contribute to a decrease in radiation sensitivity in LX830. It can be concluded that thermal radiosensitization depends on thermal sensitivity and that radiation sensitivity decreases in radiation-sensitive cells when exposed to irradiation at the time of thermal resistance. (N.K.).

  8. The influence of the wavelength of ultraviolet radiation on survival, mutation induction and DNA repair in irradiated Chinese hamster cells

    NARCIS (Netherlands)

    Zelle, B.; Reynolds, R.J.; Kottenhagen, M.J.; Schuite, A.; Lohman, P.H.M.

    1980-01-01

    Chinese hamster ovary cells were used to compare the cytotoxicity and mutagenicity of far-UV radiation emitted by a low-pressure mercury, germicidal lamp (wavelength predominantly 254 nm) with that of near-UV radiation emitted by a fluorescent lamp with a continuous spectrum (Westinghouse 'Sun

  9. Individual repair of radiation-induced DNA double-strand breaks in lymphocytes. Implications for radiation-induced dermatitis in breast cancer; Die individuelle Reparatur von strahleninduzierten DNA-Doppelstrangbruechen in Lymphozyten. Implikationen fuer die radiogene Dermatitis beim Mammakarzinom

    Energy Technology Data Exchange (ETDEWEB)

    Melchior, Patrick Wilhelm

    2011-07-01

    Purpose: Adjuvant 'whole breast radiotherapy' (WBRT) is the standard of care after breast conserving surgery in women with breast cancer. Throughout different cancer stages the addition of WBRT leads to significantly improved rates of freedom from local failure and overall survival. WBRT is generally well tolerated. A 5-10%-rate of severe acute or long-term side effects is commonly observed. For both radiation-mediated tumor-cell-elimination and induction of side effects, DNA-double-strand-breaks (DSB) presumably play the decisive role. The intensity of normal tissue reactions in radiotherapy can, in part, be attributed to the intrinsic DSB repair-capacity. In this study in vivo and in vitro experiments are carried through in order to assess DSB repair-kinetics in blood lymphocytes of women with breast cancer. These findings are to be correlated with the degree of radiation-induced normal tissue toxicity. Patients and Methods: Eighteen patients with breast cancer, in whom WBRT was indicated, were examined. A total WBRT dose of 50 Gy (single dose 2 Gy) with an additional boost-radiotherapy to the initial tumor-region to a total dose of 60-66 Gy was administered. DSB repair was determined by means of counting γ-H2AX foci in blood lymphocytes at predefined points in time, i.e. before and 0.5 h; 2.5 h; 5 h and 24 h after in vivo irradiation (1st fraction of WBRT) and before and 0.5 h; 2.5 h and 5 h after in vitro irradiation with increasing radiation doses in the range of 10 - 500 mGy. Acute normal tissue toxicity was scored on the basis of a modified RTOG-classification (main aspects were erythema and dry or moist skin desquamation). Results: DSB repair-halflife-times did not differ between patients with a higher or lower than average incidence of acute side effects. In patients with 'above average' side effects larger irradiation volumes were treated (volume surrounded by the 50%-isodose). Adjusted for these, no single patients showed elevated

  10. Endonuclease IV Is the Main Base Excision Repair Enzyme Involved in DNA Damage Induced by UVA Radiation and Stannous Chloride

    Directory of Open Access Journals (Sweden)

    Ellen S. Motta

    2010-01-01

    Full Text Available Stannous chloride (SnCl2 and UVA induce DNA lesions through ROS. The aim of this work was to study the toxicity induced by UVA preillumination, followed by SnCl2 treatment. E. coli BER mutants were used to identify genes which could play a role in DNA lesion repair generated by these agents. The survival assays showed (i The nfo mutant was the most sensitive to SnCl2; (ii lethal synergistic effect was observed after UVA pre-illumination, plus SnCl2 incubation, the nfo mutant being the most sensitive; (iii wild type and nfo mutants, transformed with pBW21 plasmid (nfo+ had their survival increased following treatments. The alkaline agarose gel electrophoresis assays pointed that (i UVA induced DNA breaks and fpg mutant was the most sensitive; (ii SnCl2-induced DNA strand breaks were higher than those from UVA and nfo mutant had the slowest repair kinetics; (iii UVA+SnCl2 promoted an increase in DNA breaks than SnCl2 and, again, nfo mutant displayed the slowest repair kinetics. In summary, Nfo protects E. coli cells against damage induced by SnCl2 and UVA+ SnCl2.

  11. Ionizing radiation-induced DNA damage and its repair in human cells. Final performance report, July 1992--June 1995

    Energy Technology Data Exchange (ETDEWEB)

    Dizdaroglu, M.

    1995-12-31

    The studies of DNA damage in living cells in vitro and in vivo were continued. A variety of systems including cultured mammalian cells, animals, and human tissues were used to conduct these studies. In addition, enzymatic repair of DNA base damage was studied using several DNA glycosylases. To this end, substrate specificities of these enzymes were examined in terms of a large number of base lesions in DNA. In the first phase of the studies, the author sought to introduce improvements to his methodologies for measurement of DNA damage using the technique of gas chromatography/mass spectrometry (GC/MS). In particular, the quantitative measurement of DNA base damage and DNA-protein crosslinks was improved by incorporation of isotope-dilution mass spectrometry into the methodologies. This is one of the most accurate techniques for quantification of organic compounds. Having improved the measurement technique, studies of DNA damage in living cells and DNA repair by repair enzymes were pursued. This report provides a summary of these studies with references to the original work.

  12. DNA damage induction and/or repair as mammalian cell biomarker for the prediction of cellular radiation response

    Science.gov (United States)

    Baumstark-Khan, C.

    DNA damage and its repair processes are key factors in cancer induction and also in the treatment of malignancies. Cancer prevention during extended space missions becomes a topic of great importance for space radiobiology. The knowledge of individual responsiveness would allow the protection strategy to be tailored optimally in each case. Radiobiological analysis of cultured cells derived from tissue explants from individuals has shown that measurement of the surviving fraction after 2 Gy (SF2) may be used to predict the individual responsiveness. However, clonogenic assays are timeconsuming, thus alternative assays for the determination of radiore-sponse are being sought. For that reason CHO cell strains having different repair capacities were used for examining whether DNA strand break repair is a suitable experimental design to allow predictive statements. Cellular survival (CFA assay) and DNA strand breaks (total DNA strand breaks: FADU technique; DSBs: non-denaturing elution) were determined in parallel immediately after irradiation as well as after a 24 hour recovery period according to dose. There were no correlations between the dose-response curves of the initial level of DNA strand breaks and parameters that describe clonogenic survival curves (SF2). A good correlation exists between intrinsic cellular radioresistance and the extent of residual DNA strand breaks.

  13. Transplantation of bone marrow stromal cells overexpressing human vascular endothelial growth factor 165 enhances tissue repair in a rat model of radiation-induced injury

    Institute of Scientific and Technical Information of China (English)

    Wang Tao; Liao Tian'an; Wang Hong; Deng Wei; Yu Dahai

    2014-01-01

    Background The multilineage differentiation potential ability of bone marrow stromal cells (BMSCs) showed great potential in tissue engineering,while vascular endothelial growth factor 165 (VEGF165) promotes vasculogenesis and further promotes tissue regeneration.This study aimed to assess the ability of rat BMSCs expressing human VEGFA165 (hVEGF165) to promote tissue repair in rat model of radiation-induced injury.Methods Rat BMSCs were isolated from the tibia.Plasmid DNA expressing hVEGF165 was stably transfected into BMSCs using liposomes.The right hindlimb muscle of 40 rats was irradiated using a 60Co y source (total dose 30 Gy).The animals were divided into four groups (n=10):not injected with BMSCs (control; group 1) or intramuscularly injected two times (once in 2 weeks) with pcDNATM3.1-transfected BMSCs (group 2),untransfected BMSCs (group 3),or hVEGF165-transfected BMSCs (group 4).Angiography was performed 1 week after the last injection of BMSCs; samples of the hindlimb muscle were subjected to transmission electron microscopy,ultrastructural analysis,reverse transcription-PCR (RT-PCR),Western blotting,and immunohistochemistry.Results Rat BMSCs with multipotent differentiation capacity were isolated,hVEGF165-transfected BMSCs overexpressed hVEGF165 mRNA and protein.Injection of BMSCs (groups 2-4) increased the average vessel number,density,diameter,and cross-sectional area; mRNA expression of the myogenic markers including myoblast determination protein,myogenin,and α-smooth muscle actin; and CD31 protein expression; and promoted the repair of blood vessels and myofibers after radiation-induced injury compared to group 1; each of these parameters and hVEGF165 mRNA or protein expression were markedly improved in rats injected with hVEGF165-transfected BMSCs compared to groups 2 and 3.Conclusions BMSCs expressing hVEGF165 enhanced the repair of radiation-induced tissue injury by promoting vasculogenesis and muscle fiber regeneration.BMSCs expressing h

  14. Gene Expression of Hematoregulatory Cytokines is Elevated Endogenously After Sublethal Gamma Irradiation and is Differentially Enhanced by Therapeutic Administration of Biologic Response Modifiers

    Science.gov (United States)

    1994-01-01

    reconstitution of medullary Days After Irradiation and extramedullary hematopoiesis after sublethal irradia- FIGURE 7. Comparative elects of BRMs on 30-day...stimulating factor on recovery from radiation-induced hcmopoi,:tic Other studies have documented the absence of myeloid aplasia . EAp. henatoL 21:33W

  15. Impact of 1.8-GHz radiofrequency radiation (RFR) on DNA damage and repair induced by doxorubicin in human B-cell lymphoblastoid cells.

    Science.gov (United States)

    Zhijian, Chen; Xiaoxue, Li; Yezhen, Lu; Shijie, Chen; Lifen, Jin; Jianlin, Lou; Deqiang, Lu; Jiliang, He

    2010-01-01

    In the present in vitro study, a comet assay was used to determine whether 1.8-GHz radiofrequency radiation (RFR, SAR of 2W/kg) can influence DNA repair in human B-cell lymphoblastoid cells exposed to doxorubicin (DOX) at the doses of 0microg/ml, 0.05microg/ml, 0.075microg/ml, 0.10microg/ml, 0.15microg/ml and 0.20microg/ml. The combinative exposures to RFR with DOX were divided into five categories. DNA damage was detected at 0h, 6h, 12h, 18h and 24h after exposure to DOX via the comet assay, and the percent of DNA in the tail (% tail DNA) served as the indicator of DNA damage. The results demonstrated that (1) RFR could not directly induce DNA damage of human B-cell lymphoblastoid cells; (2) DOX could significantly induce DNA damage of human B-cell lymphoblastoid cells with the dose-effect relationship, and there were special repair characteristics of DNA damage induced by DOX; (3) E-E-E type (exposure to RFR for 2h, then simultaneous exposure to RFR and DOX, and exposure to RFR for 6h, 12h, 18h and 24h after exposure to DOX) combinative exposure could obviously influence DNA repair at 6h and 12h after exposure to DOX for four DOX doses (0.075microg/ml, 0.10microg/ml, 0.15microg/ml and 0.20microg/ml) in human B-cell lymphoblastoid cells. Copyright 2009 Elsevier B.V. All rights reserved.

  16. Dose response and adaptive response of non-homologous end joining repair genes and proteins in resting human peripheral blood mononuclear cells exposed to γ radiation.

    Science.gov (United States)

    Shelke, Shridevi; Das, Birajalaxmi

    2015-05-01

    Ionising radiation induces single-strand breaks, double-strand breaks (DSB) and base damages in human cell. DSBs are the most deleterious and if not repaired may lead to genomic instability and cell death. DSB can be repaired through non-homologous end joining (NHEJ) pathway in resting lymphocytes. In this study, NHEJ genes and proteins were studied in irradiated human peripheral blood mononuclear cells (PBMC) at resting stage. Dose-response, time point kinetics and adaptive-response studies were conducted in irradiated PBMC at various end points such as DNA damage quantitation, transcription and protein expression profile. Venous blood samples were collected from 20 random, normal and healthy donors with written informed consent. PBMC was separated and irradiated with various doses between 0.1 and 2.0 Gy ((60)CO-γ source) for dose-response study. Repair kinetics of DNA damage and time point changes in expression of genes and proteins were studied in post-irradiated PBMC at 2.0 Gy at various time points up to 240 min. Adaptive-response study was conducted with a priming dose of 0.1 Gy followed by a challenging dose of 2.0 Gy after 4-h incubation. Our results revealed that Ku70, Ku80, XLF and Ligase IV were significantly upregulated (P Adaptive-response study showed significantly increased expression of the proteins involved in NHEJ, suggesting their role in adaptive response in human PBMC at G0/G1, which has important implications to human health. © The Author 2014. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Adaptive response in mouse bone-marrow stromal cells exposed to 900-MHz radiofrequency fields: Gamma-radiation-induced DNA strand breaks and repair.

    Science.gov (United States)

    Ji, Yongxin; He, Qina; Sun, Yulong; Tong, Jian; Cao, Yi

    2016-01-01

    The aim of this study was to examine whether radiofrequency field (RF) preexposure induced adaptive responses (AR) in mouse bone-marrow stromal cells (BMSC) and the mechanisms underlying the observed findings. Cells were preexposed to 900-MHz radiofrequency fields (RF) at 120 μW/cm(2) power intensity for 4 h/d for 5 d. Some cells were subjected to 1.5 Gy γ-radiation (GR) 4 h following the last RF exposure. The intensity of strand breaks in the DNA was assessed immediately at 4 h. Subsequently, some BMSC were examined at 30, 60, 90, or 120 min utilizing the alkaline comet assay and γ-H2AX foci technique. Data showed no significant differences in number and intensity of strand breaks in DNA between RF-exposed and control cells. A significant increase in number and intensity of DNA strand breaks was noted in cells exposed to GR exposure alone. RF followed by GR exposure significantly decreased number of strand breaks and resulted in faster kinetics of repair of DNA strand breaks compared to GR alone. Thus, data suggest that RF preexposure protected cells from damage induced by GR. Evidence indicates that in RF-mediated AR more rapid repair kinetics occurs under conditions of GR-induced damage, which may be attributed to diminished DNA strand breakage.

  18. Radioprotection of mice by lactoferrin against irradiation with sublethal X-rays.

    Science.gov (United States)

    Nishimura, Yoshikazu; Homma-Takeda, Shino; Kim, Hee-Sun; Kakuta, Izuru

    2014-03-01

    The influence of a host defense protein, lactoferrin (LF), contained in exocrine secretions such as milk, on radiation disorder was investigated. A total of 25 C3H/He mice in each of two groups were maintained with 0.1% LF-added and LF-free diets, respectively, for one month. The mice were then treated with single whole-body X-ray irradiation at a sublethal dose (6.8 Gy), and the survival rate after irradiation was investigated. The survival rate at 30 d after irradiation was relatively higher in the LF group than in the control group (LF-free), (85 and 62%, respectively). The body weight 15 d after X-ray irradiation was also significantly greater in the LF group than in the control group. The hemoglobin level and hematocrit value were higher in the LF group at 5 d before X-ray irradiation. Another 52 mice underwent whole-body X-ray irradiation at the sublethal dose (6.8 Gy), and then LF was intraperitoneally injected once at 4 mg/animal to half of them. The survival rate in LF-treated mice 30 d after irradiation was 92%, significantly higher than in mice treated with saline (50%) (P = 0.0012). In addition, LF showed hydroxyl radical scavenger activity in vitro. These findings suggest that LF may inhibit radiation damage.

  19. Impairment of the non-homologous end joining and homologous recombination pathways of DNA double strand break repair: Impact on spontaneous and radiation-induced mammary and intestinal tumour risk in Apc min/+ mice.

    Science.gov (United States)

    Haines, Jackie W; Coster, Margaret; Bouffler, Simon D

    2015-11-01

    Female Apc(min/+) mice carrying the BALB/c variant of Prkdc or heterozygous knockout for Xrcc2, were sham- or 2 Gy X-irradiated as adults to compare the effect of mild impairments of double-strand break (DSB) repair pathways, non-homologous end joining (NHEJ) and homologous recombination (HR) respectively on spontaneous and radiation-induced mammary and intestinal tumorigenesis. Mice with impaired NHEJ showed no difference in incidence of spontaneous mammary tumours, compared with matched controls, (2.46 fold, P=0.121) and significantly less following irradiation (radiation-induced excess; 0.35 fold, P=0.008). In contrast mice with impaired HR presented with significantly less spontaneous mammary tumours than matched controls (0.33 fold, P=0.027) and significantly more following irradiation (radiation-induced excess; 3.3 fold, P=0.016). Spontaneous and radiation-induced intestinal adenoma multiplicity in the same groups were significantly greater than matched controls for mice with impaired NHEJ (sham; 1.29 fold, P<0.001, radiation-induced excess; 2.55 fold, P<0.001) and mice with impaired HR showed no significant differences (sham; 0.92 fold, P=0.166, radiation-induced excess; 1.16, P=0.274). Genetic insertion events were common in spontaneous tumours from NHEJ impaired mice compared with matched controls. γH2AX foci analysis suggests a significantly faster rate of DSB repair (MANOVA P<0.001) in intestinal than mammary tissue; apoptosis was also higher in irradiated intestine. To conclude, results suggest that pathway of choice for repair of spontaneous and radiation-induced DSBs is influenced by tissue type. NHEJ appears to play a greater role in DSB repair in intestinal tissue since impairment by functional change of Prkdc significantly increases the rate of mis-repair in intestinal but not mammary tissue. HR appears to play a greater role in DSB repair in adult mammary tissue since impaired HR results in significant changes in mammary but not in the intestinal

  20. Role of Artemis in DSB repair and guarding chromosomal stability following exposure to ionizing radiation at different stages of cell cycle

    Energy Technology Data Exchange (ETDEWEB)

    Darroudi, Firouz [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands)]. E-mail: F.Darroudi@LUMC.NL; Wiegant, Wouter [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands); Meijers, Matty [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands); Friedl, Anna A. [Radiobiological Institute, University of Munich, Munich (Germany); Institute of Radiobiology, GSF National Research Center for Environment and Health, Neuherberg (Germany); Burg, Mirjam van der [Department of Immunology, Erasmus Medical Centre, Rotterdam (Netherlands); Fomina, Janna [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands); Dongen, Jacques J.M. van [Department of Immunology, Erasmus Medical Centre, Rotterdam (Netherlands); Gent, Dik C. van [Department of Cell Biology and Genetics, Erasmus Medical Centre, Rotterdam (Netherlands); Zdzienicka, Malgorzata Z. [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands); Department of Molecular Cell Genetics, Collegium Medicum, N. Corpernicus University, Bydgoszcz (Poland)

    2007-02-03

    We analyzed the phenotype of cells derived from SCID patients with different mutations in the Artemis gene. Using clonogenic survival assay an increased sensitivity was found to X-rays (2-3-fold) and bleomycin (2-fold), as well as to etoposide, camptothecin and methylmethane sulphonate (up to 1.5-fold). In contrast, we did not find increased sensitivity to cross-linking agents mitomycin C and cis-platinum. The kinetics of DSB repair assessed by pulsed-field gel electrophoresis and {gamma}H2AX foci formation after ionizing irradiation, indicate that 15-20% of DSB are not repaired in Artemis-deficient cells. In order to get a better understanding of the repair defect in Artemis-deficient cells, we studied chromosomal damage at different stages of the cell cycle. In contrast to AT cells, Artemis-deficient cells appear to have a normal G{sub 1}/S-block that resulted in a similar frequency of dicentrics and translocations, however, frequency of acentrics fragments was found to be 2-4-fold higher compared to normal fibroblasts. Irradiation in G{sub 2} resulted in a higher frequency of chromatid-type aberrations (1.5-3-fold) than in normal cells, indicating that a fraction of DSB requires Artemis for proper repair. Our data are consistent with a function of Artemis protein in processing of a subset of complex DSB, without G{sub 1} cell cycle checkpoint defects. This type of DSB can be induced in high proportion and persist through S-phase and in part might be responsible for the formation of chromatid-type exchanges in G{sub 1}-irradiated Artemis-deficient cells. Among different human radiosensitive fibroblasts studied for endogenous (in untreated samples) as well as X-ray-induced DNA damage, the ranking order on the basis of higher incidence of spontaneously occurring chromosomal alterations and induced ones was: ligase 4 {>=} AT > Artemis. This observation implicates that in human fibroblasts following exposure to ionizing radiation a lower risk might be created when

  1. Role of Artemis in DSB repair and guarding chromosomal stability following exposure to ionizing radiation at different stages of cell cycle.

    Science.gov (United States)

    Darroudi, Firouz; Wiegant, Wouter; Meijers, Matty; Friedl, Anna A; van der Burg, Mirjam; Fomina, Janna; van Dongen, Jacques J M; van Gent, Dik C; Zdzienicka, Małgorzata Z

    2007-02-03

    We analyzed the phenotype of cells derived from SCID patients with different mutations in the Artemis gene. Using clonogenic survival assay an increased sensitivity was found to X-rays (2-3-fold) and bleomycin (2-fold), as well as to etoposide, camptothecin and methylmethane sulphonate (up to 1.5-fold). In contrast, we did not find increased sensitivity to cross-linking agents mitomycin C and cis-platinum. The kinetics of DSB repair assessed by pulsed-field gel electrophoresis and gammaH2AX foci formation after ionizing irradiation, indicate that 15-20% of DSB are not repaired in Artemis-deficient cells. In order to get a better understanding of the repair defect in Artemis-deficient cells, we studied chromosomal damage at different stages of the cell cycle. In contrast to AT cells, Artemis-deficient cells appear to have a normal G(1)/S-block that resulted in a similar frequency of dicentrics and translocations, however, frequency of acentrics fragments was found to be 2-4-fold higher compared to normal fibroblasts. Irradiation in G(2) resulted in a higher frequency of chromatid-type aberrations (1.5-3-fold) than in normal cells, indicating that a fraction of DSB requires Artemis for proper repair. Our data are consistent with a function of Artemis protein in processing of a subset of complex DSB, without G(1) cell cycle checkpoint defects. This type of DSB can be induced in high proportion and persist through S-phase and in part might be responsible for the formation of chromatid-type exchanges in G(1)-irradiated Artemis-deficient cells. Among different human radiosensitive fibroblasts studied for endogenous (in untreated samples) as well as X-ray-induced DNA damage, the ranking order on the basis of higher incidence of spontaneously occurring chromosomal alterations and induced ones was: ligase 4> or =AT>Artemis. This observation implicates that in human fibroblasts following exposure to ionizing radiation a lower risk might be created when cells are devoid of

  2. Detection and isolation of Listeria monocytogenes from food samples: implications of sublethal injury.

    Science.gov (United States)

    Donnelly, Catherine W

    2002-01-01

    Detection of L. monocytogenes is often limited by the performance of the enrichment media used to support bacterial growth to detectable levels. Because Listeria may exist at extremely low levels in foods, sample enrichment protocols must amplify these low initial populations to detectable limits. Listeria may also exist in an injured state in food products as a result of processing treatments such as heating, freezing, exposure to acids, or exposure to sanitizing compounds. Selective agents in enrichment media normally used for recovery of Listeria may inhibit repair and detection of sublethally injured Listeria, which may go on to repair, grow, and regain pathogenicity. Simple modifications to existing regulatory protocols, such as those that use more than one enrichment broth, raise sensitivity of detection to 90%. This review shows the efficacy of repair/enrichment strategies, which increase sensitivity of detection to 97.5-98.8% compared with 65-70% by standard regulatory protocols. Ribotype analysis of isolates obtained from meat samples reveals a complex microbial ecology, with striking differences in both number and distribution of distinct genetic types of Listeria, depending upon whether samples are enriched in selective or repair/enrichment media. In studies on enrichment of dairy environmental samples in University of Vermont medium and Listeria repair broth (UVM and LRB), combining these 2 primary enrichment media into a single tube of Fraser broth for dual secondary enrichment yielded a significantly higher percentage (p samples than did use of either LRB or UVM alone. Refinement of conventional Listeria recovery methods should consider the importance of the enrichment step, the nutritional needs of specific genetic types, and the physiological condition of Listeria isolates in foods.

  3. DNA mismatch repair protein MSH2 dictates cellular survival in response to low dose radiation in endometrial carcinoma cells.

    LENUS (Irish Health Repository)

    Martin, Lynn M

    2013-07-10

    DNA repair and G2-phase cell cycle checkpoint responses are involved in the manifestation of hyper-radiosensitivity (HRS). The low-dose radioresponse of MSH2 isogenic endometrial carcinoma cell lines was examined. Defects in cell cycle checkpoint activation and the DNA damage response in irradiated cells (0.2 Gy) were evaluated. HRS was expressed solely in MSH2+ cells and was associated with efficient activation of the early G2-phase cell cycle checkpoint. Maintenance of the arrest was associated with persistent MRE11, γH2AX, RAD51 foci at 2 h after irradiation. Persistent MRE11 and RAD51 foci were also evident 24 h after 0.2 Gy. MSH2 significantly enhances cell radiosensitivity to low dose IR.

  4. Genetic polymorphisms in XRCC1, OGG1, APE1 and XRCC3 DNA repair genes, ionizing radiation exposure and chromosomal DNA damage in interventional cardiologists

    Energy Technology Data Exchange (ETDEWEB)

    Andreassi, Maria Grazia, E-mail: andreas@ifc.cnr.it [CNR Institute of Clinical Physiology, National Research Council, Pisa (Italy); Foffa, Ilenia [CNR Institute of Clinical Physiology, National Research Council, Pisa (Italy); Sant' Anna School of Advanced Studies, Pisa (Italy); Manfredi, Samantha; Botto, Nicoletta [CNR Institute of Clinical Physiology, National Research Council, Pisa (Italy); Cioppa, Angelo [Clinica Cardiologica ' Montevergine' , Mercogliano (Italy); Picano, Eugenio [CNR Institute of Clinical Physiology, National Research Council, Pisa (Italy); Clinica Cardiologica ' Montevergine' , Mercogliano (Italy)

    2009-06-18

    Interventional cardiologists working in high-volume cardiac catheterization laboratory are exposed to significant occupational radiation risks. Common single-nucleotide polymorphisms (SNPs) in DNA repair genes are thought to modify the effects of low-dose radiation exposure on DNA damage, the main initiating event in the development of cancer and hereditary disease. The aim of this study was to determine the relationship between XRCC1 (Arg194Trp and Arg399Gln), OGG1 (Ser326Cys), APE1 (Asp148Glu) and XRCC3 (Thr241Met) SNPs and chromosomal DNA damage. We enrolled 77 subjects: 40 interventional cardiologists (27 male, 41.3 {+-} 9.4 years and 13 female, 37.8 {+-} 8.4 years) and 37 clinical cardiologists (26 male, 39.4 {+-} 9.5 years and 11 female, 35.0 {+-} 9.8 years) without radiation exposure as the control group. Micronucleus (MN) assay was performed as biomarker of chromosomal DNA damage and an early predictor of cancer. MN frequency was significantly higher in interventional cardiologists than in clinical physicians (19.7 {+-} 7.8 per mille vs. 13.5 {+-} 6.3 per mille , p = 0.0003). Within the exposed group, individuals carrying a XRCC3 Met241 allele had higher frequency than homozygous XRCC3 Thr241 (21.2 {+-} 7.8 per mille vs. 16.6 {+-} 7.1 per mille , p = 0.03). Individuals with two or more risk alleles showed a higher MN frequency when compared to subjects with one or no risk allele (18.4 {+-} 6.6 per mille vs. 14.4 {+-} 6.1 per mille , p = 0.02). An interactive effect was found between smoking, exposure >10 years and the presence of the two or more risk alleles on the MN frequency (F = 6.3, p = 0.02). XRCC3 241Met alleles, particularly in combination with multiple risk alleles of DNA repair genes, contribute to chromosomal DNA damage levels in interventional cardiologists.

  5. ZRBA1, a Mixed EGFR/DNA Targeting Molecule, Potentiates Radiation Response Through Delayed DNA Damage Repair Process in a Triple Negative Breast Cancer Model

    Energy Technology Data Exchange (ETDEWEB)

    Heravi, Mitra [Department of Human Genetics, McGill University, Montreal (Canada); Department of Radiation Oncology, McGill University, Montreal (Canada); Segal Cancer Center, Jewish General Hospital, Montreal (Canada); Kumala, Slawomir [Department of Radiation Oncology, McGill University, Montreal (Canada); Segal Cancer Center, Jewish General Hospital, Montreal (Canada); Rachid, Zakaria; Jean-Claude, Bertrand J. [Cancer Drug Research Laboratory, McGill University Health Center, Montreal (Canada); Radzioch, Danuta [Department of Human Genetics, McGill University, Montreal (Canada); Muanza, Thierry M., E-mail: tmuanza@yahoo.com [Department of Radiation Oncology, McGill University, Montreal (Canada); Segal Cancer Center, Jewish General Hospital, Montreal (Canada)

    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, Western 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.

  6. Modeling and time-dependent dynamics of processes of stimulated depolymerization, auto-repairing, degradation and radiation curing of DNA macromolecules and biopolymers at separated and combined actions of ionizing irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Vysotskii, Vladimir I. E-mail: viv@vhome.kiev.ua; Pinchuk, Anatoliy O.; Kornilova, Alla A.; Samoylenko, Igor I

    2001-12-01

    The time-dependent dynamics of the formation, relaxation and auto-repairing of double breaks of DNA macromolecules at the combined radiation action and non-radiation processes of degradation (e.g. by free radicals) were considered. The auto-repairing of DNA double breaks is connected with the peculiarities of long-range interaction of nucleotide charges, atoms and molecules in the intracellular milieu. The properties of intracellular liquid and the characteristics of force interaction between the end-pairs of nucleotides in the area of DNA break in response to radiation are changed. Each kind of radiation is characterized by a certain effectiveness of the double DNA break formation but simultaneously one creates the conditions for their liquidation. On the basis of the analysis and correlation of these processes the time-dependent theory for DNA degradation was created, including hormesis phenomenon, radiation antagonism, the validity of anomaly influence of low and large doses at sharp and chronic radiation and other effects. The qualitative and quantitative correspondences of the theory and experimental results of radiation biology were obtained.

  7. Potential for heavy particle radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Raju, M.R.; Phillips, T.L.

    1977-03-01

    Radiation therapy remains one of the major forms of cancer treatment. When x rays are used in radiotherapy, there are large variations in radiation sensitivity among tumors because of the possible differences in the presence of hypoxic but viable tumor cells, differences in reoxygenation during treatment, differences in distribution of the tumor cells in their cell cycle, and differences in repair of sublethal damage. When high-LET particles are used, depending upon the LET distribution, these differences are reduced considerably. Because of these differences between x rays and high-LET particle effects, the high-LET particles may be more effective on tumor cells for a given effect on normal cells. Heavy particles have potential application in improving radiotherapy because of improved dose localization and possible advantages of high-LET particles due to their radiobiological characteristics. Protons, because of their defined range, Bragg peak, and small effects of scattering, have good dose localization characteristics. The use of protons in radiotherapy minimizes the morbidity of radiotherapy treatment and is very effective in treating deep tumors located near vital structures. Fast neutrons have no physical advantages over /sup 60/Co gamma rays but, because of their high-LET component, could be very effective in treating tumors that are resistant to conventional radiations. Negative pions and heavy ions combine some of the advantages of protons and fast neutrons.

  8. Potential for heavy particle radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Raju, M.R.; Phillips, T.L.

    1977-03-01

    Radiation therapy remains one of the major forms of cancer treatment. When x rays are used in radiotherapy, there are large variations in radiation sensitivity among tumors because of the possible differences in the presence of hypoxic but viable tumor cells, differences in reoxygenation during treatment, differences in distribution of the tumor cells in their cell cycle, and differences in repair of sublethal damage. When high-LET particles are used, depending upon the LET distribution, these differences are reduced considerably. Because of these differences between x rays and high-LET particle effects, the high-LET particles may be more effective on tumor cells for a given effect on normal cells. Heavy particles have potential application in improving radiotherapy because of improved dose localization and possible advantages of high-LET particles due to their radiobiological characteristics. Protons, because of their defined range, Bragg peak, and small effects of scattering, have good dose localization characteristics. The use of protons in radiotherapy minimizes the morbidity of radiotherapy treatment and is very effective in treating deep tumors located near vital structures. Fast neutrons have no physical advantages over /sup 60/Co gamma rays but, because of their high-LET component, could be very effective in treating tumors that are resistant to conventional radiations. Negative pions and heavy ions combine some of the advantages of protons and fast neutrons.

  9. Diverse Responses to UV-B Radiation and Repair Mechanisms of Bacteria Isolated from High-Altitude Aquatic Environments▿

    Science.gov (United States)

    Fernández Zenoff, V.; Siñeriz, F.; Farías, M. E.

    2006-01-01

    Acinetobacter johnsonii A2 isolated from the natural community of Laguna Azul (Andean Mountains at 4,560 m above sea level), Serratia marcescens MF42, Pseudomonas sp. strain MF8 isolated from the planktonic community, and Cytophaga sp. strain MF7 isolated from the benthic community from Laguna Pozuelos (Andean Puna at 3,600 m above sea level) were subjected to UV-B (3,931 J m−2) irradiation. In addition, a marine Pseudomonas putida strain, 2IDINH, and a second Acinetobacter johnsonii strain, ATCC 17909, were used as external controls. Resistance to UV-B and kinetic rates of light-dependent (UV-A [315 to 400 nm] and cool white light [400 to 700 nm]) and -independent reactivation following exposure were determined by measuring the survival (expressed as CFU) and accumulation of cyclobutane pyrimidine dimers (CPD). Significant differences in survival after UV-B irradiation were observed: Acinetobacter johnsonii A2, 48%; Acinetobacter johnsonii ATCC 17909, 20%; Pseudomonas sp. strain MF8, 40%; marine Pseudomonas putida strain 2IDINH, 12%; Cytophaga sp. strain MF7, 20%; and Serratia marcescens, 21%. Most bacteria exhibited little DNA damage (between 40 and 80 CPD/Mb), except for the benthic isolate Cytophaga sp. strain MF7 (400 CPD/Mb) and Acinetobacter johnsonii ATCC 17909 (160 CPD/Mb). The recovery strategies through dark and light repair were different in all strains. The most efficient in recovering were both Acinetobacter johnsonii A2 and Cytophaga sp. strain MF7; Serratia marcescens MF42 showed intermediate recovery, and in both Pseudomonas strains, recovery was essentially zero. The UV-B responses and recovery abilities of the different bacteria were consistent with the irradiation levels in their native environment. PMID:17056692

  10. Mouse model of sublethal and lethal intraperitoneal glanders (Burkholderia mallei).

    Science.gov (United States)

    Fritz, D L; Vogel, P; Brown, D R; Deshazer, D; Waag, D M

    2000-11-01

    Sixty male BALB/c mice were inoculated intraperitoneally with either a sublethal or a lethal dose of Burkholderia mallei China 7 strain, then killed at multiple time points postinoculation. Histopathologic changes were qualitatively similar in both groups and consisted of pyogranulomatous inflammation. In sublethal study mice, changes were first seen at 6 hours in mediastinal lymph nodes, then in spleen, liver, peripheral lymph nodes, and bone marrow at day 3. These changes generally reached maximal incidence and severity by day 4 but decreased by comparison in all tissues except the liver. Changes were first seen in lethal study mice also at 6 hours in mediastinal lymph nodes and in spleens. At day 1, changes were present in liver, peripheral lymph nodes, and bone marrow. The incidence and severity of these changes were maximal at day 2. In contrast to sublethal study mice, the incidence and severity of the changes did not decrease through the remainder of the study. The most significant difference between the two groups was the rapid involvement of the spleen in the lethal study mice. Changes indicative of impaired vascular perfusion were more frequently seen in the sublethal study mice. Our findings indicate that mice are susceptible to B. mallei infection and may serve as an appropriate model for glanders infection in a resistant host such as human beings. Additionally, by immunoelectron microscopy, we showed the presence of type I O-antigenic polysaccharide (capsular) antigen surrounding B. mallei.

  11. Tendon repair

    Science.gov (United States)

    Repair of tendon ... Tendon repair can be performed using: Local anesthesia (the immediate area of the surgery is pain-free) ... a cut on the skin over the injured tendon. The damaged or torn ends of the tendon ...

  12. The 53BP1 homolog in C. elegans influences DNA repair and promotes apoptosis in response to ionizing radiation.

    Directory of Open Access Journals (Sweden)

    Jin-Sun Ryu

    Full Text Available 53BP1 contributes to activation of the G2/M checkpoint downstream of ATM and MDC1 in response to ionizing radiation and promotes nonhomologous end-joining (NHEJ in mammalian cells. In order to determine whether the cellular activities of 53BP1 are conserved in the model organism C. elegans, we analyzed the function of its homolog, HSR-9 in response to DNA damage. Deletion or Mos1-insertion in hsr-9 did not affect the sensitivity of worms to double strand DNA breaks (DSBs, as reflected in embryonic survival and larval development. Nevertheless, the hsr-9 mutations, as well as a lig-4 deletion, reversed the hypersensitivity of rad-54-deficient worms to DSBs. In addition, oocyte chromosomal aberrations, which were increased by rad-54 knockdown in response to DSBs, were also reduced by the hsr-9 mutations. The hsr-9 mutations did not prevent the cell cycle arrest induced by DSBs in mitotically proliferating germ cells. However, they attenuated apoptosis induced by DSBs, but not when CEP-1 (a p53 ortholog was absent, suggesting that HSR-9 functions in the same pathway as CEP-1. We concluded that the 53BP1 homolog in C. elegans is not directly involved in cell cycle arrest in response to DSBs, but that it promotes apoptosis and also a form of NHEJ that occurs only when rad-54 is deficient.

  13. Oxygen-independent inactivation of Haemophilus influenzae transforming DNA by monochromatic radiation: action spectrum, effect of histidine and repair

    Energy Technology Data Exchange (ETDEWEB)

    Cabrera-Juarez, E.; Setlow, J.K.; Swenson, P.A.; Peak, M.J.

    1976-01-01

    The action spectrum for the oxygen-independent inactivation of native transforming DNA from Haemophilus influenzae with near-uv radiation revealed a shoulder beginning at 334 and extending to 460 nm. The presence of 0.2 M histidine during irradiation produced a small increase in inactivation at 254, 290 and 313 nm, a large increase at 334 nm and a decrease in inactivation at 365, 405, and 460 nm. Photoreactivation did not reverse the DNA damage produced at pH 7.0 at 334, 365, 405 and 460 nm, but did reactivate the DNA after irradiation at 254, 290 and 313 nm. The inactivation of DNA irradiated at 254, 290 and 313 nm was considerably greater when the transforming ability was assayed in an excision-defective mutant compared with the wild type, although DNA irradiated at 334, 365, 405 and 460 nm showed smaller differences. These results suggest that the oxygen-independent inactivation of H. influenzae DNA at pH 7 by irradiation at 334, 365, 405 and 460 nm is caused by lesions other than pyrimidine dimers.

  14. Participation of gap junction communication in potentially lethal damage repair and DNA damage in human fibroblasts exposed to low- or high-LET radiation

    Science.gov (United States)

    Autsavapromporn, Narongchai; Suzuki, Masao; Plante, Ianik; Liu, Cuihua; Uchihori, Yukio; Hei, Tom K.; Azzam, Edouard I.; Murakami, Takeshi

    2014-01-01

    Existing research has not fully explained how different types of ionizing radiation (IR) modulate the responses of cell populations or tissues. In our previous work, we showed that gap junction intercellular communication (GJIC) mediates the propagation of stressful effects among irradiated cells exposed to high linear energy transfer (LET) radiations, in which almost every cells is traversed by an IR track. In the present study, we conducted an in-depth study of the role of GJIC in modulating the repair of potentially lethal damage (PLDR) and micronuclei formation in cells exposed to low- or high-LET IR. Confluent human fibroblasts were exposed in the presence or absence of a gap junction inhibitor to 200 kV X rays (LET ∼ 1.7 keV/µm), carbon ions (LET ∼ 76 keV/µm), silicon ions (LET ∼ 113 keV/µm) or iron ions (LET ∼ 400 keV/µm) that resulted in isosurvival levels. The fibroblasts were incubated for various times at 37 °C. As expected, high-LET IR were more effective than were low-LET X rays at killing cells and damaging DNA shortly after irradiation. However, when cells were held in a confluent state for several hours, PLDR associated with a reduction in DNA damage, occurred only in cells exposed to X rays. Interestingly, inhibition of GJIC eliminated the enhancement of toxic effects, which resulted in an increase of cell survival and reduction in the level of micronucleus formation in cells exposed to high, but not in those exposed to low-LET IR. The experiment shows that gap-junction communication plays an important role in the propagation of stressful effects among irradiated cells exposed to high-LET IR while GJIC has only a minimal effect on PLDR and DNA damage following low-LET irradiation. Together, our results show that PLDR and induction of DNA damage clearly depend on gap-junction communication and radiation quality. PMID:23867854

  15. Sub-lethal irradiation of human colorectal tumor cells imparts enhanced and sustained susceptibility to multiple death receptor signaling pathways.

    Directory of Open Access Journals (Sweden)

    Victoria Ifeadi

    Full Text Available BACKGROUND: Death receptors (DR of the TNF family function as anti-tumor immune effector molecules. Tumor cells, however, often exhibit DR-signaling resistance. Previous studies indicate that radiation can modify gene expression within tumor cells and increase tumor cell sensitivity to immune attack. The aim of this study is to investigate the synergistic effect of sub-lethal doses of ionizing radiation in sensitizing colorectal carcinoma cells to death receptor-mediated apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: The ability of radiation to modulate the expression of multiple death receptors (Fas/CD95, TRAILR1/DR4, TRAILR2/DR5, TNF-R1 and LTβR was examined in colorectal tumor cells. The functional significance of sub-lethal doses of radiation in enhancing tumor cell susceptibility to DR-induced apoptosis was determined by in vitro functional sensitivity assays. The longevity of these changes and the underlying molecular mechanism of irradiation in sensitizing diverse colorectal carcinoma cells to death receptor-mediated apoptosis were also examined. We found that radiation increased surface expression of Fas, DR4 and DR5 but not LTβR or TNF-R1 in these cells. Increased expression of DRs was observed 2 days post-irradiation and remained elevated 7-days post irradiation. Sub-lethal tumor cell irradiation alone exhibited minimal cell death, but effectively sensitized three of three colorectal carcinoma cells to both TRAIL and Fas-induced apoptosis, but not LTβR-induced death. Furthermore, radiation-enhanced Fas and TRAIL-induced cell death lasted as long as 5-days post-irradiation. Specific analysis of intracellular sensitizers to apoptosis indicated that while radiation did reduce Bcl-X(L and c-FLIP protein expression, this reduction did not correlate with the radiation-enhanced sensitivity to Fas and/or TRAIL mediated apoptosis among the three cell types. CONCLUSIONS/SIGNIFICANCE: Irradiation of tumor cells can overcome Fas and TRAIL

  16. Pesticides and Arthropods: Sublethal Effects and Demographic Toxicology

    Directory of Open Access Journals (Sweden)

    Dejan Marčić

    2007-01-01

    Full Text Available Insecticides and acaricides designed to control primary harmful insects and mites may also variously affect some other arthopods present in an (agroecosystem (e.g. secondary pests, predators, parasitoids, saprophytes, bioindicators, pollinators. Apart from insecticides and acaricides, arthropods may also be affected by the activity of other pesticides (fungicides, herbicides, etc.. Regardless of whether they are deemed desirable or not, the effects that pesticides have on arthopods need to be quantified as closely as possible through appropriate experimental procedures. Data acquired in tests designed to determined LD50/LC50 values are inadequate for evaluation of pesticide effectiveness in the field as pesticidesalso cause various sublethal effects, generally disregarded in such investigations. The sublethal effects of pesticides refer to any altered behaviour and/or physiology of individuals that have survived exposure to pesticides at doses/concentrations that can be lethal(within range causing mortality in an experimental population that exceeds mortality in an untreated population or sublethal (below that range. Pesticides affect locomotion and mobility, stimulate dispersion of arthropods from treated areas, complicate or prevent their navigation, orientation and ability to locate hosts, and cause changes in their feeding, mating and egg-laying patterns. Sublethal pesticide effects on arthropod physiology reflect on the life span, rate of development, fecundity and/or fertility, sex ratio and immunity of surviving individuals. Different parameters are being used in arthropod bioassays to determine sublethal effects (ED50/EC50, LOEC, NOEC, total effect index. Compared to acute toxicity tests, these parameters improve the quality of evaluation and create a more accurate view of the effects of a pesticide. However, such approach covers mainly fecundity/fertility alone, while all other sublethal effects remain unaccounted for. Besides, it

  17. Radiation resistence of microorganisms from radiation sterilization processing environments

    Science.gov (United States)

    Sabovljev, Svetlana A.; Žunić, Zora S.

    The radiation resistance of microorganisms was examined on the samples of dust collected from the radiation sterilization processing environments including assembly, storage, and sterilization plant areas. The isolation of radiation resistant strains was performed by irradiation with screening doses ranging from 10 to 35 kGy and test pieces containing 10 6 to 10 8 CFU in dried serum-broth, representing 100 to 5000 colonies of primary cultures of microorganisms from 7 different sites. In an examination of 16900 colonies of aerobic microorganisms from 3 hygienically controlled production sites and 4 uncontrolled ones, 30 strains of bacteria were isolated. Of those 15 were classified as genus Bacillus, 9 as Micrococcus and 6 as Sarcina. All of the 15 strains of Gram positive sporeforming aerobic rods exhibited an exponential decrease in the surviving fraction as a function of dose, indicating that the inactivation of spores of aerobic rods is a consequence of a single energy deposition into the target. All strains were found to be moderately resistant to radiation with D-6 values (dose required to reduce survival to 6 log cycles) between 18 and 26 kGy. All of the isolated Gram positive cocci showed inactivation curves having a shoulder, indicating that different processes are involved in the inactivation of these cells, e.g. accumulation of sublethal lesions, or final repair capacity of potential lethal lesions. Moderate radiation resistance was observed in 13 strains with D-6 values between 16 to 30 kGy. Two slow-growing, red pigmented strains tentatively classified as genus Micrococcus isolated from uncontrolled sites (human dwellings) were exceptionally resistant with D-6 more than 45 kGy. For hygienically controlled sites, Gram positive spereforming rods composed two thirds of the resistant microflora, while Gram positive cocci comprised one third. For hygienically uncontrolled sites this ratio was reversed. An assumption is made that one isolated strain has grown

  18. Radiation sensitivity of the gastrula-stage embryo: Chromosome aberrations and mutation induction in lacZ transgenic mice: The roles of DNA double-strand break repair systems.

    Science.gov (United States)

    Jacquet, Paul; van Buul, Paul; van Duijn-Goedhart, Annemarie; Reynaud, Karine; Buset, Jasmine; Neefs, Mieke; Michaux, Arlette; Monsieurs, Pieter; de Boer, Peter; Baatout, Sarah

    2015-10-01

    At the gastrula phase of development, just after the onset of implantation, the embryo proper is characterized by extremely rapid cell proliferation. The importance of DNA repair is illustrated by embryonic lethality at this stage after ablation of the genes involved. Insight into mutation induction is called for by the fact that women often do not realize they are pregnant, shortly after implantation, a circumstance which may have important consequences when women are subjected to medical imaging using ionizing radiation. We screened gastrula embryos for DNA synthesis, nuclear morphology, growth, and chromosome aberrations (CA) shortly after irradiation with doses up to 2.5Gy. In order to obtain an insight into the importance of DNA repair for CA induction, we included mutants for the non-homologous end joining (NHEJ) and homologous recombination repair (HRR) pathways, as well as Parp1-/- and p53+/- embryos. With the pUR288 shuttle vector assay, we determined the radiation sensitivity for point mutations and small deletions detected in young adults. We found increased numbers of abnormal nuclei 5h after irradiation; an indication of disturbed development was also observed around this time. Chromosome aberrations 7h after irradiation arose in all genotypes and were mainly of the chromatid type, in agreement with a cell cycle dominated by S-phase. Increased frequencies of CA were found for NHEJ and HR mutants. Gastrula embryos are unusual in that they are low in exchange induction, even after compromised HR. Gastrula embryos were radiation sensitive in the pUR288 shuttle vector assay, giving the highest mutation induction ever reported for this genetic toxicology model. On theoretical grounds, a delayed radiation response must be involved. The compromised developmental profile after doses up to 2.5Gy likely is caused by both apoptosis and later cell death due to large deletions. Our data indicate a distinct radiation-sensitive profile of gastrula embryos, including

  19. Sublethal Heavy Metal Stress Stimulates Innate Immunity in Tomato

    Directory of Open Access Journals (Sweden)

    Nilanjan Chakraborty

    2015-01-01

    Full Text Available Effect of sublethal heavy metal stress as plant biotic elicitor for triggering innate immunity in tomato plant was investigated. Copper in in vivo condition induced accumulation of defense enzymes like peroxidase (PO, polyphenol oxidase (PPO, phenylalanine ammonia-lyase (PAL, and β-1,3 glucanase along with higher accumulation of total phenol, antioxidative enzymes (catalase and ascorbate peroxidase, and total chlorophyll content. Furthermore, the treatment also induced nitric oxide (NO production which was confirmed by realtime visualization of NO burst using a fluorescent probe 4,5-diaminofluorescein diacetate (DAF-2DA and spectrophotometric analysis. The result suggested that the sublethal dose of heavy metal can induce an array of plant defense responses that lead to the improvement of innate immunity in plants.

  20. Sublethal heavy metal stress stimulates innate immunity in tomato.

    Science.gov (United States)

    Chakraborty, Nilanjan; Chandra, Swarnendu; Acharya, Krishnendu

    2015-01-01

    Effect of sublethal heavy metal stress as plant biotic elicitor for triggering innate immunity in tomato plant was investigated. Copper in in vivo condition induced accumulation of defense enzymes like peroxidase (PO), polyphenol oxidase (PPO), phenylalanine ammonia-lyase (PAL), and β-1,3 glucanase along with higher accumulation of total phenol, antioxidative enzymes (catalase and ascorbate peroxidase), and total chlorophyll content. Furthermore, the treatment also induced nitric oxide (NO) production which was confirmed by realtime visualization of NO burst using a fluorescent probe 4,5-diaminofluorescein diacetate (DAF-2DA) and spectrophotometric analysis. The result suggested that the sublethal dose of heavy metal can induce an array of plant defense responses that lead to the improvement of innate immunity in plants.

  1. Pneumocystis Pneumonia Increases the Susceptibility of Mice to Sublethal Hyperoxia

    OpenAIRE

    Beck, James M.; Preston, Angela M.; Wilcoxen, Steven E.; Morris, Susan B.; White, Eric S.; Paine, Robert

    2003-01-01

    Patients with Pneumocystis pneumonia often develop respiratory failure after entry into medical care, and one mechanism for this deterioration may be increased alveolar epithelial cell injury. In vitro, we previously demonstrated that Pneumocystis is not cytotoxic for alveolar epithelial cells. In vivo, however, infection with Pneumocystis could increase susceptibility to injury by stressors that, alone, would be sublethal. We examined transient exposure to hyperoxia as a prototypical stress ...

  2. Bladder exstrophy repair

    Science.gov (United States)

    Bladder birth defect repair; Everted bladder repair; Exposed bladder repair; Repair of bladder exstrophy ... Bladder exstrophy repair involves two surgeries. The first surgery is to repair the bladder and the second one is to attach ...

  3. EGFR相关的DNA修复及放射抗拒机制研究现状%Relativity of EGFR signal as a regulatory mechanism to DNA repair and radiation resistance

    Institute of Scientific and Technical Information of China (English)

    白静; 白晓平; 赵巧艳

    2012-01-01

    目的:总结国外关于表皮生长因子受体(EGFR)通过各种信号通路调节DNA修复导致辐射抗拒相关机制的研究进展.方法:应用PubMed数据库系统,以“表皮生长因子受体、信号通路、DNA损伤修复、放射抗拒”为关键词检索2005-01-2011-12的相关文献,共检索到英文文献198篇.纳入标准:1)EGFR的表达;2)辐射抗拒和DNA损伤修复机制;3)EGFR和辐射诱导的DNA损伤修复;4)EGFR信号通路调控DNA损伤修复导致放射抗拒的可能机制.根据纳入标准,纳入分析22篇文献.结果:EGFR过表达与放化疗抗拒相关.它可以通过联接DNA蛋白激酶催化亚单位(DNA-PKcs)来调节放疗诱导的DNA损伤的修复.EGFR及其对DNA修复能力之间的分子连接可能通过该受体的一个或多个下游信号通路介导.结论:EGFR作为调节DNA损伤修复机制的信号通路与放射抗拒之间存在相关性,靶向于其中激活的信号通路可以为改善放射抗拒提供新的治疗思路.%OBJECTIVE:To sum up the articles related to improvement that epidermal growth factor receptor (EGFR) modulate DNA repair after radiation-induced damage through many signal pathways. METHODS: Epidermal growth factor receptor,signal pathway ,DNA-damage repair and radiation resistance were searched as key words by Pubmed database system from 2005-01 to 2011-12, Altogether 198 English literatures were obtained. Enrolled criteria: 1, EGFR expression; 2. mechanism of DNA repair and radiation resistances 3, EGFR and radiation resistances 4, EGFR signal as a regulatory mechanism to DNA repair and radiation resistance. By extraction according to enrolled criteria, among roughing hundreds of relative articles,46 papers were selected, and 22 papers were finally analyzed. RESULTS: EGFR Overexpres-sion is associated with resistance to chemotherapy and radiotherapy. It modulates DNA repair after radiation-induced damage through association with the catalytic subunit of DNA protein

  4. The effects of altered fractionation schedules on the survival of human cell lines differing in their proliferative activity and repair capacity

    Energy Technology Data Exchange (ETDEWEB)

    Konefal, J.B.; Taylor, Y.C. (Washington Univ. School of Medicine, St. Louis, MO (USA))

    1989-11-01

    Plateau phase cultures of human cell lines were used as model systems to study the relative influences of proliferation and repair on the effectiveness of altered fractionation schedules. A human normal diploid fibroblast cell line (AG1522) which has a high capacity to repair potentially lethal radiation damage (PLD) and very little proliferative activity when grown to confluence was compared to human tumor cell lines which maintain significant cell-cycle activity in plateau phase. The human fibrosarcoma cell line, HT1080, used in the present study exhibited a much greater rate of turnover than the normal fibroblasts as determined from tritiated thymidine incorporation (5 day labeling index of 66% vs 20%) and no PLD repair, as determined by delayed plating experiments, in plateau phase. Twenty Gy were delivered to both cell lines over 5 days in 3 regimens: one 4 Gy fraction/day, two 2 Gy fractions/day with a 2 hr interval between doses, and two 2 Gy fractions/day with a 6 hr interval between doses. Although the normal fibroblasts demonstrated the greatest sparing between acute single doses and one 4 Gy fraction/day, there was little additional benefit (increased survival) from the increased dose fractionation. In contrast, the twice daily fractionation schedules resulted in significant differential sparing of the fibrosarcoma cells compared to the normal fibroblasts. With the 6 hr interval between doses, the survival advantages of the cell line with the slow turnover rate and high PLD repair capacity were completely lost. Split-dose experiments indicated slightly less sublethal damage repair in the fibrosarcoma cell line, but for both cell lines recovery was complete in 2 hr. DNA distributions were measured by flow cytometry and long term labeling index measurements performed in parallel with the multifraction radiation survival studies.

  5. [Studies of the repair of radiation-induced genetic damage in Drosophila]. Annual progress report, February 1, 1993--November 1, 1994

    Energy Technology Data Exchange (ETDEWEB)

    Hawley, R.S.

    1998-09-01

    This research focuses on two repair deficient mutations in Drosophila melanogaster, namely mei-9, mei-41. In addition, the authors propose to extend this study to include the mus-312 mutation. They expect these studies to provide substantial insights into both the molecular mechanisms of DNA repair in Drosophila and the role these genes play in normal biological processes.

  6. [Studies of the repair of radiation-induced genetic damage in Drosophila]. Annual progress report, February 1, 1993--November 1, 1994

    Energy Technology Data Exchange (ETDEWEB)

    Hawley, R.S.

    1998-09-01

    This research focuses on two repair deficient mutations in Drosophila melanogaster, namely mei-9, mei-41. In addition, the authors propose to extend this study to include the mus-312 mutation. They expect these studies to provide substantial insights into both the molecular mechanisms of DNA repair in Drosophila and the role these genes play in normal biological processes.

  7. Targeting base excision repair as a sensitization strategy in radiotherapy.

    NARCIS (Netherlands)

    Vens, C.; Begg, A.C.

    2010-01-01

    Cellular DNA repair determines survival after ionizing radiation. Human tumors commonly exhibit aberrant DNA repair since they drive mutagenesis and chromosomal instability. Recent reports have shown alterations in the base excision repair (BER) and single strand break repair (SSBR) pathways in huma

  8. A Markov decision process approach to temporal modulation of dose fractions in radiation therapy planning.

    Science.gov (United States)

    Kim, M; Ghate, A; Phillips, M H

    2009-07-21

    The current state of the art in cancer treatment by radiation optimizes beam intensity spatially such that tumors receive high dose radiation whereas damage to nearby healthy tissues is minimized. It is common practice to deliver the radiation over several weeks, where the daily dose is a small constant fraction of the total planned. Such a 'fractionation schedule' is based on traditional models of radiobiological response where normal tissue cells possess the ability to repair sublethal damage done by radiation. This capability is significantly less prominent in tumors. Recent advances in quantitative functional imaging and biological markers are providing new opportunities to measure patient response to radiation over the treatment course. This opens the door for designing fractionation schedules that take into account the patient's cumulative response to radiation up to a particular treatment day in determining the fraction on that day. We propose a novel approach that, for the first time, mathematically explores the benefits of such fractionation schemes. This is achieved by building a stylistic Markov decision process (MDP) model, which incorporates some key features of the problem through intuitive choices of state and action spaces, as well as transition probability and reward functions. The structure of optimal policies for this MDP model is explored through several simple numerical examples.

  9. Modeling marrow damage from response data: Morphallaxis from radiation biology to benzene toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Jones, T.D.; Morris, M.D.; Hasan, J.S.

    1995-12-01

    Consensus principles from radiation biology were used to describe a generic set of nonlinear, first-order differential equations for modeling of toxicity-induced compensatory cell kinetics in terms of sublethal injury, repair, direct killing, killing of cells with unrepaired sublethal injury, and repopulation. This cellular model was linked to a probit model of hematopoietic mortality that describes death from infection and/or hemorrhage between {approximately} 5 and 30 days. Mortality data from 27 experiments with 851 doseresponse groups, in which doses were protracted by rate and/or fractionation, were used to simultaneously estimate all rate constants by maximum-likelihood methods. Data used represented 18,940 test animals distributed according to: (mice, 12,827); (rats, 2,925); (sheep, 1,676); (swine, 829); (dogs, 479); and (burros, 204). Although a long-term, repopulating hematopoietic stem cell is ancestral to all lineages needed to restore normal homeostasis, the dose-response data from the protracted irradiations indicate clearly that the particular lineage that is ``critical`` to hematopoietic recovery does not resemble stem-like cells with regard to radiosensitivity and repopulation rates. Instead, the weakest link in the chain of hematopoiesis was found to have an intrinsic radioresistance equal to or greater than stromal cells and to repopulate at the same rates. Model validation has been achieved by predicting the LD{sub 50} and/or fractional group mortality in 38 protracted-dose experiments (rats and mice) that were not used in the fitting of model coefficients.

  10. YNK1, the yeast homolog of human metastasis suppressor NM23, is required for repair of UV radiation- and etoposide-induced DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Yang Mengmeng; Jarrett, Stuart G.; Craven, Rolf [Department of Molecular and Biomedical Pharmacology, College of Medicine, University of Kentucky, Lexington, KY 40536-0298 (United States); Kaetzel, David M. [Department of Molecular and Biomedical Pharmacology, College of Medicine, University of Kentucky, Lexington, KY 40536-0298 (United States)], E-mail: dmkaetz@uky.edu

    2009-01-15

    In humans, NM23-H1 is a metastasis suppressor whose expression is reduced in metastatic melanoma and breast carcinoma cells, and which possesses the ability to inhibit metastatic growth without significant impact on the transformed phenotype. NM23-H1 exhibits three enzymatic activities in vitro, each with potential to maintain genomic stability, a 3'-5' exonuclease and two kinases, nucleoside diphosphate kinase (NDPK), and protein histidine kinase. Herein we have investigated the potential contributions of NM23 proteins to DNA repair in the yeast, Saccharomyces cerevisiae, which contains a single NM23 homolog, YNK1. Ablation of YNK1 delayed repair of UV- and etoposide-induced nuclear DNA damage by 3-6 h. However, YNK1 had no impact upon the kinetics of MMS-induced DNA repair. Furthermore, YNK1 was not required for repair of mitochondrial DNA damage. To determine whether the nuclear DNA repair deficit manifested as an increase in mutation frequency, the CAN1 forward assay was employed. An YNK1 deletion was associated with increased mutation rates following treatment with either UV (2.6x) or MMS (1.6x). Mutation spectral analysis further revealed significantly increased rates of base substitution and frameshift mutations following UV treatment in the ynk1{delta} strain. This study indicates a novel role for YNK1 in DNA repair in yeast, and suggests an anti-mutator function that may contribute to the metastasis suppressor function of NM23-H1 in humans.

  11. Sublethal effect of neem extract on mediterranean fruit fly adults

    Directory of Open Access Journals (Sweden)

    Márcio Alves Silva

    2013-03-01

    Full Text Available The sublethal effect of extracts of Azadirachta indica on Ceratitis capitata was evaluated. Two pairs of flies were treated in plastic tubes with cotton placed in plastic cages. An artificial diet (hydrolyzed protein + sugar was provided ad libitum. The extracts affected significantly the longevity of C. capitata. The pre-oviposition period were not significantly affected by the extracts. The A. indica branches extracted with dichloromethane (888 ppm affected significantly the fecundity and fertility, reducing the number of eggs laid to approximately 80 % and the egg hatching by 30 % at the 8th day. Therefore, the neem branches extracted with dichloromethane affected the reproduction of C. capitata.

  12. Hypospadias repair

    Science.gov (United States)

    ... the problem. If the repair is not done, problems may occur later on such as: Difficulty controlling and directing urine stream A curve in the penis during erection Decreased fertility Embarrassment about appearance of penis Surgery ...

  13. Functional modifications of macrophage activity after sublethal irradiation. [Toxoplasma gondii

    Energy Technology Data Exchange (ETDEWEB)

    Swartz, R.P.

    1982-01-01

    The modifications of macrophage activity following sublethal irradiation, both in vivo and in vitro, were studied using spreading and C3b-receptor-mediated ingestion assays. Nonelicited peritoneal washout cells were examined for changes in activity and selected population characteristics. The cells from irradiated mice were from a resident peritoneal population and not immigrating cells. The macrophage population showed enhanced activity early with a refractory period (24-48) when the macrophages were unresponsive to stimulation by irradiated lymphocytes. The enhanced activity was inversely dose dependent on macrophage. The lymphocytes showed a regulatory function(s) on the time post irradiation at which they were examined. Early lymphocytes exhibited the ability to enhance the activity of normal macrophages while lymphocytes removed 24 hours post irradiation could suppress the activity of already activated macrophages. The effect(s) of the various lymphocyte populations were reproduced with cell-free supernatants which was indicative of the production of lymphokines. Separation on nylon wool columns indicated that the activity resided primarily in the T-cell population of lymphocytes. In vitro irradiation indicated that stimulation of the lymphocytes is macrophage dependent. Additional work indicated that sublethally irradiated macrophages did not inhibit replication of the coccidian protozoon Toxoplasma gondii although they did show increased phagocytosis. Examination of the serum from whole body irradiated mice showed the presence of a postirradiation substance which enhanced the phagocytosis of normal macrophages. It was not present in the serum of normal mice and was not endotoxin.

  14. Toxicokinetic-toxicodynamic modeling of quantal and graded sublethal endpoints: a brief discussion of concepts

    NARCIS (Netherlands)

    Ashauer, R.; Agatz, A.; Albert, C.; Ducrot, V.; Galic, N.G.; Hendriks, J.; Jager, T.; Kretschmann, A.; O'Connor, I.; Rubach, M.N.; Nyman, M.; Schmitt, W.; Stadnicka, J.; Brink, van den P.J.

    2011-01-01

    We report on the advantages and problems of using toxicokinetic-toxicodynamic (TKTD) models for the analysis, understanding, and simulation of sublethal effects. Only a few toxicodynamic approaches for sublethal effects are available. These differ in their effect mechanism and emphasis on linkages b

  15. Sublethal effect of imidacloprid on Solenopsis invicta (Hymenoptera: Formicidae) feeding, digging, and foraging behavior

    Science.gov (United States)

    There is increasing evidence that exposure to neonicotinoid insecticides at sublethal levels impairs colonies of honeybee and other pollinators. Recently, it was found that sublethal contamination with neonicotinoids also affect growth and behavior of ants. In this study, we exposed red imported fi...

  16. Toxicokinetic-toxicodynamic modeling of quantal and graded sublethal endpoints: a brief discussion of concepts

    NARCIS (Netherlands)

    Ashauer, R.; Agatz, A.; Albert, C.; Ducrot, V.; Galic, N.G.; Hendriks, J.; Jager, T.; Kretschmann, A.; O'Connor, I.; Rubach, M.N.; Nyman, M.; Schmitt, W.; Stadnicka, J.; Brink, van den P.J.

    2011-01-01

    We report on the advantages and problems of using toxicokinetic-toxicodynamic (TKTD) models for the analysis, understanding, and simulation of sublethal effects. Only a few toxicodynamic approaches for sublethal effects are available. These differ in their effect mechanism and emphasis on linkages

  17. Survival rate of honeybee (Apis mellifera) workers after exposure to sublethal concentrations of imidacloprid

    NARCIS (Netherlands)

    Blacquiere, T.

    2010-01-01

    Imidacloprid is a commonly used systemic insecticide which can induce several sublethal effects. Previous research has not shown any increased mortality in bees that were fed with sublethal doses. However, there is very little research conducted with the focus on survival rate of honeybees in the fi

  18. The type and yield of ionising radiation induced chromosomal aberrations depend on the efficiency of different DSB repair pathways in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Natarajan, Adayapalam T.; Berni, Andrea; Marimuthu, Kodumudi M. [Department of Agrobiology and Agrochemistry, University of Tuscia, Via San Camillo de Lellis, 01100 Viterbo (Italy); Palitti, Fabrizio [Department of Agrobiology and Agrochemistry, University of Tuscia, Via San Camillo de Lellis, 01100 Viterbo (Italy)], E-mail: palitti@unitus.it

    2008-07-03

    In order to evaluate the relative role of two major DNA double strand break repair pathways, i.e., non-homologous end joining (NHEJ) and homologous recombination repair (HRR), CHO mutants deficient in these two pathways and the parental cells (AA8) were X-irradiated with various doses. The cells were harvested at different times after irradiation, representing G{sub 2}, S and G{sub 1} phase at the time of irradiation, The mutant cell lines used were V33 (NHEJ deficient), Irs1SF, 51-D1 (HRR deficient). In addition to parental cell line (AA8), a revertant of V33, namely V33-155 was employed. Both types of mutant cells responded with increased frequencies of chromosomal aberrations at all recovery times in comparison to the parental and revertant cells. Mutant cells deficient in NHEJ were more sensitive in all cell stages in comparison to HRR deficient mutant cells, indicating NHEJ is the major repair pathway for DSB repair through out the cell cycle. Both chromosome and chromatid types of exchange aberrations were observed following G{sub 1} irradiation (16 and 24 h recovery). Interestingly, configurations involving both chromosome (dicentrics) and chromatid exchanges were encountered in G{sub 1} irradiated V33 cells. This may indicate that unrepaired DSBs accumulate in G{sub 1} in these mutant cells and carried over to S phase, where they are repaired by HRR or other pathways such as B-NHEJ (back up NHEJ), which appear to be highly error prone. Both NHEJ and HRR, which share some of the same proteins in their pathways, are involved in the repair of DSBs leading to chromosomal aberrations, but with a major role of NHEJ in all stages of cell cycle.

  19. Role of ubiquitination in meiotic recombination repair

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Programmed and unprogrammed double-strand breaks (DSBs) often arise from such physiological requirements as meiotic recombination, and exogenous insults, such as ionizing radiation (IR). Due to deleterious impacts on genome stability, DSBs must be appropriately processed and repaired in a regulatory manner. Recent investigations have indicated that ubiquitination is a critical factor in DNA damage response and meiotic recombination repair. This review summarizes the effects of proteins and complexes associated with ubiquitination with regard to homologous recombination (HR)-dependent DSB repair.

  20. Feasibility of measuring radiation-induced DNA double strand breaks and their repair by pulsed field gel electrophoresis in freshly isolated cells from the mouse RIF-1 tumor

    NARCIS (Netherlands)

    vanWaarde, MAWH; vanAssen, AJ; Konings, AWT; Kampinga, HH

    1996-01-01

    Purpose: To examine the technical feasibility of pulsed field gel electrophoresis (PFGE) as a predictive assay for the radioresponsiveness of tumors. Induction and repair of DNA double strand breaks (DSBs) in a freshly prepared cell suspension from a RIF-1 tumor (irradiated ex vivo) was compared

  1. Femoral hernia repair

    Science.gov (United States)

    Femorocele repair; Herniorrhaphy; Hernioplasty - femoral ... During surgery to repair the hernia, the bulging tissue is pushed back in. The weakened area is sewn closed or strengthened. This repair ...

  2. Undescended testicle repair

    Science.gov (United States)

    Orchidopexy; Inguinal orchidopexy; Orchiopexy; Repair of undescended testicle; Cryptorchidism repair ... first year of life without treatment. Undescended testicle repair surgery is recommended for patients whose testicles do ...

  3. Intestinal obstruction repair

    Science.gov (United States)

    Repair of volvulus; Intestinal volvulus - repair; Bowel obstruction - repair ... Intestinal obstruction repair is done while you are under general anesthesia . This means you are asleep and DO NOT feel pain. ...

  4. Aortic aneurysm repair - endovascular

    Science.gov (United States)

    EVAR; Endovascular aneurysm repair - aorta; AAA repair - endovascular; Repair - aortic aneurysm - endovascular ... Endovascular aortic repair is done because your aneurysm is very large, growing quickly, or is leaking or bleeding. You may have ...

  5. Effect of ionizing radiation in sensory ganglion neurons: organization and dynamics of nuclear compartments of DNA damage/repair and their relationship with transcription and cell cycle.

    Science.gov (United States)

    Casafont, Iñigo; Palanca, Ana; Lafarga, Vanesa; Berciano, Maria T; Lafarga, Miguel

    2011-10-01

    Neurons are very sensitive to DNA damage induced by endogenous and exogenous genotoxic agents, as defective DNA repair can lead to neurodevelopmental disorders, brain tumors and neurodegenerative diseases with severe clinical manifestations. Understanding the impact of DNA damage/repair mechanisms on the nuclear organization, particularly on the regulation of transcription and cell cycle, is essential to know the pathophysiology of defective DNA repair syndromes. In this work, we study the nuclear architecture and spatiotemporal organization of chromatin compartments involved in the DNA damage response (DDR) in rat sensory ganglion neurons exposed to X-ray irradiation (IR). We demonstrate that the neuronal DDR involves the formation of two categories of DNA-damage processing chromatin compartments: transient, disappearing within the 1 day post-IR, and persistent, where unrepaired DNA is accumulated. Both compartments concentrate components of the DDR pathway, including γH2AX, pATM and 53BP1. Furthermore, DNA damage does not induce neuronal apoptosis but triggers the G0-G1 cell cycle phase transition, which is mediated by the activation of the ATM-p53 pathway and increased protein levels of p21 and cyclin D1. Moreover, the run on transcription assay reveals a severe inhibition of transcription at 0.5 h post-IR, followed by its rapid recovery over the 1 day post-IR in parallel with the progression of DNA repair. Therefore, the response of healthy neurons to DNA damage involves a transcription- and cell cycle-dependent but apoptosis-independent process. Furthermore, we propose that the segregation of unrepaired DNA in a few persistent chromatin compartments preserves genomic stability of undamaged DNA and the global transcription rate in neurons.

  6. Motorcycle Repair.

    Science.gov (United States)

    Hein, Jim; Bundy, Mike

    This motorcycle repair curriculum guide contains the following ten areas of study: brake systems, clutches, constant mesh transmissions, final drives, suspension, mechanical starting mechanisms, electrical systems, fuel systems, lubrication systems, and overhead camshafts. Each area consists of one or more units of instruction. Each instructional…

  7. 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

    Directory of Open Access Journals (Sweden)

    Pankaj Chaudhary

    2011-01-01

    Full Text Available 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.

  8. Turbine repair process, repaired coating, and repaired turbine component

    Energy Technology Data Exchange (ETDEWEB)

    Das, Rupak; Delvaux, John McConnell; Garcia-Crespo, Andres Jose

    2015-11-03

    A turbine repair process, a repaired coating, and a repaired turbine component are disclosed. The turbine repair process includes providing a turbine component having a higher-pressure region and a lower-pressure region, introducing particles into the higher-pressure region, and at least partially repairing an opening between the higher-pressure region and the lower-pressure region with at least one of the particles to form a repaired turbine component. The repaired coating includes a silicon material, a ceramic matrix composite material, and a repaired region having the silicon material deposited on and surrounded by the ceramic matrix composite material. The repaired turbine component a ceramic matrix composite layer and a repaired region having silicon material deposited on and surrounded by the ceramic matrix composite material.

  9. Integration of principles of systems biology and radiation biology: toward development of in silico models to optimize IUdR-mediated radiosensitization of DNA mismatch repair-deficient (damage tolerant human cancers

    Directory of Open Access Journals (Sweden)

    Timothy James Kinsella

    2011-08-01

    Full Text Available Over the last 7 years, we have focused our experimental and computational research efforts on improving our understanding of the biochemical, molecular, and cellular processing of iododeoxyuridine (IUdR and ionizing radiation (IR induced DNA base damage by DNA mismatch repair (MMR. These coordinated research efforts, sponsored by the National Cancer Institute Integrative Cancer Biology Program (ICBP, brought together system scientists with expertise in engineering, mathematics, and complex systems theory and translational cancer researchers with expertise in radiation biology. Our overall goal was to begin to develop computational models of IUdR- and/or IR- induced base damage processing by MMR that may provide new clinical strategies to optimize IUdR-mediated radiosensitiztion in MMR deficient (MMR- damage tolerant human cancers. Using multiple scales of experimental testing, ranging from purified protein systems to in vitro (cellular and to in vivo (human tumor xenografts in athymic mice models, we have begun to integrate and interpolate these experimental data with hybrid stochastic biochemical models of MMR damage processing and probabilistic cell cycle regulation models through a systems biology approach. In this article, we highlight the results and current status of our integration of radiation biology approaches and computational modeling to enhance IUdR-mediated radiosensitization in MMR- damage tolerant cancers.

  10. 53BP1 is limiting for NHEJ repair in ATM-deficient model systems that are subjected to oncogenic stress or radiation.

    Science.gov (United States)

    Rybanska-Spaeder, Ivana; Reynolds, Taylor L; Chou, Jeremy; Prakash, Mansi; Jefferson, Tameca; Huso, David L; Desiderio, Stephen; Franco, Sonia

    2013-10-01

    The DNA damage response (DDR) factors ataxia telangiectasia mutated (ATM) and p53 binding protein 1 (53BP1) function as tumor suppressors in humans and mice, but the significance of their mutual interaction to the suppression of oncogenic translocations in vivo has not been investigated. To address this question, the phenotypes of compound mutant mice lacking 53BP1 and ATM (Trp53bp1(-/-)/Atm(-/-)), relative to single mutants, were examined. These analyses revealed that loss of 53BP1 markedly decreased the latency of T-lineage lymphomas driven by RAG-dependent oncogenic translocations in Atm(-/-) mice (average survival, 14 and 23 weeks for Trp53bp1(-/-)/Atm(-/-) and Atm(-/-) mice, respectively). Mechanistically, 53BP1 deficiency aggravated the deleterious effect of ATM deficiency on nonhomologous end-joining (NHEJ)-mediated double-strand break repair. Analysis of V(D)J recombinase-mediated coding joints and signal joints in Trp53bp1(-/-)/Atm(-/-) primary thymocytes is, however, consistent with canonical NHEJ-mediated repair. Together, these findings indicate that the greater NHEJ defect in the double mutant mice resulted from decreased efficiency of rejoining rather than switching to an alternative NHEJ-mediated repair mechanism. Complementary analyses of irradiated primary cells indicated that defects in cell-cycle checkpoints subsequently function to amplify the NHEJ defect, resulting in more frequent chromosomal breaks and translocations in double mutant cells throughout the cell cycle. Finally, it was determined that 53BP1 is dispensable for the formation of RAG-mediated hybrid joints in Atm(-/-) thymocytes but is required to suppress large deletions in a subset of hybrid joints. The current study uncovers novel ATM-independent functions for 53BP1 in the suppression of oncogenic translocations and in radioprotection.

  11. Fibroblast growth factor 2 and DNA repair involvement in the keratinocyte stem cells response to ionizing radiation; Implication du FGF2 (fibroblast growth factor 2) et la reparation de l'ADN dans la reponse des keratinocytes souches aux irradiations

    Energy Technology Data Exchange (ETDEWEB)

    Harfouche, L' Emira Ghida

    2010-02-15

    Keratinocyte stem cells (KSCs) from the human inter follicular epidermis are regarded as the major target to radiation during radiotherapy. We found herein that KSCs are more resistant to ionizing radiation than their direct progeny, and presented more rapid DNA damage repair kinetics than the progenitors. Furthermore, we provided evidence describing the effect of fibroblast growth factor 2 (FGF2) signaling on the ability of KSCs and progenitors to repair damaged DNA. Despite our knowledge of the fact, that FGF is an anti-apoptotic factor in multiple cell types, the direct link between DNA repair and FGF2 signaling has rarely been shown. Existence of such link is an important issue with implications not only to stem cell field but also to cancer therapy. (author)

  12. EVALUATION OF SUBLETHAL EFFECTS OF Ipomoea cairica LINN. EXTRACT ON LIFE HISTORY TRAITS OF DENGUE VECTORS

    OpenAIRE

    Zuharah, Wan Fatma; AHBIRAMI, Rattanam; Dieng, Hamady; Thiagaletchumi, Maniam; Nik FADZLY

    2016-01-01

    Plant derived insecticides have considerable potential for mosquito control because these products are safer than conventional insecticides. This study aimed to investigate sublethal activities of Ipomoea carica or railway creeper crude acethonilic extract against life history trait of dengue vectors, Aedes albopictus and Aedes aegypti. The late third instar larvae of Ae. albopictus and Ae. aegypti were exposed to a sublethal dose at LC50 and larvae that survived were further cultured. Overal...

  13. [Studies of the repair of radiation-induced genetic damage in Drosophila]. Annual progress report, June 1, 1992--June 30, 1993

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-09-01

    The most interesting discovery made over the past year derives from sequence analysis of cDNAs from the putative mus308 gene. The theoretical translation product of this gene contains a DNA polymerase domain near the carboxy terminus and DNA/RNA helicase motifs near the amino terminus. There is currently no precedent in the literature for a single polypeptide containing both of these domains. The protein appears to be a novel DNA repair enzyme which should be fruitful ground for future enzymological analysis. The authors have identified two ORFs by sequence analysis of the transforming fragment containing the mei-41 gene and of corresponding cDNAs. ORF 1 includes the P element insertion sites and encodes a peptide of 757 amino acids. ORF 2 starts 900 base pairs downstream of ORF 1 and encodes a peptide of 1,037 amino acids. This putative peptide shows homology to the yeast DNA repair genes, rad50 of S. cerevisiae and rad3 of S. pombe.

  14. Oligodendroglial response to ionizing radiation: Dose and dose-rate response

    Energy Technology Data Exchange (ETDEWEB)

    Levy, R.P.

    1991-12-01

    An in vitro system using neuroglia from neonatal rat brain was developed to examine the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute {gamma}-irradiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DIC 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. A new compartmental cell model for radiation response in vitro of the oligodendrocyte population is proposed and examined in relation to the potential reaction to radiation injury in the brain.

  15. Oligodendroglial response to ionizing radiation: Dose and dose-rate response

    Energy Technology Data Exchange (ETDEWEB)

    Levy, Richard P. [Univ. of California, Berkeley, CA (United States)

    1991-12-01

    An in vitro system using neuroglia from neonatal rat brain was developed to examine the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute γ-irradiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DIC 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. A new compartmental cell model for radiation response in vitro of the oligodendrocyte population is proposed and examined in relation to the potential reaction to radiation injury in the brain.

  16. Sublethal effect of agronomical surfactants on the spider Pardosa agrestis.

    Science.gov (United States)

    Niedobová, Jana; Hula, Vladimír; Michalko, Radek

    2016-06-01

    In addition to their active ingredients, pesticides contain also additives - surfactants. Use of surfactants has been increasing over the past decade, but their effects on non-target organisms, especially natural enemies of pests, have been studied only very rarely. The effect of three common agrochemical surfactants on the foraging behavior of the wolf spider Pardosa agrestis was studied in the laboratory. Differences in short-term, long-term, and overall cumulative predatory activities were investigated. We found that surfactant treatment significantly affected short-term predatory activity but had no effect on long-term predatory activity. The surfactants also significantly influenced the cumulative number of killed prey. We also found the sex-specific increase in cumulative kills after surfactants treatment. This is the first study showing that pesticide additives have a sublethal effect that can weaken the predatory activity of a potential biological control agent. More studies on the effects of surfactants are needed to understand how they affect beneficial organisms in agroecosystems.

  17. Sublethal toxicity of chlorpyrifos to salmonid olfaction after hypersaline acclimation.

    Science.gov (United States)

    Maryoung, Lindley A; Blunt, Brian; Tierney, Keith B; Schlenk, Daniel

    2015-04-01

    Salmonid habitats can be impacted by several environmental factors, such as salinization, which can also affect salmonid tolerance to anthropogenic stressors, such as pesticides. Previous studies have shown that hypersaline acclimation enhances the acute toxicity of certain organophosphate and carbamate pesticides to euryhaline fish; however, sublethal impacts have been far less studied. The current study aims to determine how hypersaline acclimation and exposure to the organophosphate chlorpyrifos (CPF) impact salmonid olfaction. Combined acclimation and exposure to CPF was shown to impact rainbow trout olfaction at the molecular, physiological, and behavioral levels. Concurrent exposure to hypersalinity and 0.5μg/L CPF upregulated four genes (chloride intracellular channel 4, G protein zgc:101761, calcium calmodulin dependent protein kinase II delta, and adrenergic alpha 2C receptor) that inhibit olfactory signal transduction. At the physiological level, hypersalinity and chlorpyrifos caused a decrease in sensory response to the amino acid l-serine and the bile salt taurocholic acid. Combined acclimation and exposure also negatively impacted behavior and reduced the avoidance of a predator cue (l-serine). Thus, acclimation to hypersaline conditions and exposure to environmentally relevant concentrations of chlorpyrifos caused an inhibition of olfactory signal transduction leading to a decreased response to odorants and impairment of olfactory mediated behaviors.

  18. The deinococcal DdrB protein is involved in an early step of DNA double strand break repair and in plasmid transformation through its single-strand annealing activity.

    Science.gov (United States)

    Bouthier de la Tour, Claire; Boisnard, Stéphanie; Norais, Cédric; Toueille, Magali; Bentchikou, Esma; Vannier, Françoise; Cox, Michael M; Sommer, Suzanne; Servant, Pascale

    2011-12-10

    The Deinococcus radiodurans bacterium exhibits an extreme resistance to ionizing radiation. Here, we investigated the in vivo role of DdrB, a radiation-induced Deinococcus specific protein that was previously shown to exhibit some in vitro properties akin to those of SSB protein from Escherichia coli but also to promote annealing of single stranded DNA. First we report that the deletion of the C-terminal motif of the DdrB protein, which is similar to the SSB C-terminal motif involved in recruitment to DNA of repair proteins, did neither affect cell radioresistance nor DNA binding properties of purified DdrB protein. We show that, in spite of their different quaternary structure, DdrB and SSB occlude the same amount of ssDNA in vitro. We also show that DdrB is recruited early and transiently after irradiation into the nucleoid to form discrete foci. Absence of DdrB increased the lag phase of the extended synthesis-dependent strand annealing (ESDSA) process, affecting neither the rate of DNA synthesis nor the efficiency of fragment reassembly, as indicated by monitoring DNA synthesis and genome reconstitution in cells exposed to a sub-lethal ionizing radiation dose. Moreover, cells devoid of DdrB were affected in the establishment of plasmid DNA during natural transformation, a process that requires pairing of internalized plasmid single stranded DNA fragments, whereas they were proficient in transformation by a chromosomal DNA marker that integrates into the host chromosome through homologous recombination. Our data are consistent with a model in which DdrB participates in an early step of DNA double strand break repair in cells exposed to very high radiation doses. DdrB might facilitate the accurate assembly of the myriad of small fragments generated by extreme radiation exposure through a single strand annealing (SSA) process to generate suitable substrates for subsequent ESDSA-promoted genome reconstitution.

  19. Energy and Technology Review: Unlocking the mysteries of DNA repair

    Energy Technology Data Exchange (ETDEWEB)

    Quirk, W.A.

    1993-04-01

    DNA, the genetic blueprint, has the remarkable property of encoding its own repair following diverse types of structural damage induced by external agents or normal metabolism. We are studying the interplay of DNA damaging agents, repair genes, and their protein products to decipher the complex biochemical pathways that mediate such repair. Our research focuses on repair processes that correct DNA damage produced by chemical mutagens and radiation, both ionizing and ultraviolet. The most important type of DNA repair in human cells is called excision repair. This multistep process removes damaged or inappropriate pieces of DNA -- often as a string of 29 nucleotides containing the damage -- and replaces them with intact ones. We have isolated, cloned, and mapped several human repair genes associated with the nucleotide excision repair pathway and involved in the repair of DNA damage after exposure to ultraviolet light or mutagens in cooked food. We have shown that a defect in one of these repair genes, ERCC2, is responsible for the repair deficiency in one of the groups of patients with the recessive genetic disorder xeroderma pigmentosum (XP group D). We are exploring ways to purify sufficient quantities (milligrams) of the protein products of these and other repair genes so that we can understand their functions. Our long-term goals are to link defective repair proteins to human DNA repair disorders that predispose to cancer, and to produce DNA-repair-deficient mice that can serve as models for the human disorders.

  20. Combining Heavy Ion Radiation and Artificial MicroRNAs to Target the Homologous Recombination Repair Gene Efficiently Kills Human Tumor Cells

    Energy Technology Data Exchange (ETDEWEB)

    Zheng Zhiming [Department of Neurosurgery, Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan (China); Department of Radiation Oncology, School of Medicine, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Wang Ping; Wang Hongyan; Zhang Xiangming [Department of Radiation Oncology, School of Medicine, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Wang Minli [Division of Life Sciences, Universities Space Research Association, Houston, Texas (United States); Cucinotta, Francis A. [National Aeronautics and Space Administration, Lyndon B. Johnson Space Center, Houston, Texas (United States); Wang Ya, E-mail: ywang94@emory.edu [Department of Radiation Oncology, School of Medicine, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2013-02-01

    Purpose: Previously, we demonstrated that heavy ions kill more cells at the same dose than X-rays because DNA-clustered lesions produced by heavy ions affect nonhomologous end-joining (NHEJ) repair but not homologous recombination repair (HRR). We have also shown that our designed artificial microRNAs (amiRs) could efficiently target XRCC4 (an essential factor for NHEJ) or XRCC2 (an essential factor for HRR) and sensitize human tumor cells to X-rays. Based on these data, we were interested in testing the hypothesis that combining heavy ions and amiRs to target HRR but not NHEJ should more efficiently kill human tumor cells. Methods and Materials: Human tumor cell lines (U87MG, a brain tumor cell line, and A549, a lung cancer cell line) and their counterparts, overexpressed with amiR to target XRCC2, XRCC4 or both, were used in this study. Survival sensitivities were examined using a clonogenic assay after these cells were exposed to X-rays or heavy ions. In addition, these cell lines were subcutaneously injected into nude mice to form xenografts and the tumor size was compared after the tumor areas were exposed to X-rays or heavy ions. Results: Although targeting either XRCC4 (NHEJ factor) or XRCC2 (HRR factor) sensitized the human tumor cells to X-rays, in vitro and the xenograft animal model, targeting only XRCC2 but not XRCC4 sensitized the human tumor cells to heavy ions in vitro and in the xenograft animal model. Conclusions: Combining heavy ions with targeting the HRR pathway, but not the NHEJ pathway, could significantly improve the efficiency of tumor cell death.

  1. The DNA injury-repair of esophageal cancer EC109 cells to diallyl trisulfide (DATS) combining radiation%二烯丙基三硫化物联合辐射对食管癌EC109细胞DNA损伤及修复影响

    Institute of Scientific and Technical Information of China (English)

    Yang Zhang; Hongbing Ma

    2012-01-01

    Objective: The aim of our study was to investigate the effect of diallyl trisulfide (DATS) combining radiation on DNA injury-repair of Esophageal cancer EC109 cells. Methods: Using 10 and 20 μg/mL DATS on EC109 cells, and taking X-ray radiation 24 h later. Investigate the radiosensitization effect of DATS on EC109 cells by clone formation, and the mechanism of DNA injury-repair by Comet Assay. Results: The clone formation resulted that DATS had radiosensitization effect on EC109 cells. Radiosensitization enhancement ratios of 10 and 20 μg/mL DATS in combination with radiation were 1.55,1.64 (Do) and 1.43,1.75 (Dq) respectively. In the comet assay, the TM (tail moments) of 20 μg/mL DATS combining radiation group lines at 0 h, 2 h, 6 h and 24 h were 7.16 ± 2.61,3.65 ± 2.06,2.09 ± 0.83,1.45 ± 1.37 respectively. They were slightly increased than radiation group (0.95 ± 0.65, 0.11 ± 0.07, 0.1 ± 0.05, 0.11 ± 0.08) and DATS group (1.81 ± 1.23,1.58 ± 1.40, 0.45 ± 0.25,0.60 ± 0.40) (P < 0.01). The result showed that DATS combining radiation had the effect of increasing DNA damage and inhibiting DNA repair on EC109 cells. Conclusion: DATS has radiosensitization effect on Esophageal cancer EC109 cells. And the effect is probably related with DNA injury-repair.

  2. Successful excision of a radiation fistula that required a partial sacral resection and repair with a free latissimus dorsi musculocutaneous flap

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Satoshi; Tajima, Sadao; Ueda, Kouichi; Tanaka, Yoshio; Akamatsu, Jun; Ohba, Sohsuke; Ohmiya, Yuka [Osaka Medical Coll., Takatsuki (Japan)

    1996-08-01

    We report a case in which a radiation abscess with its drainage fistula of the presacral region was successfully treated. Eighteen years earlier, the patient, a 76-year-old female, had received radiation therapy after the excision of a uterine cancer. After this surgery, 11 years later, a presacral radiation abscess developed and was treated conservatively for 5 years. As the abscess did not respond, an incision was made for abscess drainage and this method was used for 2 years without success. Construction of a 3D solid model of her pelvis and fistulous tract led to the selection of an effective surgical approach that entailed a partial sacral resection (half of the S3 and the entire S4 and S5 regions), which allowed wide access to the presacral area, so that resecting the abscess was quite easy. On resection, the space was filled with a free latissimus dorsi musculocutaneous flap. The postoperative course has shown no morbidity and continues to remain uneventful. (author)

  3. Eye muscle repair - discharge

    Science.gov (United States)

    ... Lazy eye repair - discharge; Strabismus repair - discharge; Extraocular muscle surgery - discharge ... You or your child had eye muscle repair surgery to correct eye muscle ... term for crossed eyes is strabismus. Children most often ...

  4. Ventral hernia repair

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/007661.htm Ventral hernia repair To use the sharing features on this page, please enable JavaScript. Ventral hernia repair is surgery to repair a ventral hernia. ...

  5. Brain aneurysm repair

    Science.gov (United States)

    ... aneurysm repair; Dissecting aneurysm repair; Endovascular aneurysm repair - brain; Subarachnoid hemorrhage - aneurysm ... Your scalp, skull, and the coverings of the brain are opened. A metal clip is placed at ...

  6. RpoS plays a central role in the SOS induction by sub-lethal aminoglycoside concentrations in Vibrio cholerae.

    Directory of Open Access Journals (Sweden)

    Zeynep Baharoglu

    Full Text Available Bacteria encounter sub-inhibitory concentrations of antibiotics in various niches, where these low doses play a key role for antibiotic resistance selection. However, the physiological effects of these sub-lethal concentrations and their observed connection to the cellular mechanisms generating genetic diversification are still poorly understood. It is known that, unlike for the model bacterium Escherichia coli, sub-minimal inhibitory concentrations (sub-MIC of aminoglycosides (AGs induce the SOS response in Vibrio cholerae. SOS is induced upon DNA damage, and since AGs do not directly target DNA, we addressed two issues in this study: how sub-MIC AGs induce SOS in V. cholerae and why they do not do so in E. coli. We found that when bacteria are grown with tobramycin at a concentration 100-fold below the MIC, intracellular reactive oxygen species strongly increase in V. cholerae but not in E. coli. Using flow cytometry and gfp fusions with the SOS regulated promoter of intIA, we followed AG-dependent SOS induction. Testing the different mutation repair pathways, we found that over-expression of the base excision repair (BER pathway protein MutY relieved this SOS induction in V. cholerae, suggesting a role for oxidized guanine in AG-mediated indirect DNA damage. As a corollary, we established that a BER pathway deficient E. coli strain induces SOS in response to sub-MIC AGs. We finally demonstrate that the RpoS general stress regulator prevents oxidative stress-mediated DNA damage formation in E. coli. We further show that AG-mediated SOS induction is conserved among the distantly related Gram negative pathogens Klebsiella pneumoniae and Photorhabdus luminescens, suggesting that E. coli is more of an exception than a paradigm for the physiological response to antibiotics sub-MIC.

  7. Evaluation of the effect of laser radiation on fibroblast proliferation in repair of skin wounds of rats with iron deficiency anemia

    Science.gov (United States)

    DeCastro, Isabele C. V.; Oliveira-Sampaio, Susana C. P.; Monteiro, Juliana S. de C.; Ferreira, Maria de Fátima L.; Cangussu, Maria T.; N. dos Santos, Jean; Pinheiro, Antonio Luiz B.

    2011-03-01

    The aim of this study was to assess the effect of low- level laser therapy (LLLT) on fibroblast proliferation on wound repair of rats with Iron deficiency anemia since there is no reports on literature about this subject. Iron deficiency anemia was induced on 36 newborn rats then an excisional wound was created on the dorsum of the animals which were divided into four groups: (I) - non-anemic, (II) - Anemic, (III) - non-anemic + LLLT, (IV) Anemic+ LLLT. The animals in each group were sacrificed at 7, 14 and 21 days. Laser irradiation was performed on each group (λ660nm,40Mw,CW) by contact mode with a dose of 2,5J/ cm2 in four points on the area of the wound and total of 10J/cm2 per session. Data were evaluated by analysis of variance (ANOVA) followed by Paired t-test. The results showed LLLT was able to stimulate fibroblastic proliferation in rats with iron deficiency anemia at the 21st day while at control group (III) no statistically significant differences was found.

  8. Databases and Bioinformatics Tools for the Study of DNA Repair

    Directory of Open Access Journals (Sweden)

    Kaja Milanowska

    2011-01-01

    Full Text Available DNA is continuously exposed to many different damaging agents such as environmental chemicals, UV light, ionizing radiation, and reactive cellular metabolites. DNA lesions can result in different phenotypical consequences ranging from a number of diseases, including cancer, to cellular malfunction, cell death, or aging. To counteract the deleterious effects of DNA damage, cells have developed various repair systems, including biochemical pathways responsible for the removal of single-strand lesions such as base excision repair (BER and nucleotide excision repair (NER or specialized polymerases temporarily taking over lesion-arrested DNA polymerases during the S phase in translesion synthesis (TLS. There are also other mechanisms of DNA repair such as homologous recombination repair (HRR, nonhomologous end-joining repair (NHEJ, or DNA damage response system (DDR. This paper reviews bioinformatics resources specialized in disseminating information about DNA repair pathways, proteins involved in repair mechanisms, damaging agents, and DNA lesions.

  9. Sublethal effects of some synthetic and botanical insecticides on Bemisia tabaci (Hemiptera: Aleyrodidae

    Directory of Open Access Journals (Sweden)

    Esmaeily Saeideh

    2014-07-01

    Full Text Available In addition to direct mortality caused by insecticides, some biological traits of insects may also be affected by sublethal insecticide doses. In this study, we used the age-stage, two-sex life table method to evaluate the sublethal effects of the four synthetic insecticides: abamectin, imidacloprid, diazinon, and pymetrozin as well as the botanical insecticide taken from Calotropis procera (Asclepiadaceae extract, on eggs of the cotton whitefly, Bemisia tabaci (Hem.: Aleyrodidae. The lowest and highest survival rates and oviposition periods were observed in whiteflies treated by diazinon and imidacloprid, respectively. We found significant differences in the net reproductive rate (R0, the intrinsic rate of increase (r, the finite rate of increase (?, and the gross reproductive rate (GRR among different insecticides. Altogether, our results showed that pymetrozin and C. procera induced the most sublethal effects, thus they may be suitable candidates for use in integrated pest management programs of B. tabaci.

  10. Effect of novel curcumin-encapsulated chitosan-bioglass drug on bone and skin repair after gamma radiation: experimental study on a Wistar rat model.

    Science.gov (United States)

    Jebahi, S; Saoudi, M; Farhat, L; Oudadesse, H; Rebai, T; Kabir, A; El Feki, A; Keskes, H

    2015-04-01

    Radiation therapy contributes to a significant increase in bone osteoporosis and skin loss. Various natural health products might be beneficial to reduce bone and skin alterations. Curcumin (CUR) medicines derived from natural plants have played an important role in health care. This study aims at synthesizing and evaluating the performance therapy of CUR-encapsulated bioglass-chitosan (CUR-BG-CH). In vitro, the antioxidant assay was evaluated by using 1,1-diphenyl-2-picrylhydrazyl free-radical (DPPH) scavenging and the nitroblue tetrazolium reduction. The CUR-BG-CH antimicrobial effects were tested in liquid media. In vivo, after rat (60) Co γ-radiation, the tissue wound-healing process was studied by grafting CUR and CUR-BG-CH in femoral condyle and dorsal skin rat tissue. The antioxidant studies indicated that CUR-BG-CH quenches free radicals more efficiently than unmodified CUR and had effective DPPH (91%) and superoxide anion (51%) radical scavenging activities. The CUR-BG-CH biomaterial exhibited an important antimicrobial activity against Staphylococcus aureus. The histomorphometric parameters showed amelioration in CUR-BG-CH-treated rats. An improved mechanical property was noticed (33.16 ± 5.0 HV) when compared with that of unmodified CUR group (23.15 ± 4.9 HV). A significant decrease in tumour necrosis factor-α cytokine production was noted in the CUR-BG-CH rats (90 pg/ml) as compared with that of unmodified CUR group (240 pg/ml). The total amount of hydroxyproline was significantly enhanced (33.5%) in CUR-BG-CH group as compared with that of control. Our findings suggested that CUR-BG-CH might have promising potential applications for wound healing.

  11. 11th International Conference of Radiation Research

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-07-18

    Topics discussed in the conference included the following: Radiation Physics, Radiation Chemistry and modelling--Radiation physics and dosimetry; Electron transfer in biological media; Radiation chemistry; Biophysical and biochemical modelling; Mechanisms of DNA damage; Assays of DNA damage; Energy deposition in micro volumes; Photo-effects; Special techniques and technologies; Oxidative damage. Molecular and cellular effects-- Photobiology; Cell cycle effects; DNA damage: Strand breaks; DNA damage: Bases; DNA damage Non-targeted; DNA damage: other; Chromosome aberrations: clonal; Chromosomal aberrations: non-clonal; Interactions: Heat/Radiation/Drugs; Biochemical effects; Protein expression; Gene induction; Co-operative effects; ``Bystander'' effects; Oxidative stress effects; Recovery from radiation damage. DNA damage and repair -- DNA repair genes; DNA repair deficient diseases; DNA repair enzymology; Epigenetic effects on repair; and Ataxia and ATM.

  12. Effect of sublethal preculturing on the survival of probiotics and metabolite formation in set-yoghurt.

    Science.gov (United States)

    Settachaimongkon, Sarn; van Valenberg, Hein J F; Winata, Vera; Wang, Xiaoxi; Nout, M J Robert; van Hooijdonk, Toon C M; Zwietering, Marcel H; Smid, Eddy J

    2015-08-01

    The objective of this study was to investigate the effect of preculturing of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB12 under sublethal stress conditions on their survival and metabolite formation in set-yoghurt. Prior to co-cultivation with yoghurt starters in milk, the two probiotic strains were precultured under sublethal stress conditions (combinations of elevated NaCl and low pH) in a batch fermentor. The activity of sublethally precultured probiotics was evaluated during fermentation and refrigerated storage by monitoring bacterial population dynamics, milk acidification and changes in volatile and non-volatile metabolite profiles of set-yoghurt. The results demonstrated adaptive stress responses of the two probiotic strains resulting in their viability improvement without adverse influence on milk acidification. A complementary metabolomic approach using SPME-GC/MS and (1)H-NMR resulted in the identification of 35 volatiles and 43 non-volatile polar metabolites, respectively. Principal component analysis revealed substantial impact of the activity of sublethally precultured probiotics on metabolite formation demonstrated by distinctive volatile and non-volatile metabolite profiles of set-yoghurt. Changes in relative abundance of various aroma compounds suggest that incorporation of stress-adapted probiotics considerably influences the organoleptic quality of product. This study provides new information on the application of stress-adapted probiotics in an actual food-carrier environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Antifeeding effect of sublethal levels of Cypermethrin and Lamdacyhalothria to rice green leafhopper Nephotettix virescens

    Institute of Scientific and Technical Information of China (English)

    LIUGuangjie; R.M.WILKINS

    1992-01-01

    We evaluated the antifeeding effect of sublethal doses of Cypermethrin and new insecticide Lamdacyhalothrin from the ICI Agrochemicals against rice green leafhopper (GLH). Newly-emerged (0-1 d) females were used in the experiments with five replications for each. Tested females were topically treated with appropriate acetone solutions at 0.2 μl/ female.

  14. The Vf gene for scrab resistance in apple is linked to sub-lethal genes

    NARCIS (Netherlands)

    Gao, Z.S.; Weg, van de W.E.

    2006-01-01

    V f is the most widely used resistance gene in the breeding for scab resistant apple cultivars. Distorted segregation ratios for V f -resistance have frequently been reported. Here we revealed that sub-lethal genes caused the distorted segregation. The inheritance of V f was examined in six progenie

  15. Monitoring colony-level effects of sublethal pesticide exposure on honey bees

    Science.gov (United States)

    The effects of sublethal pesticide exposure to honey bee colonies may be significant but difficult to detect in the field using standard visual assessment methods. Here we describe methods to measure the quantities of adult bees, brood and food resources by weighing hives and hive parts, by photogra...

  16. EVALUATION OF SUBLETHAL EFFECTS OF Ipomoea cairica LINN. EXTRACT ON LIFE HISTORY TRAITS OF DENGUE VECTORS

    Science.gov (United States)

    ZUHARAH, Wan Fatma; AHBIRAMI, Rattanam; DIENG, Hamady; THIAGALETCHUMI, Maniam; FADZLY, Nik

    2016-01-01

    Plant derived insecticides have considerable potential for mosquito control because these products are safer than conventional insecticides. This study aimed to investigate sublethal activities of Ipomoea carica or railway creeper crude acethonilic extract against life history trait of dengue vectors, Aedes albopictus and Aedes aegypti. The late third instar larvae of Ae. albopictus and Ae. aegypti were exposed to a sublethal dose at LC50 and larvae that survived were further cultured. Overall, Ipomea cairica crude extracts affected the whole life history of both Aedes species. The study demonstrated significantly lower egg production (fecundity) and eggs hatchability (fertility) in Ae. albopictus. The sublethal dose of crude extracts reduced significantly the width of larval head capsule and the wing length of both sexes in both Aedes species. The significance of sublethal effects of I. cairica against Aedes mosquitoes was an additional hallmark to demonstrate further activity of this plant despite its direct toxicity to the larvae. The reduced reproductive capacity as well as morphological and physiological anomalies are some of the effects that make I. cairica a potential candidate to be used as a new plant-based insecticide to control dengue vectors. PMID:27253746

  17. Lethal and sublethal effects of cyantraniliprole on Bactrocera dorsalis (Hendle) (Diptera: Tephiritidae)

    Science.gov (United States)

    The oriental fruit fly, Bactrocera dorsalis (Hendel) is one of the most important and damaging fruit pests in the world. Studies were conducted with a novel anthranilic diamide insecticide (i.e. DuPontTM CyazypyrTM) cyantraniliprole to determine its lethal and sublethal effects on B. dorsalis. An in...

  18. Sublethal doses of fipronil intensify synapsin immunostaining in Atta sexdens rubropilosa (Hymenoptera: Formicidae) brains.

    Science.gov (United States)

    Cintra-Socolowski, Priscila; Roat, Thaisa C; Nocelli, Roberta C F; Nunes, Pablo H; Ferreira, Rafael A C; Malaspina, Osmar; Bueno, Odair C

    2016-05-01

    Although ants are common insects in agricultural ecosystems, few studies have considered how xenobiotics might induce physiological and morphological alterations in these insects. This study aimed to verify the neurotoxic action of sublethal doses of fipronil on the mushroom bodies of brains from the leaf-cutting ant Atta sexdens rubropilosa through immunocytochemistry analysis for the protein synapsin. The LD50 value was established as 1.42 ng ant(-1), and the sublethal doses used were LD50/10 and LD50/100. Synapsin labelling was more evident in the brains extracted from ants exposed to the insecticide, specifically in the regions of glia in the mushroom bodies, compared with the control group. It was possible to measure the intensity of emitted fluorescence in the areas of the mushroom bodies, and a statistical test showed differences between the control group and the treatment group. Thus, it is concluded that sublethal doses of the insecticide fipronil intensified synapsin immunostaining, suggesting an increased release of neurotransmitters, which may be linked to neurotoxicity and overexcitation. These sublethal doses may have two different effects: compromising the operation and maintenance of the colony and leading to the establishment of resistance in insects. © 2015 Society of Chemical Industry.

  19. Lethal and sublethal effects of an insect growth regulator, pyriproxyfen, on obliquebanded leafroller (Lepidoptera: Tortricidae).

    Science.gov (United States)

    Sial, Ashfaq A; Brunner, Jay F

    2010-04-01

    The obliquebanded leafroller, Choristoneura rosaceana (Harris) (Lepidoptera: Tortricidae), is one of the most destructive pests of tree fruit in Washington. The development of insecticide resistance in C. rosaceana has led us to explore new management tactics. The use of very low doses of insecticides that have strong sublethal effects represents an environmentally friendly option to improve existing integrated pest management (IPM) strategies. We tested the insect growth regulator pyriproxyfen to determine its lethal and sublethal effects on growth and development of C. rosaceana. A leaf-disk bioassay was used to test seven concentrations of pyriproxyfen ranging from 0 to 30 ppm on fifth-instar C. rosaceana. Male and female larvae were assessed separately for mortality as well as other parameters of growth and development. The LC, values for males and females were 2.4 and 4.8 ppm, respectively. The response to pyriproxyfen was concentration-dependent: only 5-6% of the larvae treated with the highest concentration emerged as morphologically normal adults compared with 86% emergence in the controls. The pupation and adult emergence was significantly delayed at concentrations higher than 1 ppm. The weights of C. rosaceana pupae and adults were significantly increased, whereas fecundity and fertility were significantly reduced at a sublethal concentration of 0.3 ppm. We conclude that both lethal and sublethal effects might exhibit significant impacts on the population dynamics of C. rosaceana in tree fruit orchards treated with low concentrations of pyriproxyfen.

  20. Surface attachment of Listeria monocytogenes is induced by sublethal concentrations of alcohol at low temperatures.

    Science.gov (United States)

    Gravesen, Anne; Lekkas, Charidimos; Knøchel, Susanne

    2005-09-01

    Sublethal concentrations of ethanol or isopropanol increased attachment of Listeria monocytogenes at 10, 20, or 30 degrees C; no induction occurred at 37 degrees C. The alcohol induction phenotype was retained in sigB and cesRK mutants; however, the degree of induction was affected. These results suggest that alcohol may contribute to the persistence of L. monocytogenes.

  1. Sublethal effects of imidacloprid on interactions in a tritrophic system of non-target species.

    Science.gov (United States)

    Uhl, Philipp; Bucher, Roman; Schäfer, Ralf B; Entling, Martin H

    2015-08-01

    Imidacloprid is one of the most used insecticides worldwide, but is highly toxic to non-target arthropods. Effects of sublethal imidacloprid intoxication can potentially propagate in food webs, yet little is known about the impact on non-target populations and communities. We investigated short-term sublethal toxicity of imidacloprid in a tritrophic model system of wild strawberry Fragaria vesca, wood cricket Nemobius sylvestris and nursery web spider Pisaura mirabilis. Strawberries were treated two times with 0mg (control), 1mg (low rate) and 10mg (high rate) of Confidor® WG 70 and crickets were allowed to feed on them. In four lab experiments, we quantified the impact of imidacloprid on leaf damage, growth, behaviour and survival of crickets. The high imidacloprid rate reduced feeding, mass gain, thorax growth and mobility in crickets compared to the control, while mortality was similarly low in all treatments. The low rate reduced mass gain only. Cricket survival of spider predation was higher in the low rate treatment than in the control. Overall, herbivory and predation were reduced at sublethal imidacloprid rates in a non-target organism, three-level food chain, which demonstrates possible propagation of sublethal effects through trophic interactions.

  2. Effect of sublethal preculturing on the survival of probiotics and metabolite formation in set-yoghurt

    NARCIS (Netherlands)

    Settachaimongkon, S.; Valenberg, van H.J.F.; Winata, V.; Wang, X.; Nout, M.J.R.; Hooijdonk, van A.C.M.; Zwietering, M.H.; Smid, E.J.

    2015-01-01

    The objective of this study was to investigate the effect of preculturing of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB12 under sublethal stress conditions on their survival and metabolite formation in set-yoghurt. Prior to co-cultivation with yoghurt starters in milk,

  3. Sublethal effects of hexaflumuron on development and reproduction of the diamondback moth, Plutella xylostella (Lepidoptera: Yponomeutidae)

    Institute of Scientific and Technical Information of China (English)

    Mohammad Mahmoudvand; Habib Abbasipour; Aziz Sheikhi Garian; Ali Reza Bandani

    2011-01-01

    Effects of hexaflumuron at 10% lethal concentration (LC10) and LC25 on development and reproduction parameters of the diamondback moth,Plutella xylostella (Linnaeus,1753) (Lep.:Yponomeutidae) were investigated.Estimated LC50,LC10 and LC25 values of leaf dip bioassay of hexaflumuron on the third instar larvae of the P.xylostella were 1.48,0.59 and 0.91 mg/L,respectively.Hexaflumuron decreased pupal weight in the parent generation at sublethal concentrations but in the offspring generation,this effect was not observed.Sublethal concentrations increased egg,first and second larval instar and pupa developmental time and shortened life span of adults,but did not change the third and fourth larval instars and pre-pupa developmental period.Also fecundity of females reduced significantly but hatchability of treatments and control were similar.Survival rate of pre-adult stages declined significantly at LC25 concentration.Reproduction parameters such as reproductive rate (R0) and intrinsic rate of increase in sublethal concentrations were significantly lower compared with control,but gross reproduction rate (GRR) at the LC10 concentration was increased and it could be hormoligosis.Also hexaflumuron significantly increased doubling time (Dt).We conclude that the sublethal effects of hexaflumuron might exhibit significant effects on the population dynamics of P.xylostella.

  4. EVALUATION OF SUBLETHAL EFFECTS OF Ipomoea cairica LINN. EXTRACT ON LIFE HISTORY TRAITS OF DENGUE VECTORS

    Directory of Open Access Journals (Sweden)

    Wan Fatma ZUHARAH

    2016-01-01

    Full Text Available Plant derived insecticides have considerable potential for mosquito control because these products are safer than conventional insecticides. This study aimed to investigate sublethal activities of Ipomoea carica or railway creeper crude acethonilic extract against life history trait of dengue vectors, Aedes albopictus and Aedes aegypti. The late third instar larvae of Ae. albopictus and Ae. aegypti were exposed to a sublethal dose at LC50 and larvae that survived were further cultured. Overall, Ipomea cairica crude extracts affected the whole life history of both Aedes species. The study demonstrated significantly lower egg production (fecundity and eggs hatchability (fertility in Ae. albopictus. The sublethal dose of crude extracts reduced significantly the width of larval head capsule and the wing length of both sexes in both Aedes species. The significance of sublethal effects of I. cairica against Aedes mosquitoes was an additional hallmark to demonstrate further activity of this plant despite its direct toxicity to the larvae. The reduced reproductive capacity as well as morphological and physiological anomalies are some of the effects that make I. cairica a potential candidate to be used as a new plant-based insecticide to control dengue vectors.

  5. EVALUATION OF SUBLETHAL EFFECTS OF Ipomoea cairica LINN. EXTRACT ON LIFE HISTORY TRAITS OF DENGUE VECTORS.

    Science.gov (United States)

    Zuharah, Wan Fatma; Ahbirami, Rattanam; Dieng, Hamady; Thiagaletchumi, Maniam; Fadzly, Nik

    2016-01-01

    Plant derived insecticides have considerable potential for mosquito control because these products are safer than conventional insecticides. This study aimed to investigate sublethal activities of Ipomoea carica or railway creeper crude acethonilic extract against life history trait of dengue vectors, Aedes albopictus and Aedes aegypti. The late third instar larvae of Ae. albopictus and Ae. aegypti were exposed to a sublethal dose at LC50 and larvae that survived were further cultured. Overall, Ipomea cairica crude extracts affected the whole life history of both Aedes species. The study demonstrated significantly lower egg production (fecundity) and eggs hatchability (fertility) in Ae. albopictus. The sublethal dose of crude extracts reduced significantly the width of larval head capsule and the wing length of both sexes in both Aedes species. The significance of sublethal effects of I. cairica against Aedes mosquitoes was an additional hallmark to demonstrate further activity of this plant despite its direct toxicity to the larvae. The reduced reproductive capacity as well as morphological and physiological anomalies are some of the effects that make I. cairica a potential candidate to be used as a new plant-based insecticide to control dengue vectors.

  6. Physiological stress and ethanol accumulation in tree stems and woody tissues at sublethal temperatures from fire

    Science.gov (United States)

    Rick G. Kelsey; Douglas J. Westlind

    2017-01-01

    The lethal temperature limit is 60 degrees Celsius (°C) for plant tissues, including trees, with lower temperatures causing heat stress. As fire injury increases on tree stems, there is an accompanying rise in tissue ethanol concentrations, physiologically linked to impaired mitochondrial oxidative phosphorylation energy production. We theorize that sublethal tissue...

  7. GUIDES TO POLLUTION PREVENTION: THE AUTO REPAIR INDUSTRY

    Science.gov (United States)

    Automotive maintenance and repair shops generate a variety of waste streams during activities such as replacing fluids (e.g., motor oil, radiator coolant, transmission fluid, brake fluid), replacing non-repairable parts (e.g., brake shoes/pads, shocks, batteries, belts, mufflers,...

  8. RFID Tracking of Sublethal Effects of Two Neonicotinoid Insecticides on the Foraging Behavior of Apis mellifera

    Science.gov (United States)

    Schneider, Christof W.; Tautz, Jürgen; Grünewald, Bernd; Fuchs, Stefan

    2012-01-01

    The development of insecticides requires valid risk assessment procedures to avoid causing harm to beneficial insects and especially to pollinators such as the honeybee Apis mellifera. In addition to testing according to current guidelines designed to detect bee mortality, tests are needed to determine possible sublethal effects interfering with the animal's vitality and behavioral performance. Several methods have been used to detect sublethal effects of different insecticides under laboratory conditions using olfactory conditioning. Furthermore, studies have been conducted on the influence insecticides have on foraging activity and homing ability which require time-consuming visual observation. We tested an experimental design using the radiofrequency identification (RFID) method to monitor the influence of sublethal doses of insecticides on individual honeybee foragers on an automated basis. With electronic readers positioned at the hive entrance and at an artificial food source, we obtained quantifiable data on honeybee foraging behavior. This enabled us to efficiently retrieve detailed information on flight parameters. We compared several groups of bees, fed simultaneously with different dosages of a tested substance. With this experimental approach we monitored the acute effects of sublethal doses of the neonicotinoids imidacloprid (0.15–6 ng/bee) and clothianidin (0.05–2 ng/bee) under field-like circumstances. At field-relevant doses for nectar and pollen no adverse effects were observed for either substance. Both substances led to a significant reduction of foraging activity and to longer foraging flights at doses of ≥0.5 ng/bee (clothianidin) and ≥1.5 ng/bee (imidacloprid) during the first three hours after treatment. This study demonstrates that the RFID-method is an effective way to record short-term alterations in foraging activity after insecticides have been administered once, orally, to individual bees. We contribute further information on

  9. Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

    Science.gov (United States)

    Ishida, Tokiko; Kotani, Hirokazu; Miyao, Masashi; Kawai, Chihiro; Jemail, Leila; Abiru, Hitoshi; Tamaki, Keiji

    2016-01-01

    The pathogenesis of renal impairment in chronic liver diseases (CLDs) has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy), autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet-fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the pathophysiological mechanisms of

  10. Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

    Directory of Open Access Journals (Sweden)

    Tokiko Ishida

    Full Text Available The pathogenesis of renal impairment in chronic liver diseases (CLDs has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy, autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet-fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the

  11. Lethal and Sublethal Effects of Insecticides on the Egg Parasitoid Telenomus podisi (Hymenoptera: Platygastridae).

    Science.gov (United States)

    Turchen, L M; Golin, V; Butnariu, A R; Guedes, R N C; Pereira, M J B

    2016-02-01

    Insecticide use remains controversial, and subjected to increasing environmental and health concerns, even when recent insecticide groups are considered. Neonicotinoids and even bioinsecticides are in the forefront of discussions regarding their nontarget safety. The ubiquitous focus on the lethal effects of insecticides on nontarget species has been expanding to sublethal effects, as sublethal exposure extends for a longer time and affects a broader range of (nontarget) species. Here we explored the lethal and sublethal effects of a lambda-cyhalothrin + thiamethoxan mixture, the neonicotinoid imidacloprid, and the bioinsecticide azadirachtin on the egg parasitoid Telenomus podisi Ashmead, an important parasitoid of stink bug Euschistus heros (F.), a key soybean pest in neotropical America. Contact with dry insecticide residue on glass surface and (parasitized and healthy) host egg immersion exposure bioassays were performed, assessing their acute lethal effects, and their potential sublethal impairment of parasitism, adult emergence, and fertility of the egg parasitoid. Both imidacloprid and the insecticide mixture exhibited high acute lethal activity toward the parasitoid under contact with dry insecticide residue. These insecticides compromised parasitism and wasp emergence when exposure took place before parasitism. In contrast, azadirachtin did not affect adult survival. However, this bioinsecticide compromised parasitism and progeny production, impairing the female parasitoid reproductive potential. Our results indicate strong negative effects of imidacloprid, and specially of the mixture lambda-cyhalthrin + thiamethoxan. However, even azadirachtin, which exhibited low acute lethality, exhibited significant negative sublethal effects on parasitism and population growth of egg parasitoid, cautioning against their use and the need of semifield and field assessments to confirm such an impact. © The Authors 2015. Published by Oxford University Press on behalf of

  12. [Radiation safety of exploitation of radiation sources at the civil aviation airlines].

    Science.gov (United States)

    Afanas'ev, R V; Zuev, V G; Berezin, G I; Sereda, V N; Zasiad'ko, A K

    2004-01-01

    Radiation risks from isotope-containing equipment, and ionizing and unused X-ray radiation sources are characterized and relevant normative documents with safety requirements to radiation sources installation, radiation safety of aircraft servicing and repair, hand luggage control and heavy luggage registration, personal protection items, system of radiation monitoring at airlines and aircraft works, and liability for breach of performance guidelines are cited.

  13. UV-tolerance and instantaneous physiological stress responses of two Antarctic amphipod species Gondogeneia antarctica and Djerboa furcipes during exposure to UV radiation.

    Science.gov (United States)

    Obermüller, Birgit; Puntarulo, Susana; Abele, Doris

    2007-09-01

    We investigated the shielding against solar ultraviolet radiation and inducible damage, as well as the short-term response of whole animal metabolic rate in two Antarctic shallow water amphipod species. Light absorbance by the carapace of Gondogeneia antarctica and Djerboa furcipes was higher in the UVR (UVB+UVA) range (42.1% and 54.5% on average respectively) compared to the PAR (photosynthetically active radiation) range (38.1% and 50.1% respectively) of the solar spectrum. Bands of higher absorbance correlated with maximal absorbance ranges of sunscreening compounds indicating mycosporine-like amino acids (MAAs) and carotenoids to be innate compounds of the exoskeleton of these species. Though the antioxidant enzyme catalase was photoinhibited, protein damage products did not accumulate under experimental exposure to a daily dose of 6.84 kJ m(-2) d(-1) UVB, 66.24 kJ m(-2) d(-1) UVA and 103.14 kJ m(-2) d(-1) PAR. Animal oxygen consumption during UV-exposure was measured as an indicator of immediate behavioural and physiological stress response. UVB as well as UVA induced a response with altered and highly variable respiratory intensity. Our findings indicate that sub-lethal UVR exposure causes increased oxygen consumption in polar amphipods due to radiation avoidance, shelter seeking behaviour, and presumably also from cellular repair processes.

  14. Management and outcomes of colovesical fistula repair.

    Science.gov (United States)

    Lynn, Elizabeth T; Ranasinghe, Nalin E; Dallas, Kai B; Divino, Celia M

    2012-05-01

    This large retrospective study presents the largest colovesical fistula (CVF) series to date. We report on recurrence risk factors and patient satisfaction based on quality of life after CVF repair. Approval was obtained from The Mount Sinai School of Medicine Institutional Review Board, and a retrospective review was performed from 2003 to 2010 involving 72 consecutive patients who underwent a colovesical fistula repair. The CVF recurrence rate was 11 per cent. Ten percent of our patients who had a history of radiation therapy were at a significantly higher risk of developing a recurrence. Noted recurrence rates were significantly higher in advanced bladder repairs compared with simple repair (P = 0.022). The modified (Gastrointestinal Quality of Life Index) surveys showed overall patient satisfaction score was 3.6, out of a maximum score of 4, regardless of the type of repair or any postoperative complications. Our study found the CVF recurrence rate to be 11 per cent. Patients at higher risk of recurrence include those needing advanced bladder repair, those with "complex" CVF, and those whose fistulas involve the urethra. Patient satisfaction was found to be more closely linked to the resolution of CVF symptoms, irrespective of the type of repair performed or development of postoperative complications.

  15. The radiobiology of laser-driven particle beams: focus on sub-lethal responses of normal human cells

    Science.gov (United States)

    Manti, L.; Perozziello, F. M.; Borghesi, M.; Candiano, G.; Chaudhary, P.; Cirrone, G. A. P.; Doria, D.; Gwynne, D.; Leanza, R.; Prise, K. M.; Romagnani, L.; Romano, F.; Scuderi, V.; Tramontana, A.

    2017-03-01

    Accelerated proton beams have become increasingly common for treating cancer. The need for cost and size reduction of particle accelerating machines has led to the pioneering investigation of optical ion acceleration techniques based on laser-plasma interactions as a possible alternative. Laser-matter interaction can produce extremely pulsed particle bursts of ultra-high dose rates (>= 109 Gy/s), largely exceeding those currently used in conventional proton therapy. Since biological effects of ionizing radiation are strongly affected by the spatio-temporal distribution of DNA-damaging events, the unprecedented physical features of such beams may modify cellular and tissue radiosensitivity to unexplored extents. Hence, clinical applications of laser-generated particles need thorough assessment of their radiobiological effectiveness. To date, the majority of studies have either used rodent cell lines or have focussed on cancer cell killing being local tumour control the main objective of radiotherapy. Conversely, very little data exist on sub-lethal cellular effects, of relevance to normal tissue integrity and secondary cancers, such as premature cellular senescence. Here, we discuss ultra-high dose rate radiobiology and present preliminary data obtained in normal human cells following irradiation by laser-accelerated protons at the LULI PICO2000 facility at Laser Lab Europe, France.

  16. Pectus excavatum repair

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002949.htm Pectus excavatum repair To use the sharing features on this page, please enable JavaScript. Pectus excavatum repair is surgery to correct pectus excavatum . This ...

  17. When "Other" Initiate Repair.

    Science.gov (United States)

    Schegloff, Emanuel A.

    2000-01-01

    Elaborates on the locus of other-initiated repair, and reports on a number of environments in which others initiate repair turns later than the one directly following the trouble-source turn. Describes several ways that other initiation of repair, which occurs in next-turn position, may be delayed within that position. (Author/VWL)

  18. UVc-irradiation sublethal stress does not alter antibiotic susceptibility of staphylococci (MRSA, MSSA, and coagulase-negative staphylococci) to β-lactam, macrolide, and fluoroquinolone antibiotic agents.

    Science.gov (United States)

    Maeda, Yasunori; Goldsmith, Colin E; Coulter, Wilson A; Millar, B Cherie; Dooley, James S G; Lowery, Colm J; Loughrey, Anne; Rooney, Paul J; McDowell, David A; Matsuda, Motoo; Moore, John E

    2012-01-01

    Skin tanning, either by exposure to natural sunlight or through use of UV sunbeds, has become a popular practice in the US, where it is estimated that approximately 1 million times per day someone in the US uses UV radiation for skin tanning, equating to 30 million Americans (circa 10% of the US population) who use a tanning bed. As well as exposing the host to periods of UV radiation, such practices also expose commensal skin bacteria, including Staphylococcus aureus, to such UV radiation. Previous work has indicated that environmental stresses on bacteria may lead to an upregulation of stress responses, in an attempt for the organism to combat the applied stress and remain viable. UV light may act as an environmental stress on bacteria, and so it was the aim of this study to examine the effect of UVc light on the antibiotic susceptibility of commensal skin bacteria, to determine if UV radiation would increase the antibiotic resistance of such skin flora and thus lead to a potential skin flora with increased antibiotic resistance. Previously, it has been shown that UVc light has a greater mutational effect on bacteria compared to lower-energy UV forms, including UVa and UVb light. Therefore, we decided to employ UVc light in our study to amplify the potential for mutational events occurring in skin staphylococci organisms (n=8) including methicillin-sensitive Staphylococcus aureus (n=2), methicillin-resistant Staphylococcus aureus (n=4), and coagulase-negative staphylococci (Staphylococcus haemolyticus) (n=2) were exposed to varying degrees of sublethal radiation via UVc light, and their minimum inhibitory concentration (MIC) susceptibility was determined by broth dilution assay against three classes of commonly used antibiotics, namely β-lactams (penicillin), macrolides (erythromycin), and fluoroquinolones (ciprofloxacin). There was no significant difference between antibiotic susceptibility before UVc exposure and until maximum sublethal stress, prior to cell

  19. Mechanisms of renal cell repair and regeneration after acute renal failure.

    Science.gov (United States)

    Nony, Paul A; Schnellmann, Rick G

    2003-03-01

    In many cases, acute renal failure (ARF) is the result of proximal tubular cell injury and death and can arise in a variety of clinical situations, especially following renal ischemia and drug or toxicant exposure. Although much research has focused on the cellular events leading to ARF, less emphasis has been placed on the mechanisms of renal cell repair and regeneration, although ARF is reversed in over half of those who acquire it. Studies using in vivo and in vitro models have demonstrated the importance of proliferation, migration, and repair of physiological functions of injured renal proximal tubular cells (RPTC) in the reversal of ARF. Growth factors have been shown to produce migration and proliferation of injured RPTC, although the specific mechanisms through which growth factors promote renal regeneration in vivo are unclear. Recently, interactions between integrins and extracellular matrix proteins such as collagen IV were shown to promote the repair of physiological functions in injured RPTC. Specifically, collagen IV synthesis and deposition following cellular injury restored integrin polarity and promoted repair of mitochondrial function and active Na(+) transport. Furthermore, exogenous collagen IV, but not collagen I, fibronectin, or laminin, promoted the repair of physiological functions without stimulating proliferation. These findings suggest the importance of establishing and/or maintaining collagen IV-integrin interactions in the stimulation of repair of physiological functions following sublethal cellular injury. Furthermore, the pathway that stimulates repair is distinct from that of proliferation and migration and may be a viable target for pharmacological intervention.

  20. Cell Radiation Experiment System

    Science.gov (United States)

    Morrison, Dennis R.

    2010-01-01

    The cell radiation experiment system (CRES) is a perfused-cell culture apparatus, within which cells from humans or other animals can (1) be maintained in homeostasis while (2) being exposed to ionizing radiation during controlled intervals and (3) being monitored to determine the effects of radiation and the repair of radiation damage. The CRES can be used, for example, to determine effects of drug, radiation, and combined drug and radiation treatments on both normal and tumor cells. The CRES can also be used to analyze the effects of radiosensitive or radioprotectant drugs on cells subjected to radiation. The knowledge gained by use of the CRES is expected to contribute to the development of better cancer treatments and of better protection for astronauts, medical-equipment operators, and nuclear-power-plant workers, and others exposed frequently to ionizing radiation.

  1. Locomotion Inhibition of Cimex lectularius L. Following Topical, Sublethal Dose Application of the Chitin Synthesis Inhibitor Lufenuron

    Directory of Open Access Journals (Sweden)

    Brittany Campbell

    2017-09-01

    Full Text Available To date, few studies have evaluated chitin synthesis inhibitors against bed bugs, although they would provide an alternative mode of action to circumvent insecticide resistance. Acute and sublethal effects of lufenuron were evaluated against two strains of the common bed bug. Combined acute and sublethal effects were used to calculate effective doses. The dose that was effective against 50% of Harlan strain bed bugs was 0.0081% (w/v, and was much higher against Bradenton strain bed bugs (1.11% w/v. Sublethal doses were chosen to determine the effect that leg abnormalities had on pulling force. Both Harlan and Bradenton strain bed bugs had significantly lower locomotion ability (p < 0.0001 following topical application of lufenuron. The observed sublethal effects that limit locomotion could prevent bed bugs from moving within a domicile and taking a blood meal, subsequently reducing a bed bug population over time.

  2. Percutaneous mitral valve repair.

    Science.gov (United States)

    Gillinov, A Marc; Liddicoat, John R

    2006-01-01

    Surgical mitral valve repair is the procedure of choice to treat mitral regurgitation of all etiologies. Whereas annuloplasty is the cornerstone of mitral valve repair, a variety of other surgical techniques are utilized to correct dysfunction of the leaflets and subvalvular apparatus; in most cases, surgical repair entails application of multiple repair techniques in each patient. Preclinical studies and early human experience have demonstrated that some of these surgical repair techniques can be performed using percutaneous approaches. Specifically, there has been great progress in the development of novel technology to facilitate percutaneous annuloplasty and percutaneous edge-to-edge repair. The objectives of this report were to (1) discuss the surgical foundations for these percutaneous approaches; (2) review device design and experimental and clinical results of percutaneous valve repair; and (3) address future directions, including the key challenges of patient selection and clinical trial design.

  3. Analysis of individual versus group behavior of zebrafish: a model using pH sublethal effects.

    Science.gov (United States)

    Magalhães, Danielly de Paiva; Buss, Daniel Forsin; da Cunha, Rodolfo Armando; Linde-Arias, Ana Rosa; Baptista, Darcilio Fernandes

    2012-06-01

    An image analysis biomonitoring system was used to evaluate sublethal effects of pH on the mean swimming velocity of zebrafish. Responses to stress were tested comparing individual and group responses. Group analysis indicated no effect for all acid pH and for pH 9.0-9.5. Individual analysis indicated behavioral differences for most acid pH and higher than 9.5. Sensitivity to sublethal pH was best assessed when using individual analysis. Zebrafish decreased hyperactivity and increased hypoactivity with more acid or alkaline pH. Individual approach allowed to determine hyperactivity or hypoactivity and the species' thresholds of exposure, which is critical for the management of impairments.

  4. Sublethal concentrations of ichthyotoxic alga Prymnesium parvum affect rainbow trout susceptibility to viral haemorrhagic septicaemia virus

    DEFF Research Database (Denmark)

    Andersen, Nikolaj Gedsted; Lorenzen, Ellen; Boutrup, Torsten Snogdal;

    2016-01-01

    concentrations of the ichthyotoxic alga Prymnesium parvum affect the susceptibility of rainbow trout Oncorhynchus mykiss to viral haemorrhagic septicaemia virus (VHSV). During exposure to sublethal algal concentrations, the fish increased production of mucus on their gills. When fish were exposed to the algae...... for 12 h prior to the addition of virus, a marginal decrease in the susceptibility to VHSV was observed compared to fish exposed to VHSV without algae. If virus and algae were added simultaneously, inclusion of the algae increased mortality by 50% compared to fish exposed to virus only, depending...... on the experimental setup. We concluded that depending on the local exposure conditions, sublethal concentrations of P. parvum could affect susceptibility of fish to infectious agents such as VHSV....

  5. Both genome and cytosol dynamics change in E. coli challenged with sublethal rifampicin

    Science.gov (United States)

    Wlodarski, Michal; Raciti, Bianca; Kotar, Jurij; Cosentino Lagomarsino, Marco; Fraser, Gillian M.; Cicuta, Pietro

    2017-02-01

    While the action of many antimicrobial drugs is well understood at the molecular level, a systems-level physiological response to antibiotics remains largely unexplored. This work considers fluctuation dynamics of both the chromosome and cytosol in Escherichia coli, and their response to sublethal treatments of a clinically important antibiotic, rifampicin. We precisely quantify the changes in dynamics of chromosomal loci and cytosolic aggregates (a rheovirus nonstructural protein known as μNS-GFP), measuring short time-scale displacements across several hours of drug exposure. To achieve this we develop an empirical method correcting for photo-bleaching and loci size effects. This procedure allows us to characterize the dynamic response to rifampicin in different growth conditions, including a customised microfluidic device. We find that sub-lethal doses of rifampicin cause a small but consistent increase in motility of both the chromosomal loci and cytosolic aggregates. Chromosomal and cytosolic responses are consistent with each other and between different growth conditions.

  6. Sublethal doses of imidacloprid disrupt sexual communication and host finding in a parasitoid wasp

    Science.gov (United States)

    Tappert, Lars; Pokorny, Tamara; Hofferberth, John; Ruther, Joachim

    2017-02-01

    Neonicotinoids are widely used insecticides, but their use is subject of debate because of their detrimental effects on pollinators. Little is known about the effect of neonicotinoids on other beneficial insects such as parasitoid wasps, which serve as natural enemies and are crucial for ecosystem functioning. Here we show that sublethal doses of the neonicotinoid imidacloprid impair sexual communication and host finding in the parasitoid wasp Nasonia vitripennis. Depending on the dose, treated females were less responsive to the male sex pheromone or unable to use it as a cue at all. Courtship behaviour of treated couples was also impeded resulting in a reduction of mating rates by up to 80%. Moreover, treated females were no longer able to locate hosts by using olfactory cues. Olfaction is crucial for the reproductive success of parasitoid wasps. Hence, sublethal doses of neonicotinoids might compromise the function of parasitoid wasps as natural enemies with potentially dire consequences for ecosystem services.

  7. Electronic Pathways in Photoactivated Repair of UV Mutated DNA

    Science.gov (United States)

    Bohr, Henrik; Jalkanen, K. J.; Bary Malik, F.

    An investigation of the physics, underlying the damage caused to DNA by UV radiation and its subsequent repair via a photoreactivation mechanism, is presented in this study. Electronic pathways, starting from the initial damage to the final repair process, are presented. UV radiation is absorbed to create a hole-excited thymine or other pyrimidine that subsequently is responsible for the formation of a dimer. The negative-ion of the cofactor riboflavin, FADH-, formed by the exposure of the photolyase protein to visible light, interacts with the hole-excited electronic orbital of the thymine dimer inducing a photon-less Auger transition, which restores the two thymines to the ground state, thereby detaching the lesion and repairing the DNA. Density functional theoretical calculations supporting the theory are presented. The mechanism involves the least amount of energy dissipation and is charge neutral. It also avoids radiation damage in the repair process. Recent experimental data are compatible with this theory.

  8. Impact of prolonged fraction dose-delivery time modeling intensity-modulated radiation therapy on hepatocellular carcinoma cell killing

    Institute of Scientific and Technical Information of China (English)

    Xiao-Kang Zheng; Long-Hua Chen; Xiao Yan; Hong-Mei Wang

    2005-01-01

    AIM: To explore the impact of prolonged fraction dosedelivery time modeling intensity-modulated radiation therapy (IMRT) on cell killing of human hepatocellular carcinoma (HCC) HepG2 and Hep3B cell lines.METHODS: The radiobiological characteristics of human HCC HepG2 and Hep3b cell lines were studied with standard clonogenic assays, using standard linear-quadratic model and incomplete repair model to fit the dose-survival curves. The identical methods were also employed to investigate the biological effectiveness of irradiation protocols modeling clinical conventional fractionated external beam radiotherapy (EBRT, fraction delivery time 3 min) and IMRT with different prolonged fraction delivery time (15, 30, and 45 min). The differences of cell surviving fraction irradiated with different fraction delivery time were tested with paired t-test. Factors determining the impact of prolonged fraction delivery time on cell killing were analyzed.RESULTS: The α/β and repair half-time (T1/2) of HepG2and Hep3b were 3.1 and 7.4 Gy, and 22 and 19 min respectively. The surviving fraction of HepG2 irradiated modeling IMRT with different fraction delivery time was significantly higher than irradiated modeling EBRT and the cell survival increased more pronouncedly with the fraction delivery time prolonged from 15 to 45 min,while no significant differences of cell survival in Hep3b were found between different fraction delivery time protocols.CONCLUSION: The prolonged fraction delivery time modeling IMRT significantly decreased the cell killing in HepG2 but not in Hep3b. The capability of sub-lethal damage repair was the predominant factor determining the cell killing decrease. These effects, if confirmed by clinical studies, should be considered in designing IMRT treatments for HCC.

  9. Kinetics of sarin (GB) following a single sublethal inhalation exposure in the guinea pig.

    Science.gov (United States)

    Whalley, Christopher E; McGuire, Jeffrey M; Miller, Dennis B; Jakubowski, Edward M; Mioduszewski, Robert J; Thomson, Sandra A; Lumley, Lucille A; McDonough, John H; Shih, Tsung-Ming A

    2007-06-01

    To improve toxicity estimates from sublethal exposures to chemical warfare nerve agents (CWNA), it is necessary to generate mathematical models of the absorption, distribution, and elimination of nerve agents. However, current models are based on representative data sets generated with different routes of exposure and in different species and are designed to interpolate between limited laboratory data sets to predict a wide range of possible human exposure scenarios. This study was performed to integrate CWNA sublethal toxicity data in male Duncan Hartley guinea pigs. Specific goal was to compare uptake and clearance kinetics of different sublethal doses of sarin (either 0.1 x or 0.4 x LC50) in blood and tissues of guinea pigs exposed to agent by acute whole-body inhalation exposure after the 60-min LC50 was determined. Arterial catheterization allowed repeated blood sampling from the same animal at various time periods. Blood and tissue levels of acetylcholinesterase, butyrylcholinesterase, and regenerated sarin (rGB) were determined at various time points during and following sarin exposure. The following pharmacokinetic parameters were calculated from the graph of plasma or RBC rGB concentration versus time: time to reach the maximal concentration; maximal concentration; mean residence time; clearance; volume of distribution at steady state; terminal elimination-phase rate constant; and area under plasma concentration time curve extrapolated to infinity using the WinNonlin analysis program 5.0. Plasma and RBC t(1/2) for rGB was also calculated. Data will be used to develop mathematical model of absorption and distribution of sublethal sarin doses into susceptible tissues.

  10. Sublethal Triclosan Exposure Decreases Susceptibility to Gentamicin and Other Aminoglycosides in Listeria monocytogenes

    DEFF Research Database (Denmark)

    Christensen, Ellen Gerd; Gram, Lone; Kastbjerg, Vicky Gaedt

    2011-01-01

    The human food-borne pathogen Listeria monocytogenes is capable of persisting in food processing plants despite cleaning and sanitation and is likely exposed to sublethal biocide concentrations. This could potentially affect susceptibility of the bacterium to biocides and other antimicrobial agen...... is commonly used in listeriosis treatment. The triclosan-induced resistance is, hence, of great concern. Further investigations are needed to determine the molecular mechanisms underlying the effect of triclosan....

  11. The effect of sublethal concentrations of the molluscicide niclosamide on the infectivity of Schistosoma mansoni cercariae.

    Science.gov (United States)

    Ghandour, A M; Webbe, G

    1975-12-01

    Experiments were conducted to assess the effect of sublethal concentrations of niclosamide on the infectivity of Schistosoma mansoni cercariae. Exposure of cercariae to 0.02 mg/l and 0.05 mg/l of niclosamide, respectively, for only two hours increased their mortality during penetration of mammalian host skin. The observed increase in mortality in the skin resulted in a consequent reduction of adult worm recovery from the liver and mesenteric veins of animals infected with the treated cercariae.

  12. Bacterial adaptation to sublethal antibiotic gradients can change the ecological properties of multitrophic microbial communities

    OpenAIRE

    Friman, Ville-Petri; Guzman, Laura Melissa; Reuman, Daniel C.; Bell, Thomas

    2015-01-01

    Antibiotics leak constantly into environments due to widespread use in agriculture and human therapy. Although sublethal concentrations are well known to select for antibiotic-resistant bacteria, little is known about how bacterial evolution cascades through food webs, having indirect effect on species not directly affected by antibiotics (e.g. via population dynamics or pleiotropic effects). Here, we used an experimental evolution approach to test how temporal patterns of antibiotic stress, ...

  13. Radiobiological evaluation of the radiation dose as used in high-precision radiotherapy: effect of prolonged delivery time and applicability of the linear-quadratic model.

    Science.gov (United States)

    Shibamoto, Yuta; Otsuka, Shinya; Iwata, Hiromitsu; Sugie, Chikao; Ogino, Hiroyuki; Tomita, Natsuo

    2012-01-01

    Since the dose delivery pattern in high-precision radiotherapy is different from that in conventional radiation, radiobiological assessment of the physical dose used in stereotactic irradiation and intensity-modulated radiotherapy has become necessary. In these treatments, the daily dose is usually given intermittently over a time longer than that used in conventional radiotherapy. During prolonged radiation delivery, sublethal damage repair takes place, leading to the decreased effect of radiation. This phenomenon is almost universarily observed in vitro. In in vivo tumors, however, this decrease in effect can be counterbalanced by rapid reoxygenation, which has been demonstrated in a laboratory study. Studies on reoxygenation in human tumors are warranted to better evaluate the influence of prolonged radiation delivery. Another issue related to radiosurgery and hypofractionated stereotactic radiotherapy is the mathematical model for dose evaluation and conversion. Many clinicians use the linear-quadratic (LQ) model and biologically effective dose (BED) to estimate the effects of various radiation schedules, but it has been suggested that the LQ model is not applicable to high doses per fraction. Recent experimental studies verified the inadequacy of the LQ model in converting hypofractionated doses into single doses. The LQ model overestimates the effect of high fractional doses of radiation. BED is particularly incorrect when it is used for tumor responses in vivo, since it does not take reoxygenation into account. For normal tissue responses, improved models have been proposed, but, for in vivo tumor responses, the currently available models are not satisfactory, and better ones should be proposed in future studies.

  14. Using video-tracking to assess sublethal effects of pesticides on honey bees (Apis mellifera L.).

    Science.gov (United States)

    Teeters, Bethany S; Johnson, Reed M; Ellis, Marion D; Siegfried, Blair D

    2012-06-01

    Concern about the role of pesticides in honey bee decline has highlighted the need to examine the effects of sublethal exposure on bee behaviors. The video-tracking system EthoVisionXT (Noldus Information Technologies) was used to measure the effects of sublethal exposure to tau-fluvalinate and imidacloprid on honey bee locomotion, interactions, and time spent near a food source over a 24-h observation period. Bees were either treated topically with 0.3, 1.5, and 3 µg tau-fluvalinate or exposed to 0.05, 0.5, 5.0, 50, and 500 ppb imidacloprid in a sugar agar cube. Tau-fluvalinate caused a significant reduction in distance moved at all dose levels (p Bees exposed to 50 and 500 ppb spent significantly more time near the food source than control bees (p bee behavior can enhance current protocols for measuring the effects of pesticides on honey bees at sublethal levels. It may provide a means of identifying problematic compounds for further testing.

  15. Sublethal effects of some botanical and chemical insecticides on the cotton whitefly, Bemisia tabaci (Hem: Aleyrodidae

    Directory of Open Access Journals (Sweden)

    Fatemeh Jafarbeigi

    2014-09-01

    Full Text Available In addition to direct mortalities caused by acute concentrations of insecticides, some biological traits of target pests may be also affected by sublethal doses. The cotton whitefly, Bemisia tabaci (Hem: Aleyrodidae is an important pest of a wide variety of agricultural crops across the world. The control of B. tabaci largely relies on wide application of chemical insecticides. In this study, we analyzed the life table parameters to evaluate the sublethal effect of three plant-derived insecticides (Fumaria parviflora (Fumariaceae, Teucrium polium (Lamiaceae, and Thymus vulgaris (Lamiaceae and two chemical insecticides (pymetrozin and neemarin on B. tabaci. The whiteflies were allowed to oviposit on plants infected with each of the five insecticides using leaf-dip method. The data were analyzed using the age-stage two-sex life table. We found significant differences in the gross reproductive rate (GRR, the net reproductive rat (R0, the intrinsic rate of increase (r and the finite rate of increase (λ of treated whiteflies compared to control. Our results showed that some biological traits of B. tabaci are affected by sub-lethal doses of the plant-derived extracts and that these effects are comparable to those of chemical insecticides. Given the detrimental effects of chemical insecticides on human, environment and non-target organisms, plant-derived insecticides may provide valuable environmentally friendly tools for pest management programs.

  16. Effect of non-homogenous thermal stress during sub-lethal photodynamic antimicrobial chemotherapy

    Science.gov (United States)

    Gadura, N.; Kokkinos, D.; Dehipawala, S.; Cheung, E.; Sullivan, R.; Subramaniam, R.; Schneider, P.; Tremberger, G., Jr.; Holden, T.; Lieberman, D.; Cheung, T.

    2012-03-01

    Pathogens could be inactivated via a light source coupled with a photosensitizing agent in photodynamic antimicrobial chemotherapy (PACT). This project studied the effect of non-homogenous substrate on cell colony. The non-homogeneity could be controlled by iron oxide nano-particles doping in porous glassy substrates such that each cell would experience tens of hot spots when illuminated with additional light source. The substrate non-homogeneity was characterized by Atomic Force Microscopy, Transmission Electron Microscopy and Extended X-Ray Absorption Fine Structure at Brookhaven Synchrotron Light Source. Microscopy images of cell motion were used to study the motility. Laboratory cell colonies on non-homogenous substrates exhibit reduced motility similar to those observed with sub-lethal PCAT treatment. Such motility reduction on non-homogenous substrate is interpreted as the presence of thermal stress. The studied pathogens included E. coli and Pseudomonas aeruginosa. Non-pathogenic microbes Bacillus subtilis was also studied for comparison. The results show that sub-lethal PACT could be effective with additional non-homogenous thermal stress. The use of non-uniform illumination on a homogeneous substrate to create thermal stress in sub-micron length scale is discussed via light correlation in propagation through random medium. Extension to sub-lethal PACT application complemented with thermal stress would be an appropriate application.

  17. Chronic Sublethal Effects of Cantharidin on the Diamondback Moth Plutella xylostella (Lepidoptera: Plutellidae

    Directory of Open Access Journals (Sweden)

    Zhengyu Huang

    2015-05-01

    Full Text Available The diamondback moth, Plutella xylostella (Linnaeus (Lepidoptera: Plutellidae, is a major pest of cruciferous vegetables worldwide. Cantharidin, a natural toxin isolated from blister beetles, has been reported to be toxic to P. xylostella. However, little is known on the chronic sublethal effects of cantharidin on this species. In this study, we assessed the changes of susceptibility, development, reproduction and other demographic parameters in both the selected P. xylostella strain (Sub, selected by LC25 cantharidin for consecutive 12 generations and the revertant strain (SubR, derived from the Sub strain without being exposed to cantharidin for 12 generations. Results revealed that the two strains maintained a relatively high-level susceptibility to cantharidin. Severe adverse effects on the population dynamics and fitness in Sub strain were observed. In addition, repeated exposure of P. xylostella to sublethal concentration of cantharidin resulted in negative effects on adult performance and deformities in adults. Although morphologically normal for individuals, the SubR strain exhibited a disadvantage in population growth rate. Our results showed that sublethal concentration of cantharidin exhibited severe negative effects on population growth for longtime. These findings would be useful for assessing the potential effects and risk of cantharidin on P. xylostella and for developing effective integrated pest management.

  18. Effects of sublethal irradiation on patterns of engraftment after murine bone marrow transplantation.

    Science.gov (United States)

    Andrade, Jacob; Ge, Shundi; Symbatyan, Goar; Rosol, Michael S; Olch, Arthur J; Crooks, Gay M

    2011-05-01

    Attempts to reduce the toxicity of hematopoietic stem cell transplantation have led to the use of various immunosuppressive, yet nonmyeloablative preparative regimens that often include low-dose irradiation. To determine the effects of low-dose irradiation on the dynamics of donor cell engraftment after bone marrow transplantation (BMT), we coupled standard endpoint flow cytometric analysis with in vivo longitudinal bioluminescence imaging performed throughout the early (bone marrow. Flow cytometric analysis showed that sublethal doses of total body irradiation (TBI) significantly increased long-term (14 weeks) donor chimerism in the bone marrow compared with nonirradiated recipients (P bone marrow, confirming that sublethal irradiation does not enhance marrow chimerism early after transplantation. Local irradiation also significantly increased late (but not early) donor chimerism in the irradiated limb. Intrafemoral injection of donor cells provided efficient early chimerism in the injected limb, but long-term systemic donor chimerism was highest with i.v. administration (P marrow space. These findings suggest that the major effect of sublethal irradiation is to enhance long-term donor chimerism by inducing proliferative signals after the initial phase of homing.

  19. Acute toxicity and sublethal effects of fipronil on detoxification enzymes in juvenile zebrafish (Danio rerio).

    Science.gov (United States)

    Wu, Haihua; Gao, Cuie; Guo, Yaping; Zhang, Yuping; Zhang, Jianzhen; Ma, Enbo

    2014-10-01

    The acute toxicity of fipronil and its sublethal effects on detoxification enzymes (carboxylesterases (CarEs), glutathione S-transferases (GSTs), and 7-ethoxycoumarin O-deethylase (ECOD)) in zebrafish (Danio rerio) were investigated. The results indicated that the 24-h LC50 of fipronil for zebrafish was 220.4 μg/L (95% CI: 173.7-272.4 μg/L). Sublethal concentrations of fipronil did not cause significant changes in CarEs activities. In the liver and muscle tissues, GST activities at the tested concentrations did not significantly differ from those in the control. In the brain and gill tissues, GST activities at a concentration of 4 μg/L were significantly lower than those at a concentration of 2 μg/L. The results suggest that CarEs and GSTs were not suitable biomarkers for fipronil effects in D. rerio. A significant induction in the ECOD activities in the brain, gill, liver, and muscle tissues was observed compared with the control. Moreover, the dose-dependent responses of the ECOD activity were observed after treatment with sublethal concentrations of fipronil in the range of 2-20 μg/L. The results suggested that ECOD could be a suitable biomarker of fipronil effects in D. rerio.

  20. Metabolomic responses to sublethal contaminant exposure in neonate and adult Daphnia magna.

    Science.gov (United States)

    Wagner, Nicole D; Simpson, André J; Simpson, Myrna J

    2017-04-01

    The use of consumer products and pharmaceuticals that act as contaminants entering waterways through runoff and wastewater effluents alters aquatic ecosystem health. Traditional toxicological endpoints may underestimate the toxicity of contaminants, as lethal concentrations are often orders of magnitude higher than those found within freshwater ecosystems. While newer techniques examine the metabolic responses of sublethal contaminant exposure, there has been no direct comparison with ontogeny in Daphnia. It was hypothesized that Daphnia magna would have distinct metabolic changes after 3 different sublethal contaminant exposures, because of differences in the toxic mode of action and ontogeny. To test this hypothesis, the proton nuclear magnetic resonance metabolomic profiles were measured in D. magna aged day 0 and 18 after exposure to 28% of the lethal concentration of 50% of organisms tested (LC50) of atrazine, propranolol, and perfluorooctanesulfonic acid (PFOS) for 48 h. Principal component analysis revealed significant separation of contaminants from the control daphnids in both neonates and adults exposed to propranolol and PFOS. In contrast, atrazine exposure caused separation from the controls in only the adult D. magna. Minimal ontogenetic changes in the targeted metabolites were seen after exposure to propranolol. For both atrazine and PFOS exposures ontogeny exhibited unique changes in the targeted metabolites. These results indicate that, depending on the contaminant studied, neonates and adults respond uniquely to sublethal contaminant exposure. Environ Toxicol Chem 2017;36:938-946. © 2016 SETAC. © 2016 SETAC.

  1. Assessment of the sublethal toxicity of organochlorine pesticide endosulfan in juvenile common carp (Cyprinus carpio).

    Science.gov (United States)

    Salvo, Lígia M; Bainy, Afonso C D; Ventura, Eliana C; Marques, Maria R F; Silva, José Roberto M C; Klemz, Cláudio; Silva de Assis, Helena C

    2012-01-01

    This study is aimed at evaluating the sublethal effects of endosulfan (EDS) in juvenile common carp (Cyprinus carpio). For this purpose, fish were exposed for 15 days to the technical EDS (95% pure) diluted in dimethyl sulfoxide (DMSO) 0.1% of the total volume in water solution in a semi-static system at sublethal concentration (1 μg/L). Subsequently, the liver somatic index (LSI) and factor condition (K) were determined. The total cytocrome P450 (CYP), CYP1A isoform, and the ethoxyresorufin-O-deethylase (EROD) activity were determined from the hepatic microsomal fraction as well as the activity of the oxidative stress enzyme system such as superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GP(X)), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PDH). Among the parameters assessed, EDS at the sublethal concentration in subchronic exposure caused significant changes in liver somatic indices as well as induction of the phase I biotransformation system and oxidative stress in juvenile common carp (Cyprinus carpio). Thus, it is seen that the use of biochemical biomarkers of environmental contamination in this study proved to be an extremely important tool for detecting the adverse effects of xenobiotics in the aquatic environment, even at low concentration.

  2. Repeated exposure to sublethal doses of the organophosphorus compound VX activates BDNF expression in mouse brain.

    Science.gov (United States)

    Pizarro, Jose M; Chang, Wenling E; Bah, Mariama J; Wright, Linnzi K M; Saviolakis, George A; Alagappan, Arun; Robison, Christopher L; Shah, Jinesh D; Meyerhoff, James L; Cerasoli, Douglas M; Midboe, Eric G; Lumley, Lucille A

    2012-04-01

    The highly toxic organophosphorus compound VX [O-ethyl S-[2-(diisopropylamino)ethyl]methylphosphonate] is an irreversible inhibitor of the enzyme acetylcholinesterase (AChE). Prolonged inhibition of AChE increases endogenous levels of acetylcholine and is toxic at nerve synapses and neuromuscular junctions. We hypothesized that repeated exposure to sublethal doses of VX would affect genes associated with cell survival, neuronal plasticity, and neuronal remodeling, including brain-derived neurotrophic factor (BDNF). We examined the time course of BDNF expression in C57BL/6 mouse brain following repeated exposure (1/day × 5 days/week × 2 weeks) to sublethal doses of VX (0.2 LD(50) and 0.4 LD(50)). BDNF messenger RNA expression was significantly (p VX exposure. BDNF protein expression, however, was only increased in the CA3 region of the hippocampus. Whether increased BDNF in response to sublethal doses of VX exposure is an adaptive response to prevent cellular damage or a precursor to impending brain damage remains to be determined. If elevated BDNF is an adaptive response, exogenous BDNF may be a potential therapeutic target to reduce the toxic effects of nerve agent exposure.

  3. Determination of the adaptive response induced In vivo by gamma radiation and its relation with the sensibility to the damage induction in the DNA and with the repairing capacity; Determinacion de la respuesta adaptativa inducida In vivo por radiacion gamma y su relacion con la sensibilidad a la induccion de dano en el ADN y con la capacidad de reparacion

    Energy Technology Data Exchange (ETDEWEB)

    Mendiola C, M.T

    2002-07-01

    The kinetics of damage induction and repair at different doses as well as the adaptive response induced by gamma ray exposure were determined in murine leukocytes in vivo. The damage-repair kinetics were established after the exposure to 0.5, 1.0 or 2.0 Gy in a {sup 137}Cs source. Peripheral blood samples were obtained from the tails of mice, the percentage of damaged cells and the DNA migration in each one were analyzed by the single cell gel electrophoresis (SCG) technique or comet assay. Results indicated that there was an induction of approximately 75% comets with the doses of 1.0 and 2.0 Gy, which was considerably reduced to 22% and 42% respectively during the first 15 minutes. This evidences the presence of a rapid repair process and suggests that leucocytes are genetically well prepared to repair this kind of damage. After 15 minutes, a second increase in the percentage of damaged cells that was proportional to dose occurred, which seems to represent the breaks produced during the repair of other kind of lesions. After that a second reduction was observed, reaching values near to the basal ones, except with the dose of 2.0 Gy. The kinetics obtained with the dose of 0.5 Gy was similar to that established with 1.0 Gy, but in this case the initial damage was 50 % lower. Besides, the adaptive response was observed after the exposure of the mice to an adaptive dose of 0.01 Gy and to a challenge dose of 1.0 Gy 60 minutes later. The pretreatment reduced the percentage of damaged cells caused by the challenge dose to one third approximately, and also diminished this parameter produced during the late repair process. This indicates that the early adaptive response is caused, instead of by an increment in repair, by the induction of a process that protects DNA from damage induction by radiation, i.e synthesis of substances that increase the scavenging of free radicals. (Author)

  4. Optimality in DNA repair.

    Science.gov (United States)

    Richard, Morgiane; Fryett, Matthew; Miller, Samantha; Booth, Ian; Grebogi, Celso; Moura, Alessandro

    2012-01-07

    DNA within cells is subject to damage from various sources. Organisms have evolved a number of mechanisms to repair DNA damage. The activity of repair enzymes carries its own risk, however, because the repair of two nearby lesions may lead to the breakup of DNA and result in cell death. We propose a mathematical theory of the damage and repair process in the important scenario where lesions are caused in bursts. We use this model to show that there is an optimum level of repair enzymes within cells which optimises the cell's response to damage. This optimal level is explained as the best trade-off between fast repair and a low probability of causing double-stranded breaks. We derive our results analytically and test them using stochastic simulations, and compare our predictions with current biological knowledge.

  5. Normal tissue tolerance to external beam radiation therapy: Spinal cord; Tolerance a l'irradiation des tissus sains: moelle epiniere

    Energy Technology Data Exchange (ETDEWEB)

    Habrand, J.L. [Departement de radiotherapie, institut Gustave-Roussy, 94 - Villejuif (France); Centre de protontherapie, institut Curie, 91 - Orsay (France); Drouet, F. [Departement de radiotherapie, centre Rene-Gauducheau, 44 - Nantes (France)

    2010-07-15

    Radiation myelopathy is one of the most dreadful complications of radiation therapy. Despite multiple animal experiments and human autopsic series, its pathogenesis remains largely unknown. In most instances, the classical aspect of myelomalacia combines glial and vascular injuries in various sequences. Recent studies point out the role of oligo-dendrocytes and their precursors, as well as of intercellular mediators (cytokines and stress molecules). The clinical presentation comprises a spectrum of non specific neurological symptoms whose evolution is sometimes regressive but more commonly progressive and life-threatening. Usually, it occurs following a latent period of six months to two years after irradiation of the cervical, thoracic or upper lumbar spine to a dose in excess of 50 Gy, conventionally fractionated. Nonetheless, these typical features can be altered by extrinsic factors, such as hypo fractionation/acceleration of the dose, multiple surgical procedures, chemotherapy especially mega therapy, or neurotoxic drugs. Conversely, hyperfractionated regimens that take into account protracted half-time repair of sublethal damages to the CNS, as well as sophisticated estimates of the dose to the cord and QA programs during the treatment course minimize such risks. (authors)

  6. Radiation damage, repopulation and cell recovery analysis of in vitro tumour cell megacolony culture data using a non-Poissonian cell repopulation TCP model

    Science.gov (United States)

    Stavrev, P.; Weldon, M.; Warkentin, B.; Stavreva, N.; Fallone, B. G.

    2005-07-01

    The effects of radiation damage, tumour repopulation and cell sublethal damage repair and the possibility of extracting information about the model parameters describing them are investigated in this work. Previously published data on two different cultured cell lines were analysed with the help of a tumour control probability (TCP) model that describes tumour cell dynamics properly. Different versions of a TCP model representing the cases of full or partial cell recovery between fractions of radiation, accompanied by repopulation or no repopulation were used to fit the data and were ranked according to statistical criteria. The data analysis shows the importance of the linear-quadratic mechanism of cell damage for the description of the in vitro cell dynamics. In a previous work where in vivo data were analysed, the employment of the single hit model of cell kill and cell repopulation produced the best fit, while ignoring the quadratic term of cell damage in the current analysis leads to poor fits. It is also concluded that more experiments using different fractionation regimes producing diverse data are needed to help model analysis and better ranking of the models.

  7. Relationship between Sublethal Injury and Inactivation of Yeast Cells by the Combination of Sorbic Acid and Pulsed Electric Fields▿

    Science.gov (United States)

    Somolinos, M.; García, D.; Condón, S.; Mañas, P.; Pagán, R.

    2007-01-01

    The objective of this study was to investigate the occurrence of sublethal injury after the pulsed-electric-field (PEF) treatment of two yeasts, Dekkera bruxellensis and Saccharomyces cerevisiae, as well as the relation of sublethal injury to the inactivating effect of the combination of PEF and sorbic acid. PEF caused sublethal injury in both yeasts: more than 90% of surviving D. bruxellensis cells and 99% of surviving S. cerevisiae cells were sublethally injured after 50 pulses at 12 kV/cm in buffer at pHs of both 7.0 and 4.0. The proportion of sublethally injured cells reached a maximum after 50 pulses at 12.0 kV/cm (S. cerevisiae) or 16.5 kV/cm (D. bruxellensis), and it kept constant or progressively decreased at greater electric field strengths and with longer PEF treatments. Sublethally PEF-injured cells showed sensitivity to the presence of sorbic acid at a concentration of 2,000 ppm. A synergistic inactivating effect of the combination of PEF and sorbic acid was observed. Survivors of the PEF treatment were progressively inactivated in the presence of 2,000 ppm of sorbic acid at pH 3.8, with the combined treatments achieving more than log10 5 cycles of dead cells under the conditions investigated. This study has demonstrated the occurrence of sublethal injury after exposure to PEF, so yeast inactivation by PEF is not an all-or-nothing event. The combination of PEF and sorbic acid has proven to be an effective method to achieve a higher level of yeast inactivation. This work contributes to the knowledge of the mechanism of microbial inactivation by PEF, and it may be useful for improving food preservation by PEF technology. PMID:17468278

  8. Repairs of composite structures

    Science.gov (United States)

    Roh, Hee Seok

    Repair on damaged composite panels was conducted. To better understand adhesively bonded repair, the study investigates the effect of design parameters on the joint strength. The design parameters include bondline length, thickness of adherend and type of adhesive. Adhesives considered in this study were tested to measure their tensile material properties. Three types of adhesively bonded joints, single strap, double strap, and single lap joint were considered under changing bondline lengths, thickness of adherend and type of adhesive. Based on lessons learned from bonded joints, a one-sided patch repair method for composite structures was conducted. The composite patch was bonded to the damaged panel by either film adhesive FM-73M or paste adhesive EA-9394 and the residual strengths of the repaired specimens were compared under varying patch sizes. A new repair method using attachments has been suggested to enhance the residual strength. Results obtained through experiments were analyzed using finite element analysis to provide a better repair design and explain the experimental results. It was observed that the residual strength of the repaired specimen was affected by patch length. Method for rapid repairs of damaged composite structures was investigated. The damage was represented by a circular hole in a composite laminated plate. Pre-cured composite patches were bonded with a quick-curing commercial adhesive near (rather than over) the hole. Tensile tests were conducted on specimens repaired with various patch geometries. The test results showed that, among the methods investigated, the best repair method restored over 90% of the original strength of an undamaged panel. The interfacial stresses in the adhesive zone for different patches were calculated in order to understand the efficiencies of the designs of these patch repairs. It was found that the composite patch that yielded the best strength had the lowest interfacial peel stress between the patch and

  9. Simulated microgravity influenced the expression of DNA damage repair genes

    Science.gov (United States)

    Zhang, Meng; Sun, Yeqing; Jiawei, Liu; Wang, Ting

    2016-07-01

    Ionizing radiation and microgravity were considered to be the most important stress factors of space environmental the respective study of the biological effects of the radiation and microgravity carried out earlier, but the interaction of the effects of radiation with microgravity started later, and due to difference of the materials and methods the result of this experiment were not consistent. To further investigate the influence of microgravity on the expression of the radiation damage repair genes, the seed of Arabidopsis (Col) and its gravity-insensitive mutant (PIN2) were exposed to 0.1Gy of the dose of energetic carbon-ion beam radiation (LET = 30KeV / μm), and the germinated seed were than fixed in the 3D random positioning apparatus immediately for a 10-day simulated microgravity. By measuring the deflection angle of root tip and the changes of the expression of Ku70 and RAD51 protein, we investigated the impact of microgravity effect on radiation damage repair systems. The results shown that radiation, microgravity and microgravity with radiation could increase the angle of the root of the Col significantly, but no obvious effect on PIN2 type. The radiation could increase the expression of Ku70 significantly in both Col and PIN2, microgravity does not affect the expression, but the microgravity with radiation could decrease the expression of Ku70. This result shown that the microgravity could influence the radiation damage repair systems in molecular level. Moreover, our findings were important to understand the molecular mechanism of the impact of microgravity effect on radiation damage repair systems in vivo.

  10. Workshop on DNA repair.

    NARCIS (Netherlands)

    A.R. Lehmann (Alan); J.H.J. Hoeijmakers (Jan); A.A. van Zeeland (Albert); C.M.P. Backendorf (Claude); B.A. Bridges; A. Collins; R.P.D. Fuchs; G.P. Margison; R. Montesano; E. Moustacchi; A.T. Natarajan; M. Radman; A. Sarasin; E. Seeberg; C.A. Smith; M. Stefanini (Miria); L.H. Thompson; G.P. van der Schans; C.A. Weber (Christine); M.Z. Zdzienika

    1992-01-01

    textabstractA workshop on DNA repair with emphasis on eukaryotic systems was held, under the auspices of the EC Concerted Action on DNA Repair and Cancer, at Noordwijkerhout (The Netherlands) 14-19 April 1991. The local organization of the meeting was done under the auspices of the Medical Genetic C

  11. Laparoscopic lumbar hernia repair.

    Science.gov (United States)

    Madan, Atul K; Ternovits, Craig A; Speck, Karen E; Pritchard, F Elizabeth; Tichansky, David S

    2006-04-01

    Lumbar hernias are rare clinical entities that often pose a challenge for repair. Because of the surrounding anatomy, adequate surgical herniorraphy is often difficult. Minimally invasive surgery has become an option for these hernias. Herein, we describe two patients with lumbar hernias (one with a recurrent traumatic hernia and one with an incisional hernia). Both of these hernias were successfully repaired laparoscopically.

  12. Detection of Thermal Sublethal Injury in Escherichia coli via the Selective Medium Plating Technique: Mechanisms and Improvements

    Science.gov (United States)

    Espina, Laura; García-Gonzalo, Diego; Pagán, Rafael

    2016-01-01

    In food preservation, the synergistic combination of different technologies aims to maximize the total lethality of the process and minimize the intensity of each hurdle. This is especially the case when at least one of the treatments can cause sublethal (reparable) injury in a great proportion of the population, so that sublethally injured cells can end up being entirely inactivated by the other hurdle(s). The selective medium plating technique (SMPT) is extensively used to enumerate bacterial sublethal injury after inimical treatments, being sodium chloride added to the recovery medium to detect damaged bacterial envelopes. However, little work has been done to explain the reasons for the inability of sublethally injured cells to outgrow in selective agar media, whereas they are able to grow in non-selective agar. In the present paper, the performance of SMPT on Escherichia coli cells after heat treatments is explored by applying different selective agents in the recovery media, using mutants lacking factors involved in osmoregulation, and also by examining the integrity of the cytoplasmic membrane. In view of the results, the possibility of a specific toxic effect of Na+ as the main mechanism under SMPT was discarded, since the same level of sublethal injury was detected using KCl instead of NaCl. The synthesis of the osmoprotectant trehalose determined the maximum osmotolerance of intact cells to the selective agents, but was not crucial in the quantification of sublethal injury. Moreover, for the first time, the extent of sublethal injury detected via SMPT was directly correlated with the physical loss of integrity of the cell membrane in 99.999% of the initial population. This was achieved through statistical analysis of flow cytometry data using propidium iodide-exclusion technique when that dye was added before thermal treatments. The present work confirms the adequacy of SMPT as a tool for detecting the occurrence and quantity of sublethally injured cells

  13. DNA repair protocols

    DEFF Research Database (Denmark)

    Bjergbæk, Lotte

    In its 3rd edition, this Methods in Molecular Biology(TM) book covers the eukaryotic response to genomic insult including advanced protocols and standard techniques in the field of DNA repair. Offers expert guidance for DNA repair, recombination, and replication. Current knowledge of the mechanisms...... that regulate DNA repair has grown significantly over the past years with technology advances such as RNA interference, advanced proteomics and microscopy as well as high throughput screens. The third edition of DNA Repair Protocols covers various aspects of the eukaryotic response to genomic insult including...... recent advanced protocols as well as standard techniques used in the field of DNA repair. Both mammalian and non-mammalian model organisms are covered in the book, and many of the techniques can be applied with only minor modifications to other systems than the one described. Written in the highly...

  14. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Bill Bruce; Nancy Porter; George Ritter; Matt Boring; Mark Lozev; Ian Harris; Bill Mohr; Dennis Harwig; Robin Gordon; Chris Neary; Mike Sullivan

    2005-07-20

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway crossings. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without

  15. Repair of DNA Double-Strand Breaks

    Science.gov (United States)

    Falk, Martin; Lukasova, Emilie; Kozubek, Stanislav

    The genetic information of cells continuously undergoes damage induced by intracellular processes including energy metabolism, DNA replication and transcription, and by environmental factors such as mutagenic chemicals and UV and ionizing radiation. This causes numerous DNA lesions, including double strand breaks (DSBs). Since cells cannot escape this damage or normally function with a damaged genome, several DNA repair mechanisms have evolved. Although most "single-stranded" DNA lesions are rapidly removed from DNA without permanent damage, DSBs completely break the DNA molecule, presenting a real challenge for repair mechanisms, with the highest risk among DNA lesions of incorrect repair. Hence, DSBs can have serious consequences for human health. Therefore, in this chapter, we will refer only to this type of DNA damage. In addition to the biochemical aspects of DSB repair, which have been extensively studied over a long period of time, the spatio-temporal organization of DSB induction and repair, the importance of which was recognized only recently, will be considered in terms of current knowledge and remaining questions.

  16. Enantiospecific sublethal effects of the antidepressant fluoxetine to a model aquatic vertebrate and invertebrate.

    Science.gov (United States)

    Stanley, Jacob K; Ramirez, Alejandro J; Chambliss, C Kevin; Brooks, Bryan W

    2007-08-01

    Many contaminants are chiral compounds with enantiomers that may differ markedly in environmental fate, bioavailability, and toxicity. Enantiospecific environmental fate and ecotoxicological information are lacking for many chiral contaminants. The primary objective of this investigation included an assessment of potential enantiospecific differences in sublethal standardized and behavioral responses of the model organisms Pimephales promelas (teleost) and Daphnia magna (crustacean) to the widely prescribed chiral antidepressant fluoxetine. Endpoints assessed included D. magna immobilization, reproduction, and grazing rate and P. promelas survival, growth, and feeding rate. S-Fluoxetine was found to be more toxic to sublethal standardized and behavioral endpoints in P. promelas, potentially because its primary active metabolite, S-norfluoxetine, is more potent than the same metabolite of R-fluoxetine in mammals. This was not observed for D. magna responses. This differential enantiospecific response between model organisms may have resulted from closer target homology between mammals and fish than between mammals and crustaceans. P. promelas feeding rate, an ecologically relevant and mode-of-action related response, was the most sensitive endpoint tested for R- and S-fluoxetine with 10% effect concentration (EC10) values (+/-SE) of 16.1 (+/-20.2) and 3.7 (+/-4.6) microg l(-1), respectively. Up to a 9.4-fold difference in toxicity between enantiomers was observed; P. promelas growth EC10s (+/-SE) for R- and S-fluoxetine were 132.9 (+/-21.2) and 14.1 (+/-8.1) microg l(-1), respectively. Such differences in sublethal responses to fluoxetine enantiomers suggest that enantiospecific toxicity and mode-of-action related responses that are ecologically relevant (e.g., feeding rate) should be considered in future ecological hazard and risk assessments for chiral contaminants.

  17. Sublethal concentrations of carbapenems alter cell morphology and genomic expression of Klebsiella pneumoniae biofilms.

    Science.gov (United States)

    Van Laar, Tricia A; Chen, Tsute; You, Tao; Leung, Kai P

    2015-03-01

    Klebsiella pneumoniae, a Gram-negative bacterium, is normally associated with pneumonia in patients with weakened immune systems. However, it is also a prevalent nosocomial infectious agent that can be found in infected surgical sites and combat wounds. Many of these clinical strains display multidrug resistance. We have worked with a clinical strain of K. pneumoniae that was initially isolated from a wound of an injured soldier. This strain demonstrated resistance to many commonly used antibiotics but sensitivity to carbapenems. This isolate was capable of forming biofilms in vitro, contributing to its increased antibiotic resistance and impaired clearance. We were interested in determining how sublethal concentrations of carbapenem treatment specifically affect K. pneumoniae biofilms both in morphology and in genomic expression. Scanning electron microscopy showed striking morphological differences between untreated and treated biofilms, including rounding, blebbing, and dimpling of treated cells. Comparative transcriptome analysis using RNA sequencing (RNA-Seq) technology identified a large number of open reading frames (ORFs) differentially regulated in response to carbapenem treatment at 2 and 24 h. ORFs upregulated with carbapenem treatment included genes involved in resistance, as well as those coding for antiporters and autoinducers. ORFs downregulated included those coding for metal transporters, membrane biosynthesis proteins, and motility proteins. Quantitative real-time PCR validated the general trend of some of these differentially regulated ORFs. Treatment of K. pneumoniae biofilms with sublethal concentrations of carbapenems induced a wide range of phenotypic and gene expression changes. This study reveals some of the mechanisms underlying how sublethal amounts of carbapenems could affect the overall fitness and pathogenic potential of K. pneumoniae biofilm cells.

  18. Identification of sublethal toxicants in a BC coastal pulp and paper mill effluent

    Energy Technology Data Exchange (ETDEWEB)

    Eickhoff, C.V.; Pickard, J.; Kinnee, K. [BC Research Inc., Vancouver, BC (Canada); Dwernychuk, W. [Hatfield Consultants Ltd., West Vancouver, BC (Canada); Birkholz, D. [EnviroTest Lab., Edmonton, AB (Canada); Kilback, D. [Pacifica Papers, Powell River, BC (Canada)

    2001-06-01

    BC Research Inc. conducted a toxicity identification evaluation to identify the different compounds comprised in the mill Outfall number 1 effluent. The Environmental Effects Monitoring program had determined that these compounds were responsible for sublethal effects to organisms. Echinoderm species like the sand dollar, Dendraster excentricus Eshscholtz, the purple sea urchin, Stronglyocentrotus purpuratus Stimpson, and the marine algae, Champia parvula had suffered toxicity caused by the mill effluent. The last several Environmental Effects Monitoring testing periods had shown the sublethal toxicity of the Outfall number 1 effluent to echinoderms was very consistent. Based on the high cost and shipping associated with the Champia bioassays, toxicity tests conducted during the peak spawning season of the sea urchin and the non significant difference between the sensitivity of the sand dollar and the purple sea urchin, the purple sea urchin was selected to evaluate the toxicity of the manipulated samples for the tests. The tests conducted were: a baseline toxicity test performed immediately upon receipt of the effluent sample, the pH adjustment filtration test to determine if the toxic compound can be removed using filtration, the pH adjustment aeration test to determine if volatile compounds in the sample are toxic, the pH adjustment solid phase extraction test to determine the level of toxicity from organic compounds and metal chelates that can be removed by solid phase extraction. The results indicated that it seems high molecular weight molecules were responsible for the sublethal toxicity observed. Two different sources could be responsible: lignin derived macromolecules, and polymer compounds used as flocculants and sizing agents. Further testing of the pulp mill effluent to identify the source of the toxic high molecular weight compounds was recommended. 22 refs., 4 tabs., 6 figs.

  19. Contact irritant responses of Aedes aegypti Using sublethal concentration and focal application of pyrethroid chemicals.

    Directory of Open Access Journals (Sweden)

    Hortance Manda

    Full Text Available BACKGROUND: Previous studies have demonstrated contact irritant and spatial repellent behaviors in Aedes aegypti following exposure to sublethal concentrations of chemicals. These sublethal actions are currently being evaluated in the development of a push-pull strategy for Ae. aegypti control. This study reports on mosquito escape responses after exposure to candidate chemicals for a contact irritant focused push-pull strategy using varying concentrations and focal application. METHODS: Contact irritancy (escape behavior, knockdown and 24 hour mortality rates were quantified in populations of female Ae. aegypti under laboratory conditions and validated in the field (Thailand and Peru using experimental huts. Evaluations were conducted using varying concentrations and treatment surface area coverage (SAC of three pyrethroid insecticides: alphacypermethrin, lambacyhalothrin and deltamethrin. RESULTS: Under laboratory conditions, exposure of Ae. aegypti to alphacypermethrin using the standard field application rate (FAR resulted in escape responses at 25% and 50% SAC that were comparable with escape responses at 100% SAC. Significant escape responses were also observed at <100% SAC using ½FAR of all test compounds. In most trials, KD and 24 hour mortality rates were higher in mosquitoes that did not escape than in those that escaped. In Thailand, field validation studies indicated an early time of exit (by four hours and 40% increase in escape using ½FAR of alphacypermethrin at 75% SAC compared to a matched chemical-free control. In Peru, however, the maximum increase in Ae. aegypti escape from alphacypermethrin-treated huts was 11%. CONCLUSIONS/SIGNIFICANCE: Results presented here suggest a potential role for sublethal and focal application of contact irritant chemicals in an Ae. aegypti push-pull strategy to reduce human-vector contact inside treated homes. However, the impact of an increase in escape response on dengue virus transmission is

  20. Sublethal effects on wood frogs chronically exposed to environmentally relevant concentrations of two neonicotinoid insecticides.

    Science.gov (United States)

    Robinson, Stacey A; Richardson, Sarah D; Dalton, Rebecca L; Maisonneuve, France; Trudeau, Vance L; Pauli, Bruce D; Lee-Jenkins, Stacey S Y

    2017-04-01

    Neonicotinoids are prophylactically used globally on a variety of crops, and there is concern for the potential impacts of neonicotinoids on aquatic ecosystems. The intensive use of pesticides on crops has been identified as a contributor to population declines of amphibians, but currently little is known regarding the sublethal effects of chronic neonicotinoid exposure on amphibians. The objective of the present study was to characterize the sublethal effect(s) of exposure to 3 environmentally relevant concentrations (1 μg/L, 10 μg/L, and 100 μg/L) of 2 neonicotinoids on larval wood frogs (Lithobates sylvaticus) using outdoor mesocosms. We exposed tadpoles to solutions of 2 commercial formulations containing imidacloprid and thiamethoxam, and assessed survival, growth, and development. Exposure to imidacloprid at 10 μg/L and 100 μg/L increased survival and delayed completion of metamorphosis compared with controls. Exposure to thiamethoxam did not influence amphibian responses. There was no significant effect of any treatment on body mass or size of the metamorphs. The results suggest that current usage of imidacloprid and thiamethoxam does not pose a threat to wood frogs. However, further assessment of both direct and indirect effects on subtle sublethal endpoints, and the influence of multiple interacting stressors at various life stages, is needed to fully understand the effects of neonicotinoids on amphibians. Environ Toxicol Chem 2017;36:1101-1109. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

  1. Acute toxicities and sublethal effects of some conventional insecticides on Trichogramma chilonis (Hymenoptera: Trichogrammatidae).

    Science.gov (United States)

    Wang, De-Sen; He, Yu-Rong; Guo, Xiang-Ling; Luo, Yong-Li

    2012-08-01

    The acute toxicity of 10 conventional insecticides to adult of Trichogramma chilonis Ishii (Hymenoptera: Trichogrammatidae) was bioassayed by membrane method, and then their sublethal effects on the parasitoid were evaluated in the laboratory. Based on sublethal concentration (LC30) values at 8 h after treatment, we determined that adult T. chilonis were the most susceptible to chlorfenapyr, followed by fipronil, spinosad, avermectins, beta-cypermethrin, and cartap, with lethal concentration (LC)30 values of 0.3133, 0.3269, 1.5408, 3.2961, 6.1469, and 9.021 mg/liter, respectively. The field-recommended concentrations of chlorfluazuron, indoxacarb, Bacillus thuringiensis, and tebufenozide caused Cartap and spinosad also reduced longevity (8 and 7.9 d) and fecundity (110.77 and 117.2) of treated adults, but cartap enhanced the female percentage of F1 offspring (61.6%), resulting a statistical higher R0, r(m), and lambda of treated T. chilonis. In contrast, chlorfluazuron and tebufenozide increased longevity (16.4 and 15.4 d) and fecundity (248 and 256.9) of treated adults but slightly decreased the female percentage of F1 offspring (31.4 and 38.1%). Although chlorfenapyr showed no adverse influence on longevity and fecundity, it remarkably reduced the female percentage of F1 offspring (13.5%), leading to a lower R0, r(m), and lambda of treated T. chilonis. Indoxacarb, B. thuringiensis, and beta-cypermethrin had no obvious sublethal effects on the longevity and fecundity of treated adults. Based on these results, we consider B. thuringienesis, chlorfluazuron, indoxacarb, beta-cypermethrin, and tebufenozide safe to T. chilonis, suggesting that these insecticides are compatible with this parasitoid when being used in the field. However, fipronil, chlorfenapyr, spinosad, and avermectins were very harmful to T. chilonis. Timing of application of these insecticides was critical.

  2. Busulfan administration produces sublethal effects on somatic tissues and inhibits gametogenesis in Senegalese sole juveniles.

    Science.gov (United States)

    Pacchiarini, T; Olague, E; Sarasquete, C; Cabrita, E

    2014-05-01

    Busulfan, a cytotoxic alkylating agent used for treatment of chronic myeloid leukemia has effects in mammalian germ cells. In fish species, the use of this compound is of special interest in intra and interspecies germ cell transplants. To determine the effects of busulfan in fish a previous range finding experiment was designed. Survival and growth rate of 150-days after hatching (150DAH) Senegalese sole (Solea senegalensis) juveniles was determined. In a second experiment, the effects of a sublethal busulfan dose in fish germ cell depletion and in somatic tissues were analysed. Sublethal effects of several busulfan treatments (B10-10 days after injection, B20-20 days after injection, B20÷-20 days after injection with double injection) were determined in somatic and gonadal tissues. Alterations were registered through histopathological techniques, TUNEL (cell apoptosis) and quantified at molecular level (Q-PCR analyses) using the vasa mRNAs (Ssvasa1-2 and Ssvasa3-4 mRNAs) as molecular markers for germinal cells in Senegalese sole juveniles. Several sublethal effects were observed with 40 mg kg⁻¹ busulfan, a non-lethal dose, such as: pyknosis in liver, increase of melanomacrophage centres and blood stagnation in spleen and interruption of gonadal development. Females were more affected by busulfan treatments than males in terms of germ cell disruption, since a significant decrease in the expression of both Ssvasa1-2 and Ssvasa3-4 markers was found in the gonad of treated females rather than males. At 10 days post-treatment (B10), females already presented a decrease in germ cell proliferation, as confirmed by Q-PCR. Ssvasa expression proved to be a reliable tool for the direct evaluation of the effects of busulfan on Senegalese sole gonadal development, proving that busulfan can be a suitable treatment for causing transient sterility in recipient gonads for germ cell transplantation.

  3. Shell growth of unfed oysters in the laboratory: a sublethal bioassay system for pollutants

    Energy Technology Data Exchange (ETDEWEB)

    Conger, K.A.; Swift, M.L.; Reeves, J.B. III; Lakshmanan, S.

    1978-01-16

    Unfed oysters, Crassostrea virginica Gmelin, in 12 g/l commercial grade artificial sea-water supplemented with calcium bicarbonate (approximately 7 mM Ca/sup 2 +/ and HCO/sub 3//sup -/) deposit shell for four to six weeks. A no-growth critical calcium ion concentration of 1.5 mM was determined in this study. A simple sublethal bioassay system can be developed utilizing the observed shell growth. Significant (p < 0.001) inhibition of shell deposition in oysters subjected to an initial concentration of 0.25 mg Cd/sup 2 +//l demonstrates the efficacy of the proposed method.

  4. Listeria monocytogenes' Step-Like Response to Sub-Lethal Concentrations of Nisin.

    Science.gov (United States)

    Takhistov, Paul; George, Bernice; Chikindas, Michael L

    2009-12-01

    Microbial safety of food products is often accomplished by the formulation of food-grade preservatives into the product. Because of the growing consumer demand for natural substances (including preservatives) in the composition of consumed foods, there is also a growing interest in the natural antimicrobial nisin, which has generally recognized as safe (GRAS) status for certain applications. During the products storage time, concentrations of preservative(s) are decreasing, which may eventually cause a serious problem in the food's microbial safety. Here, for the first time we report on the non-linear response of a foodborne pathogen, Listeria monocytogenes, to sub-lethal concentrations of nisin.

  5. Sublethal ammonia exposure of Nile tilapia (Oreochromis niloticus L.): effects on gill, liver and kidney histology.

    Science.gov (United States)

    Benli, Aysel Cağlan Karasu; Köksal, Gülten; Ozkul, Ayhan

    2008-07-01

    The effects of exposures to sublethal ammonia concentrations on Nile tilapia (Oreochromis niloticus L.) were determined with respect to histology. The experiments were conducted for six weeks and with four different ammonia concentrations (control, 1, 2, 5, 10 mg l(-1) TA-N). Fish exposed to different ammonia concentrations displayed histopathologic alterations in the gills, liver and kidney. Gill tissues displayed hyperemia, chloride cell proliferation, fusion in secondary lamella, telangiectasis. Liver tissue revealed cloudy swelling and hydropic degeneration, whereas in kidney tissues hyperemia and glomerulonephritis were observed.

  6. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; George Ritter; Bill Mohr; Matt Boring; Nancy Porter; Mike Sullivan; Chris Neary

    2004-12-31

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway crossings. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without

  7. Disruption of Maternal DNA Repair Increases Sperm-DerivedChromosomal Aberrations

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, Francesco; Essers, Jeroun; Kanaar, Roland; Wyrobek,Andrew J.

    2007-02-07

    The final weeks of male germ cell differentiation occur in aDNA repair-deficient environment and normal development depends on theability of the egg to repair DNA damage in the fertilizing sperm. Geneticdisruption of maternal DNA double-strand break repair pathways in micesignificantly increased the frequency of zygotes with chromosomalstructural aberrations after paternal exposure to ionizing radiation.These findings demonstrate that radiation-induced DNA sperm lesions arerepaired after fertilization by maternal factors and suggest that geneticvariation in maternal DNA repair can modulate the risk of early pregnancylosses and of children with chromosomal aberrations of paternalorigin.

  8. The impact of heterochromatin on DSB repair.

    Science.gov (United States)

    Goodarzi, Aaron A; Noon, Angela T; Jeggo, Penny A

    2009-06-01

    DNA NHEJ (non-homologous end-joining) is the major DNA DSB (double-strand break) repair pathway in mammalian cells. Although NHEJ-defective cell lines show marked DSB-repair defects, cells defective in ATM (ataxia telangiectasia mutated) repair most DSBs normally. Thus NHEJ functions independently of ATM signalling. However, approximately 15% of radiation-induced DSBs are repaired with slow kinetics and require ATM and the nuclease Artemis. DSBs persisting in the presence of an ATM inhibitor, ATMi, localize to heterochromatin, suggesting that ATM is required for repairing DSBs arising within or close to heterochromatin. Consistent with this, we show that siRNA (small interfering RNA) of key heterochromatic proteins, including KAP-1 [KRAB (Krüppel-associated box) domain-associated protein 1], HP1 (heterochromatin protein 1) and HDAC (histone deacetylase) 1/2, relieves the requirement for ATM for DSB repair. Furthermore, ATMi addition to cell lines with genetic alterations that have an impact on heterochromatin, including Suv39H1/2 (suppressor of variegation 3-9 homologue 1/2)-knockout, ICFa (immunodeficiency, centromeric region instability, facial anomalies syndrome type a) and Hutchinson-Guilford progeria cell lines, fails to have an impact on DSB repair. KAP-1 is a highly dose-dependent, transient and ATM-specific substrate, and mutation of the ATM phosphorylation site on KAP-1 influences DSB repair. Collectively, the findings show that ATM functions to overcome the barrier to DSB repair posed by heterochromatin. However, even in the presence of ATM, gamma-H2AX (phosphorylated histone H2AX) foci form on the periphery rather than within heterochromatic centres. Finally, we show that KAP-1's association with heterochromatin is diminished as cells progress through mitosis. We propose that KAP-1 is a critical heterochromatic factor that undergoes specific modifications to promote DSB repair and mitotic progression in a manner that allows localized and transient

  9. DNA repair and mutagenesis of singlestranded bacteriophages

    Energy Technology Data Exchange (ETDEWEB)

    Doubleday, O.P.; Brandenburger, A.; Wagner, R. Jr.; Radman, M. (Brussels Univ. (Belgium)); Godson, G.N.

    1981-01-01

    Virtually all radiation-induced mutagenesis is believed to result from an error-prone repair activity (SOS repair) and to involve mutations occurring both at the site of radiation-induced lesions (targeted mutations) and in undamaged DNA (untargeted mutations). To examine the relative contributions of targeted and untargeted mutations to ..gamma.. and ultraviolet (UV) radiation mutagenesis we have determined the DNA sequences of 174 M13 revertant phages isolated from stocks of irradiated or unirradiated amber mutants grown in irradiated or unirradiated host bacteria. We have detected no obvious specificity of mutagenesis and find no evidence of a predominance of targeted mutations associated with either UV- or ..gamma..-irradiation of the phages or with the induction of the host SOS repair system. In particular, pyrimidine dimers do not appear to be the principal sites of UV-induced bare substitution mutagenesis, suggesting that such UV-induced mutagenesis may be untargeted or occur at sites of lesions other than pyrimidine dimers.

  10. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; George Ritter; Bill Mohr; Matt Boring; Nancy Porter; Mike Sullivan; Chris Neary

    2004-08-17

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without liners

  11. Salvage hypospadias repairs

    Directory of Open Access Journals (Sweden)

    Sripathi V

    2008-01-01

    Full Text Available Aim: Review of our experience and to develop an algorithm for salvage procedures in the management of hypospadias cripples and treatment of urethral strictures following hypospadias repair. Methods: This is a retrospective review of hypospadias surgeries over a 41-month period. Out of a total 168 surgeries, 20 were salvage/re-operative repairs. In three children a Duplay repair was feasible, while in four others a variety of single-stage repairs could be done. The repair was staged in seven children - buccal mucosal grafts (BMGs in five, buccal mucosal tube in one, and skin graft in one. Five children with dense strictures were managed by dorsal BMG inlay grafting in one, vascularized tunical onlay grafting on the ventrum in one, and a free tunical patch in one. Three children were treated by internal urethrotomy and stenting for four weeks with a poor outcome. Results: The age of children ranged from 1.5-15 years (mean 4.5. Follow-up ranged from 3 months to 3.5 years. Excellent results were obtained in 10 children (50% with a well-surfaced erect penis and a slit-like meatus. Glans closure could not be achieved and meatus was coronal in three. Two children developed fistulae following a Duplay repair and following a staged BMG. Three repairs failed completely - a composite repair broke down, a BMG tube stenosed with a proximal leak, and a stricture recurred with loss of a ventral free tunical graft. Conclusions: In salvage procedures performed on hypospadias cripples, a staged repair with buccal mucosa as an inlay in the first stage followed by tubularization 4-6 months later provides good results. A simple algorithm to plan corrective surgery in failed hypospadias cases and obtain satisfactory results is devised.

  12. Radiological assessment of steam generator repair and replacement

    Energy Technology Data Exchange (ETDEWEB)

    Parkhurst, M.A.; Rathbun, L.A.; Murphy, D.W.

    1983-12-01

    Previous analyses of the radiological impact of removing and replacing corroded steam generators have been updated based on experience at Surry Units 1 and 2 and Turkey Point Units 3 and 4. The sleeving repairs of degraded tubes at San Onofre Unit 1, Point Beach Unit 2, and R.E. Ginna are also analyzed. Actual occupational doses incurred during application of the various technologies used in repairs have been included, along with radioactive waste quantities and constituents. Considerable progress has been made in improving radiation protection and reducing worker dose by the development of remotely controlled equipment and the implementation of dose reduction strategies that have been successful in previous repair operations.

  13. Assessment of Potential Sublethal Effects of Various Insecticides on Key Biological Traits of The Tobacco Whitefly, Bemisia tabaci

    Science.gov (United States)

    He, Yuxian; Zhao, Jianwei; Zheng, Yu; Weng, Qiyong; Biondi, Antonio; Desneux, Nicolas; Wu, Kongming

    2013-01-01

    The tobacco whitefly Bemisia tabaci is one of the most devastating pests worldwide. Current management of B. tabaci relies upon the frequent applications of insecticides. In addition to direct mortality by typical acute toxicity (lethal effect), insecticides may also impair various key biological traits of the exposed insects through physiological and behavioral sublethal effects. Identifying and characterizing such effects could be crucial for understanding the global effects of insecticides on the pest and therefore for optimizing its management in the crops. We assessed the effects of sublethal and low-lethal concentrations of four widely used insecticides on the fecundity, honeydew excretion and feeding behavior of B. tabaci adults. The probing activity of the whiteflies feeding on treated cotton seedlings was recorded by an Electrical Penetration Graph (EPG). The results showed that imidacloprid and bifenthrin caused a reduction in phloem feeding even at sublethal concentrations. In addition, the honeydew excretions and fecundity levels of adults feeding on leaf discs treated with these concentrations were significantly lower than the untreated ones. While, sublethal concentrations of chlorpyrifos and carbosulfan did not affect feeding behavior, honeydew excretion and fecundity of the whitefly. We demonstrated an antifeedant effect of the imidacloprid and bifenthrin on B. tabaci, whereas behavioral changes in adults feeding on leaves treated with chlorpyrifos and carbosulfan were more likely caused by the direct effects of the insecticides on the insects' nervous system itself. Our results show that aside from the lethal effect, the sublethal concentration of imidacloprid and bifenthrin impairs the phloem feeding, i.e. the most important feeding trait in a plant protection perspective. Indeed, this antifeedant property would give these insecticides potential to control insect pests indirectly. Therefore, the behavioral effects of sublethal concentrations of

  14. Assessment of potential sublethal effects of various insecticides on key biological traits of the tobacco whitefly, Bemisia tabaci.

    Science.gov (United States)

    He, Yuxian; Zhao, Jianwei; Zheng, Yu; Weng, Qiyong; Biondi, Antonio; Desneux, Nicolas; Wu, Kongming

    2013-01-01

    The tobacco whitefly Bemisia tabaci is one of the most devastating pests worldwide. Current management of B. tabaci relies upon the frequent applications of insecticides. In addition to direct mortality by typical acute toxicity (lethal effect), insecticides may also impair various key biological traits of the exposed insects through physiological and behavioral sublethal effects. Identifying and characterizing such effects could be crucial for understanding the global effects of insecticides on the pest and therefore for optimizing its management in the crops. We assessed the effects of sublethal and low-lethal concentrations of four widely used insecticides on the fecundity, honeydew excretion and feeding behavior of B. tabaci adults. The probing activity of the whiteflies feeding on treated cotton seedlings was recorded by an Electrical Penetration Graph (EPG). The results showed that imidacloprid and bifenthrin caused a reduction in phloem feeding even at sublethal concentrations. In addition, the honeydew excretions and fecundity levels of adults feeding on leaf discs treated with these concentrations were significantly lower than the untreated ones. While, sublethal concentrations of chlorpyrifos and carbosulfan did not affect feeding behavior, honeydew excretion and fecundity of the whitefly. We demonstrated an antifeedant effect of the imidacloprid and bifenthrin on B. tabaci, whereas behavioral changes in adults feeding on leaves treated with chlorpyrifos and carbosulfan were more likely caused by the direct effects of the insecticides on the insects' nervous system itself. Our results show that aside from the lethal effect, the sublethal concentration of imidacloprid and bifenthrin impairs the phloem feeding, i.e. the most important feeding trait in a plant protection perspective. Indeed, this antifeedant property would give these insecticides potential to control insect pests indirectly. Therefore, the behavioral effects of sublethal concentrations of

  15. Multiple sublethal chemicals negatively affect tadpoles of the green frog, Rana clamitans

    Science.gov (United States)

    Boone, Michelle D.; Bridges, Christine M.; Fairchild, James F.; Little, Edward E.

    2005-01-01

    Many habitats may be exposed to multiple chemical contaminants, particularly in agricultural areas where fertilizer and pesticide use are common; however, the singular and interactive effects of contaminants are not well understood. The objective of our study was to examine how realistic, sublethal environmental levels of ammonium nitrate fertilizer (0, 10, 20 mg/L and ammonium chloride control) and the common insecticide carbaryl (0 or 2.5 mg/L) individually and interactively affect the development, size, and survival of green frog (Rana clamitans) tadpoles. We reared tadpoles for 95 d in outdoor 1,000-L polyethylene ponds. We found that the combination of carbaryl and nitrate had a negative effect on development and mass of tadpoles compared to the positive effect that either contaminant had alone. Presence of carbaryl was generally associated with short-term increases in algal resources, including ponds exposed to both carbaryl and nitrate. However, with exposure to nitrate and carbaryl, tadpole mass and development were not positively affected as with one chemical stressor alone. The combination of these sublethal contaminants may reduce the ability of amphibians to benefit from food-rich environments or have metabolic costs. Our study demonstrates the importance of considering multiple stressors when evaluating population-level responses.

  16. Can damselfly larvae (Ischnura elegans) be used as bioindicators of sublethal effects of environmental contamination?

    Science.gov (United States)

    Van Praet, Nander; De Bruyn, Luc; De Jonge, Maarten; Vanhaecke, Lynn; Stoks, Robby; Bervoets, Lieven

    2014-09-01

    The present study measured various pesticides and trace metals, together with sublethal effect biomarkers (lipid, protein and glycogen levels, acetylcholinesterase (AChE) and glutathione-S-transferase (GST) activities) in damselfly larvae (Ischnura elegans) at sixteen sampling sites in Flanders (Belgium). Four pesticides (chloridazon, dichlorvos, terbutylazine, metolachlor), some of them hardly measurable in surface water, and all trace metals were above the limit of quantification in damselfly tissue. A principal component analysis (PCA) on the accumulated pollutant concentrations returned five pollutant axes explaining 85.8% of the total variation. Based on these PCA-axes a hierarchical cluster analysis revealed that the 16 sampled ponds could be classified in 7 groups. Increasing dichlorvos levels in the animals resulted in a lower body mass. Body mass was negatively correlated with GST and AChE activities, lipid and glycogen levels. The present findings provide evidence of toxicity-induced sublethal stress of dichlorvos accumulation in natural populations of I. elegans. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Effects of Sublethal Doses of Imidacloprid on Young Adult Honeybee Behaviour.

    Directory of Open Access Journals (Sweden)

    Carolina Mengoni Goñalons

    Full Text Available Imidacloprid (IMI, a neonicotinoid used for its high selective toxicity to insects, is one of the most commonly used pesticides. However, its effect on beneficial insects such as the honeybee Apis mellifera L is still controversial. As young adult workers perform in-hive duties that are crucial for colony maintenance and survival, we aimed to assess the effect of sublethal IMI doses on honeybee behaviour during this period. Also, because this insecticide acts as a cholinergic-nicotinic agonist and these pathways take part in insect learning and memory processes; we used IMI to assess their role and the changes they suffer along early adulthood. We focused on appetitive behaviours based on the proboscis extension response. Laboratory reared adults of 2 to 10 days of age were exposed to sublethal IMI doses (0.25 or 0.50ng administered orally or topically prior to behavioural assessment. Modification of gustatory responsiveness and impairment of learning and memory were found as a result of IMI exposure. These outcomes differed depending on age of evaluation, type of exposure and IMI dose, being the youngest bees more sensitive and the highest oral dose more toxic. Altogether, these results imply that IMI administered at levels found in agroecosystems can reduce sensitivity to reward and impair associative learning in young honeybees. Therefore, once a nectar inflow with IMI traces is distributed within the hive, it could impair in-door duties with negative consequences on colony performance.

  18. Sublethal Dose of Diazinon Induces Pulmonary Toxicity in Rat: Histopathological Evidence

    Directory of Open Access Journals (Sweden)

    Gholamreza Najafi

    2014-02-01

    Full Text Available Objective: Diazinon (DZ is a widely used contact organophosphorous pesticide with broad spectrum insecticide activity. The extensive use of DZ has caused great concern due to the hazardous side effects on human beings as well as wild and domestic animals. The aim of this study was to investigate the effect of sublethal dose of DZ on rat lung. Material and methods: Seven groups of male Wistar rats were used comprising control and test groups. The control group received corn oil (0.3 ml/day for 60 days by oral gavages. The test groups received DZ at a dose of 60 mg/kg body weight orally for 2, 10, 24, 30, 54 and 60 days, respectively. Results: The histopathological analysis of the lungs in DZ-treated groups revealed congestion on day 2, pulmonary edema and emphysema on day 10, congestion and atelectasia on day 24, infiltration of mononuclear cells on day 30 and pulmonary hemorrhage along with bronchial glands hyperplasia on days 54 and 60. DZ administration also caused a significant decrease in serum cholinesterase activity in a time-dependent manner. Conclusion: These findings indicate that sublethal dose of DZ can induce severe lesions in the lung of rat. [J Interdiscipl Histopathol 2014; 2(1.000: 26-31

  19. Lethal and sublethal effects of cyantraniliprole on Bactrocera dorsalis (Hendel) (Diptera: Tephritidae).

    Science.gov (United States)

    Zhang, Ruimin; Jang, Eric B; He, Shiyu; Chen, Jiahua

    2015-02-01

    The oriental fruit fly, Bactrocera dorsalis (Hendel), is one of the most globally important insect pests. Studies were conducted with the novel anthranilic diamide insecticide cyantraniliprole to determine its lethal and sublethal effects on B. dorsalis. An ingestion toxicity bioassay showed that cyantraniliprole was active against B. dorsalis, and the 72 h feeding LC50 was 3.22 µg g(-1) in adult diet for a susceptible strain. Sublethal doses of cyantraniliprole (1.30 µg g(-1) adult diet) induced a hormesis effect on B. dorsalis. The mating competitiveness of B. dorsalis treated with cyantraniliprole at 3.27 µg g(-1) adult diet was significantly lower when compared with the controls. The lower dose (1.30 µg g(-1) adult diet) of cyantraniliprole improved the total mating times of both mating pairs in treated groups and also the mating competitiveness of the treated males when compared with the higher dose and controls. Cyantraniliprole-treated females of the mated pairs with the lower dose laid more eggs. On the fifth day, female receptivity in the treated group was significantly reduced when compared with the controls. These results indicate that cyantraniliprole is effective against B. dorsalis. The inhibition and stimulation effect of cyantraniliprole on the adult's mating performance at different concentrations was proved. © 2014 Society of Chemical Industry.

  20. Dimethylformamide improves the in vitro characteristics of thawed stallion spermatozoa reducing sublethal damage.

    Science.gov (United States)

    Morillo Rodriguez, A; Balao da Silva, C; Macías-García, B; Gallardo Bolaños, J M; Tapia, J A; Aparicio, I M; Ortega-Ferrusola, C; Peña, F J

    2012-12-01

    A total of 42 ejaculates were used in the experiment; six ejaculates per stallion, obtained from seven Pure Spanish stallions (PRE), were split and frozen in freezing media with different concentrations and combinations of cryoprotectant (CPA): (i) Cáceres (skim milk based extender) containing 2.5% glycerol (2.5GL), (ii) Cáceres containing 1.5% glycerol and 1.5% dimethylformamide (1.5%GL-1.5%DMFA), (iii) Cáceres extender supplemented with 1.5% glycerol and 2.5% dimethylformamide (1.5%GL-2.5%DMFA) and (iv) Cáceres extender supplemented with 4% dimethylformamide (4%DMFA). After at least 4 weeks of storage in liquid nitrogen (LN), straws were thawed and semen analysed by computer-assisted sperm analysis and flow cytometry (membrane lipid architecture (Merocyanine 540), integrity and sublethal damage (YoPro-1) and mitochondrial membrane potential (JC-1)). After thawing, better results were observed in samples frozen in 4%DMFA or in combinations of 1.5%GL-2.5%DMFA, in fact total motility increased by 16% in the 4%DMFA group compared to 2.5%GL (P DFMA had a lower percentage of mitochondria with lower membrane potential. It is concluded that DMFA improves the outcome of cryopreservation of stallion spermatozoa mainly reducing sublethal cryodamage.

  1. Histopathological effect of sub-lethal concentration of aluminum phosphide (phostoxin on Clarias gariepinus juveniles

    Directory of Open Access Journals (Sweden)

    Kayode B. Olurin

    Full Text Available Abtsract: The study evaluated the effect of sub-lethal concentration of phostoxin on Clarias gariepinus juveniles. C. gariepinus juveniles belonging to the same cohort (40.1±1.2g; 18.1±1.1cm from a commercial fish farm were randomly placed ten in each of 15 plastic tanks containing 15 liters of water. They were exposed for 96 hrs to three sub-lethal concentrations (treatments of phostoxin (0.125, 0.250, 0.5mg L-1 and a phostoxin free control. At the end of 96 hrs exposure, they were dissected and the tissues need for histopathology removed and fixed in Bouin's fluid. The gill filament exhibited fusion at the secondary lamella that was progressive with concentration. At the highest concentration of exposure, the secondary lamellae showed marked pyknotic and necrotic changes characterized by epithelia detachment. The hepatic tissue showed mild inflammatory changes at lower concentrations while at the highest concentration of exposure there was marked inflammation with observed hydropic degeneration. In the kidney, an inflammatory change was only observed in the interstices at the highest dose of exposure with the convoluted tubules showing partial shrinkage. Phostoxin showed to have significantly caused alterations in cyto-architecture of the gills and to a considerable extent liver and kidney of C. gariepinus.

  2. Sublethal toxicity of carbofuran on the African catfish Clarias gariepinus: Hormonal, enzymatic and antioxidant responses.

    Science.gov (United States)

    Ibrahim, Ahmed Th A; Harabawy, Ahmed S A

    2014-08-01

    The present study examined the impacts of carbofuran on endocrinology of the catfish, Clarias gariepinus, for the first time and evaluated cortisol (CRT), triiodothyronine (T3), thyroxin (T4), 17β-estradiol (E2) and testosterone (TST) and the oxidative stress markers including SOD, CAT, GSTs, GSH. The toxic effects on the metabolic enzymes, G6PDH and LDH, in addition to lipid peroxidation (LPO) and DNA damage as biomarkers in Nile catfish, to sublethal exposures of carbofuran (0.16 and 0.49mg/L, for 35 days) were studied. Statistically significant differences between selected parameters between control and carbofuran-treated fish were recorded. Carbofuran caused a significant (p0.05) in gonads of treated fish. The two metabolic enzymes G6PDH and LDH in all tissues exhibited significant decreases (pgariepinus to sublethal doses of carbofuran and allow us to consider catfish as a good bioindicator to reflect the endocrine disrupting impacts of carbofuran, and reflect the potential of this pesticide to cause disturbance in antioxidant defense system as well as metabolism and induction of lipid peroxidation (LPO) and DNA damage in contaminated ecosystems.

  3. Gene expression in Listeria monocytogenes exposed to sublethal concentration of benzalkonium chloride.

    Science.gov (United States)

    Tamburro, Manuela; Ripabelli, Giancarlo; Vitullo, Monia; Dallman, Timothy James; Pontello, Mirella; Amar, Corinne Francoise Laurence; Sammarco, Michela Lucia

    2015-06-01

    In this study, tolerance at sublethal concentration of benzalkonium chloride and transcription levels of mdrL, ladR, lde, sigB and bcrABC genes in Listeria monocytogenes strains were evaluated. Viable cells reduction occurred in 45% of strains and clinical isolates showed lower sensitivity than isolates from foods. An increased transcription of an efflux system encoding gene was found in 60% of strains, and simultaneous mdrL overexpression and ladR underexpression occurred in 30% of isolates. A significant association between reduced benzalkonium chloride activity and both mdrL and sigB overexpression was observed; sigB expression also correlated with both mdrL and ladR genes. The bcrABC gene was only found in six strains, all isolated from foods and sensitive to benzalkonium chloride, and in four strains an underexpression was observed. Disinfection at sublethal concentration was less effective in clinical isolates, and mdrL and sigB expression was significantly affected by disinfection. Further insights are needed to understand the adaptation to benzalkonium chloride and to evaluate whether changes in gene expression could affect the L. monocytogenes virulence traits and persistence in the environment.

  4. Effects of Sublethal Concentrations of Insecticides on the Functional Response of Two Mirid Generalist Predators.

    Directory of Open Access Journals (Sweden)

    Angeliki F Martinou

    Full Text Available The use of agrochemicals particularly pesticides, can hamper the effectiveness of natural enemies, causing disruption in the ecosystem service of biological control. In the current study, the effects of the insecticides thiacloprid and chlorantraniliprole on the functional response curves were assessed for two mirid predator nymphs, Macrolophus pygmaeus Rambur and Nesidiocoris tenuis Reuter. In the absence of insecticides, both predators exhibited a type II functional response when feeding on eggs of the moth Ephestia kuehniella. N. tenuis seems to be a more efficient predator than M. pygmaeus, as model estimated handling time was significantly lower for the former than for the latter. Residual exposure of M. pygmaeus to sublethal concentrations of either insecticide was associated with a change in the asymptote but not the type of the functional response curve. Thiacloprid seems to be the least compatible with M. pygmaeus, as it led to both a significant reduction of the attack rate and an increase in handling time. In contrast, chlorantraniliprole exposure significantly increased the handling time, but not the attack rate of the predator. Residual exposure of N. tenuis to sublethal concentrations of either insecticide did not have a significant effect on the type nor the parameters of the functional response model. The results show that pesticide residues that do not have lethal effects on beneficial arthropods can reduce prey consumption depending on predator species and on likely risks associated with toxicity.

  5. Enhancement of committed hematopoietic stem cell colony formation by nandrolone decanoate after sublethal whole body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Gallicchio, V.S.; Chen, M.G.; Watts, T.D.

    1984-11-01

    The ability of an anabolic steroid, nandrolone decanoate, to increase committed topoietic stem cell (CFU-gm, CFU-e, and BFU-e) colony formation after sublethal irradiation was evaluated. Immediately after receiving whole body irradiation and on the next two days, each mouse was injected intraperitoneally with nandrolone decanoate (1.25 mg) in propylene glycol. Irradiated control mice received only propylene glycol. Compared to controls, drug-treated mice showed marked peripheral blood leukocytosis and more stable packed red cell volume. Drug-treated mice also demonstrated increased erythropoiesis, as CFU-e/BFU-e concentrations from both marrow (9% to 581%) and spleen (15% to 797%) were elevated. Granulopoiesis was increased similarly, as CFU-gm concentrations from marrow (38% to 685%) and spleen (9% to 373%) were elevated. These results demonstrate that nandrolone decanoate enhances hematopoietic stem cell recovery after sublethal whole body irradiation. This suggests that following hematopoietic suppression, nandrolone decanoate may stimulate the recovery of hematopoiesis at the stem cell level and in peripheral blood.

  6. Sublethal effects of fenazaquin on life table parameters of the predatory mite Amblyseius swirskii (Acari: Phytoseiidae).

    Science.gov (United States)

    Alinejad, Marzieh; Kheradmand, Katayoon; Fathipour, Yaghoub

    2014-11-01

    Knowledge of the impact of acaricides on predatory mites is crucial for integrated pest management programs. The present study evaluated the sublethal effect of fenazaquin (Pride(®) 20 % SC, Behavar, Iran) on life table parameters of the subsequent generation of the predatory mite, Amblyseius swirskii Athias-Henriot (Acari: Phytoseiidae), fed on Tetranychus urticae Koch under laboratory conditions [26 ± 1 °C, 70 ± 3 % RH and 16:8 (L:D) h]. The sublethal concentrations including LC10, LC20 and LC30 were determined using a dose-effect assay. The total development time of both sexes enhanced with an increase in concentration. The oviposition period and total fecundity decreased in dose-dependent manner. The intrinsic rate of increase (r) and finite rate of increase (λ) significantly descended with concentration enhancing from LC10 to LC30, compared with the control. The net reproductive rate (R 0) ranged between 2.76 and 7.37 offspring. Overall, the results indicated that fenazaquin had negative effects on development and life table parameters of the subsequent generation of A. swirskii. In conclusion, fenazaquin is not a compatible acaricide with A. swirskii and should not be used with this predatory mite in integrated management of T. urticae.

  7. Sublethal toxicity of nano-titanium dioxide and carbon nanotubes in a sediment dwelling marine polychaete

    Energy Technology Data Exchange (ETDEWEB)

    Galloway, Tamara, E-mail: t.s.galloway@exeter.ac.u [School of Biosciences, Hatherly Laboratories, University of Exeter, EX4 4PS, Exeter, Devon (United Kingdom); Lewis, Ceri [School of Biosciences, Hatherly Laboratories, University of Exeter, EX4 4PS, Exeter, Devon (United Kingdom); Dolciotti, Ida [Universita Politecnica delle Marche, Institute of Biology and Genetics, Via Ranieri, Monte Dago, 60121 Ancona (Italy); Johnston, Blair D. [School of Biosciences, Hatherly Laboratories, University of Exeter, EX4 4PS, Exeter, Devon (United Kingdom); Moger, Julian [School of Physics, Stocker Road, University of Exeter, Devon EX4 4QL (United Kingdom); Regoli, Francesco [Universita Politecnica delle Marche, Institute of Biology and Genetics, Via Ranieri, Monte Dago, 60121 Ancona (Italy)

    2010-05-15

    The ecotoxicology of manufactured nanoparticles (MNPs) in estuarine environments is not well understood. Here we explore the hypothesis that nanoTiO{sub 2} and single walled nanotubes (SWNT) cause sublethal impacts to the infaunal species Arenicola marina (lugworm) exposed through natural sediments. Using a 10 day OECD/ASTM 1990 acute toxicity test, no significant effects were seen for SWNT up to 0.03 g/kg and no uptake of SWNTs into tissues was observed. A significant decrease in casting rate (P = 0.018), increase in cellular damage (P = 0.04) and DNA damage in coelomocytes (P = 0.008) was measured for nanoTiO{sub 2}, with a preliminary LOEC of 1 g/kg. Coherent anti-stokes Raman scattering microscopy (CARS) located aggregates of TiO{sub 2} of >200 nm within the lumen of the gut and adhered to the outer epithelium of the worms, although no visible uptake of particles into tissues was detected. - This study explores the hypothesis that nano-TiO{sub 2} and single walled nanotubes (SWNT) can cause sublethal impacts to Arenicola marina exposed through natural sediments.

  8. Burrowing, byssus, and biomarkers: behavioral and physiological indicators of sublethal thermal stress in freshwater mussels (Unionidae)

    Science.gov (United States)

    Archambault, Jennifer M.; Cope, W. Gregory; Kwak, Thomas J.

    2013-01-01

    Recent research has elucidated the acute lethal effects of elevated water temperatures to glochidia (larvae), juvenile, and adult life stages of freshwater mussels (Order Unionida), but few studies have focused on sublethal effects of thermal stress. We evaluated the sublethal effects of elevated temperature on burrowing behavior and byssus production in juveniles, and on enzymatic biomarkers of stress in adults in acute (96 h) laboratory experiments in sediment, with two acclimation temperatures (22 and 27 °C) and two experimental water levels (watered and dewatered) as proxies for flow regime. Increasing temperature significantly reduced burrowing in all five species tested, and the dewatered treatment (a proxy for drought conditions) reduced burrowing in all but Amblema plicata. Production of byssal threads was affected most drastically by flow regime, with the probability of byssus presence reduced by 93–99% in the dewatered treatment, compared to the watered treatment (a proxy for low flow conditions); increasing temperature alone reduced byssus by 18–35%. Alanine aminotransferase and aspartate aminotransferase were significantly affected by treatment temperature in the 27 °C acclimation, watered test (p = 0.04 and 0.02, respectively). Our results are important in the context of climate change, because stream temperature and flow are expected to change with increasing air temperature and altered precipitation patterns.

  9. Growth kinetics of Isochrysis galbana in cultures containing sublethal concentrations of mercuric chloride

    Energy Technology Data Exchange (ETDEWEB)

    Davies, A.G.

    1974-01-01

    Measurements of the effect of mercuric chloride upon the growth of Isochrysis galbana in culture are reported. The mercury was concentrated by the plant cells to a very high level, even sublethal intracellular concentrations being of the order of 1 g/l. It is shown that the specific growth rate of the cells in the presence of mercury was reduced linearly by increasing intracellular levels of the metal, thus providing a convenient relationship between growth and mercury uptake. The intracellular concentration which just prevented growth (about 2 g/l) was not instantly lethal, and the loss of mercury from the cultures due to volatilizaton caused by chemical reduction of the ionic form eventually allowed growth to start again giving final population levels approaching that in the control. The presence of mercury in the cells was found to have a considerable effect upon the mean cell volumes in the cultures causing almost a doubling of size at the highest sublethal concentrations examined; this was probably due to combination of the metal with the sulphur-containing compounds which are known to be of importance in the process of cell division.

  10. Bacterial adaptation to sublethal antibiotic gradients can change the ecological properties of multitrophic microbial communities.

    Science.gov (United States)

    Friman, Ville-Petri; Guzman, Laura Melissa; Reuman, Daniel C; Bell, Thomas

    2015-05-07

    Antibiotics leak constantly into environments due to widespread use in agriculture and human therapy. Although sublethal concentrations are well known to select for antibiotic-resistant bacteria, little is known about how bacterial evolution cascades through food webs, having indirect effect on species not directly affected by antibiotics (e.g. via population dynamics or pleiotropic effects). Here, we used an experimental evolution approach to test how temporal patterns of antibiotic stress, as well as migration within metapopulations, affect the evolution and ecology of microcosms containing one prey bacterium, one phage and two protist predators. We found that environmental variability, autocorrelation and migration had only subtle effects for population and evolutionary dynamics. However, unexpectedly, bacteria evolved greatest fitness increases to both antibiotics and enemies when the sublethal levels of antibiotics were highest, indicating positive pleiotropy. Crucially, bacterial adaptation cascaded through the food web leading to reduced predator-to-prey abundance ratio, lowered predator community diversity and increased instability of populations. Our results show that the presence of natural enemies can modify and even reverse the effects of antibiotics on bacteria, and that antibiotic selection can change the ecological properties of multitrophic microbial communities by having indirect effects on species not directly affected by antibiotics.

  11. Effects of Sublethal Doses of Imidacloprid on Young Adult Honeybee Behaviour

    Science.gov (United States)

    Mengoni Goñalons, Carolina; Farina, Walter Marcelo

    2015-01-01

    Imidacloprid (IMI), a neonicotinoid used for its high selective toxicity to insects, is one of the most commonly used pesticides. However, its effect on beneficial insects such as the honeybee Apis mellifera L is still controversial. As young adult workers perform in-hive duties that are crucial for colony maintenance and survival, we aimed to assess the effect of sublethal IMI doses on honeybee behaviour during this period. Also, because this insecticide acts as a cholinergic-nicotinic agonist and these pathways take part in insect learning and memory processes; we used IMI to assess their role and the changes they suffer along early adulthood. We focused on appetitive behaviours based on the proboscis extension response. Laboratory reared adults of 2 to 10 days of age were exposed to sublethal IMI doses (0.25 or 0.50ng) administered orally or topically prior to behavioural assessment. Modification of gustatory responsiveness and impairment of learning and memory were found as a result of IMI exposure. These outcomes differed depending on age of evaluation, type of exposure and IMI dose, being the youngest bees more sensitive and the highest oral dose more toxic. Altogether, these results imply that IMI administered at levels found in agroecosystems can reduce sensitivity to reward and impair associative learning in young honeybees. Therefore, once a nectar inflow with IMI traces is distributed within the hive, it could impair in-door duties with negative consequences on colony performance. PMID:26488410

  12. Lethal and sublethal effects of four essential oils on the egg parasitoids Trissolcus basalis.

    Science.gov (United States)

    Werdin González, Jorge Omar; Laumann, Raúl Alberto; da Silveira, Samantha; Moraes, Maria Carolina Blassioli; Borges, Miguel; Ferrero, Adriana Alicia

    2013-07-01

    The essential oils from leaves of Schinus molle var. areira, Aloysia citriodora, Origanum vulgare and Thymus vulgaris have showed potential as phytoinsecticides against the green stink bug, Nezara viridula. In this work were evaluated their toxicological and behavioral effects on the parasitoid Trissolcus basalis, a biological control agent of this pest insect. Essential oils were obtained via hydrodestillation from fresh leaves. Insecticide activity in T. basalis females was evaluated in direct contact and fumigation bioassays. Behavioral effects were evaluated in olfactometer bioassays. To evaluate the residual toxicity, females of the parasitoids were exposed to oil residues; in these insects, the sublethal effects were evaluated (potential parasitism and survivorship of immature stages). The essential oils from O. vulgare and T. vulgaris proved to be highly selective when used as fumigant and did not change parasitoid behavior. After one week, the residues of these oils were harmless and did not show sublethal effects against T. basalis. According with these results, essential oils have potential applications for the integrated management of N. viridula.

  13. Gill lesions in the major carp, Labeo rohita exposed to lethal and sublethal concentrations of tannery effluent.

    Science.gov (United States)

    Dhanapakiam, P; Sampoorani, V; Kavitha, M; Ramasamy, V K; Chandrakala, A; Aruna, K C

    2004-07-01

    The major carp, Labeo rohita were exposed to (0.873%) lethal and sublethal (0.073%) concentrations of tannery effluent for 24h and 40 days respectively under static bioassay condition. The surface architecture of gill revealed severe damages such as : fusion and clumping in the middle and distal parts of the primary lamellae, swelling and deterioration of the cells. The interlamellar space was filled either with hyperplastic epithelial or mucous cells. Secondary lamellae lost their identity and appeared finger like in structure in the lethal concentration and necrosis was observed in the primary and secondary epithelium. Swelling of primary and secondary epithelial cells was evident in sublethal concentration.

  14. The sublethal effects of the organochlorines dieldrin and lindane on growth and reproduction of Eudrilus eugeniae and Eisenia fetida (Oligochaeta

    Directory of Open Access Journals (Sweden)

    Editorial Office

    1994-07-01

    Full Text Available Experimental exposure of the earthworm species Eudrilus eugeniae to organochlorines showed that dieldrin causes damage to sperm ultrastructure when viewed electronmicroscopically. Worms containing concentrations of 7,27 mg/kg dieldrin and higher showed more than 10% sperm damage. Exposure of Eisenia fetida to sublethal concentrations of lindane did not result in sperm damage but demonstrated an increase in growth and reproductive activity. It is argued that quantification of sperm damage and correlation with pesticide concentration could provide a useful tool for evaluating environmental quality. Furthermore, the effects of sublethal concentrations of pesticides that manifest themselves in increased growth and reproductive activity could affect ecological balances.

  15. Progress of peripheral nerve repair

    Institute of Scientific and Technical Information of China (English)

    陈峥嵘

    2002-01-01

    Study on repair of peripheral nerve injury has been proceeding over a long period of time. With the use of microsurgery technique since 1960s,the quality of nerve repair has been greatly improved. In the past 40 years, with the continuous increase of surgical repair methods, more progress has been made on the basic research of peripheral nerve repair.

  16. Nuclear apoJ: A low dose radiation inducible regulator of cell death. Final report for period September 15, 1998 - September 14, 2001

    Energy Technology Data Exchange (ETDEWEB)

    Aronow, Bruce J.

    2002-04-19

    we constructed through gene targeting to increasing levels of ionizing radiation from a Cesium source. Data gathered under the support of this grant application initially indicated that apoJ deficient animals were more resistant to radiation, but as we accumulated more and more data points and covered a tighter exposure range, the genotype-based differences became insignificant. However, the possibility existed that because mortality based radiation-resistance could be attributable to mechanism for which nuclear apoJ was not rate determining, we maintained a very large of colony of apoJ knockout and wildtype animals in both the C57/B16 and Cv129 strain backgrounds that were exposed to sub-lethal levels of ionizing radiation to monitor for the occurrence of tumors. These animals were allowed to fully recover and age normally in either germ free or normal animal housing. Our results demonstrated no significant differences between wildtype and apoJ knockout animals over a period that extended up to 30 months for individual animals. We recorded similar weight gain, a relatively low mortality rate, and a similar mixture and rate of sarcoma and adenocarcinomas after surviving the initial ionizing radiation exposures. Thus we conclude that apoJ gene function, which was totally eliminated by our gene targeting, did not influence radiation sensitivity or serve as a tumor suppressor in response to DNA damage.

  17. Achilles tendon repair

    Science.gov (United States)

    Achilles tendon rupture-surgery; Percutaneous Achilles tendon rupture repair ... To fix your torn Achilles tendon, the surgeon will: Make a cut down the back of your heel Make several small cuts rather than one large cut ...

  18. Diaphragmatic hernia repair - slideshow

    Science.gov (United States)

    ... presentations/100014.htm Diaphragmatic hernia repair - series—Normal anatomy To use the sharing ... Overview The chest cavity includes the heart and lungs. The abdominal cavity includes the liver, the stomach, ...

  19. Eye muscle repair - slideshow

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/presentations/100062.htm Eye muscle repair - series—Normal anatomy To use the sharing ... the eyeball to the eye socket. The external muscles of the eye are found behind the conjunctiva. ...

  20. Tracheoesophageal fistula repair - slideshow

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/presentations/100103.htm Tracheoesophageal fistula repair - series—Normal anatomy To use the sharing ... Editorial team. Related MedlinePlus Health Topics Esophagus Disorders Fistulas Tracheal Disorders A.D.A.M., Inc. is ...

  1. Inguinal hernia repair - slideshow

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/presentations/100027.htm Inguinal hernia repair - series—Normal anatomy To use the sharing ... to slide 4 out of 4 Overview A hernia occurs when part of an organ protrudes through ...

  2. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; Nancy Porter; Mike Sullivan; Chris Neary

    2004-04-12

    The two broad categories of deposited weld metal repair and fiber-reinforced composite liner repair technologies were reviewed for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Preliminary test programs were developed for both deposited weld metal repair and for fiber-reinforced composite liner repair. Evaluation trials have been conducted using a modified fiber-reinforced composite liner provided by RolaTube and pipe sections without liners. All pipe section specimens failed in areas of simulated damage. Pipe sections containing fiber-reinforced composite liners failed at pressures marginally greater than the pipe sections without liners. The next step is to evaluate a liner material with a modulus of elasticity approximately 95% of the modulus of elasticity for steel. Preliminary welding parameters were developed for deposited weld metal repair in preparation of the receipt of Pacific Gas & Electric's internal pipeline welding repair system (that was designed specifically for 559 mm (22 in.) diameter pipe) and the receipt of 559 mm (22 in.) pipe sections from Panhandle Eastern. The next steps are to transfer welding parameters to the PG&E system and to pressure test repaired pipe sections to failure. A survey of pipeline operators was conducted to better understand the needs and performance requirements of the natural gas transmission industry regarding internal repair. Completed surveys contained the following principal conclusions: (1) Use of internal weld repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway crossings. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling (HDD) when a new bore must be created

  3. Pectus excavatum repair - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100035.htm Pectus excavatum repair - series—Normal anatomy To use the sharing ... Go to slide 4 out of 4 Overview Pectus excavatum is a deformity of the front of the ...

  4. Hiatal hernia repair - slideshow

    Science.gov (United States)

    ... presentations/100028.htm Hiatal hernia repair - series—Normal anatomy To use the sharing features on ... Overview The esophagus runs through the diaphragm to the stomach. It functions to carry food from the mouth ...

  5. Repairing ceramic insulating tiles

    Science.gov (United States)

    Dunn, B. R.; Laymance, E. L.

    1980-01-01

    Fused-silica tiles containing large voids or gauges are repaired without adhesives by plug insertion method. Tiles are useful in conduits for high-temperature gases, in furnaces, and in other applications involving heat insulation.

  6. Rotator cuff repair - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100229.htm Rotator cuff repair - series—Normal anatomy To use the sharing ... to slide 4 out of 4 Overview The rotator cuff is a group of muscles and tendons that ...

  7. Cleft lip repair - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100010.htm Cleft lip repair - series—Normal anatomy To use the sharing ... abnormal opening in the middle of the upper lip. A cleft palate is an opening in the roof of ...

  8. How to Relate Complex DNA Repair Genotypes to Pathway Function and, Ultimately, Health Risk

    Energy Technology Data Exchange (ETDEWEB)

    Jones, IM

    2002-01-09

    Exposure to ionizing radiation increases the incidence of cancer. However, predicting which individuals are at most risk from radiation exposure is a distant goal. Predictive ability is needed to guide policies that regulate radiation exposure and ensure that medical treatments have maximum benefit and minimum risk. Differences between people in susceptibility to radiation are largely based on their genotype, the genes inherited from their parents. Among the important genes are those that produce proteins that repair DNA damaged by radiation. Base Excision Repair (BER) proteins repair single strand breaks and oxidized bases in DNA. Double Strand Break Repair proteins repair broken chromosomes. Using technologies and information from the Human Genome Project, we have previously determined that the DNA sequence of DNA repair genes varies within the human population. An average of 3-4 different variants were found that affect the protein for each of 37 genes studied. The average frequency of these variants is 5%. Given the many genes in each DNA repair pathway and their many variants, technical ability to determine an individual's repair genotype greatly exceeds ability to interpret the information. A long-term goal is to relate DNA repair genotypes to health risk from radiation. This study focused on the BER pathway. The BER genes are known, variants of the genes have been identified at LLNL, and LLNL had recently developed an assay for BER function using white blood cells. The goal of this initial effort was to begin developing data that could be used to test the hypothesis that many different genotypes have similar DNA repair capacity phenotypes (function). Relationships between genotype and phenotype could then be used to group genotypes with similar function and ultimately test the association of groups of genotypes with health risk from radiation. Genotypes with reduced repair function are expected to increase risk of radiation-induced health effects. The

  9. Grey Repairable System Analysis

    Institute of Scientific and Technical Information of China (English)

    Renkuan Guo; Charles Ernie Love

    2006-01-01

    In this paper, we systematically discuss the basic concepts of grey theory, particularly the grey differential equation and its mathematical foundation, which is essentially unknown in the reliability engineering community. Accordingly,we propose a small-sample based approach to estimate repair improvement effects by partitioning system stopping times into intrinsic functioning times and repair improvement times. An industrial data set is used for illustrative purposes in a stepwise manner.

  10. Do high temperatures enhance the negative effects of ultraviolet-B radiation in embryonic and larval amphibians?

    Directory of Open Access Journals (Sweden)

    Lesley A. Alton

    2012-07-01

    For the embryos and tadpoles of amphibian species, exposure to ultraviolet-B radiation (UVBR can be lethal, or cause a variety of sublethal effects. Low temperatures enhance the detrimental effects of UVBR and this is most likely because the enzyme-mediated processes involved in the repair of UVBR-induced damage function less effectively at low temperatures. Whether these repair processes are also impaired, and thus the negative effects of UVBR similarly enhanced, at high temperatures is not known, but is an ecologically relevant question to ask given that organisms that inhabit environments where the temperature fluctuates widely on a daily timescale are likely to experience high doses of UVBR when temperatures are high. Here we examined the thermal-dependence of UVBR effects in the context of an ecologically-relevant fluctuating UVBR and temperature regime to test the hypothesis that exposure to peak UVBR levels while the temperature is high (35°C is more detrimental to embryonic and larval Limnodynastes peronii than exposure to peak UVBR levels while the temperature is moderate (25°C. Embryos exposed to peak UVBR levels at 35°C hatched 10 h later than those exposed to peak UVBR levels at 25°C and, as tadpoles, were smaller and consequently swam more slowly but, in an environment with predators, exhibited no difference in survival time. There was also no effect of experimental treatment on the hatching success of embryos, nor on the post-hatch survival of tadpoles. These findings, therefore, are not sufficiently strong to support our hypothesis that high temperatures enhance the negative effects of UVBR in embryonic and larval amphibians.

  11. Sublethal transient global ischemia stimulates migration of neuroblasts and neurogenesis in mice.

    Science.gov (United States)

    Li, Ying; Yu, Shan Ping; Mohamad, Osama; Genetta, Thomas; Wei, Ling

    2010-09-01

    Increasing evidence has shown the potential of neuronal plasticity in adult brain after injury. Neural proliferation can be triggered by a focal sublethal ischemic preconditioning event; whether mild global ischemia could cause neurogenesis has been not clear. The present study investigated stimulating effects of sublethal transient global ischemia (TGI) on endogenous neurogenesis and neuroblast migration in the subventricular zone (SVZ), dentate gyrus, and peri-infarct areas of the adult cortex. Adult mice of 129S2/Sv strain were subjected to 8-min bilateral common carotid artery ligation followed by 5-bromo-2'-deoxyuridine (BrdU; 50 mg/kg, intraperitoneal) administration every day until being sacrificed at 1-21 days after reperfusion. The mild TGI did not induce neuronal cell death for up to 7 days after TGI, as evidenced by negative terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining among NeuN-positive cells in the hippocampus and neocortex. In TGI animals, BrdU staining revealed enhanced proliferation of neuroblasts and their migration track from the SVZ into the striatum and neocortex. In the corpus callosum, there were more BrdU-positive cells in the TGI group in the first 2 days. Increasing numbers of BrdU-positive cells were seen 7-21 days later in the striatum and cortex of TGI mice. The cortex of TGI animals showed increased expression of erythropoietin, erythropoietin receptor, fibroblast growth factor 2, vascular endothelial growth factor, and phosphorylated Jun N-terminal kinase; the expression was peaked 2 to 3 days after reperfusion. BrdU and NeuN double staining in the dentate gyrus, striatum, and cortex implied increased neurogenesis induced by the TGI preconditioning. Doublecortin (DCX)-positive cells increased in the cortex of TGI mice, localized to cortical layers II, III, and V, and many stained positive for the mature neuronal markers NeuN, neurofilament, N-methyl-d-aspartic acid receptor subunit gene NR1, or the

  12. Toxicity, sublethal effects, and potential modes of action of select fungicides on freshwater fish and invertebrates

    Science.gov (United States)

    Elskus, Adria A.

    2012-01-01

    Despite decades of agricultural and urban use of fungicides and widespread detection of these pesticides in surface waters, relatively few data are available on the effects of fungicides on fish and invertebrates in the aquatic environment. Nine fungicides are reviewed in this report: azoxystrobin, boscalid, chlorothalonil, fludioxonil, myclobutanil, fenarimol, pyraclostrobin, pyrimethanil, and zoxamide. These fungicides were identified as emerging chemicals of concern because of their high or increasing global use rates, detection frequency in surface waters, or likely persistence in the environment. A review of the literature revealed significant sublethal effects of fungicides on fish, aquatic invertebrates, and ecosystems, including zooplankton and fish reproduction, fish immune function, zooplankton community composition, metabolic enzymes, and ecosystem processes, such as leaf decomposition in streams, among other biological effects. Some of these effects can occur at fungicide concentrations well below single-species acute lethality values (48- or 96-hour concentration that effects a response in 50 percent of the organisms, that is, effective concentration killing 50 percent of the organisms in 48 or 96 hours) and chronic sublethal values (for example, 21-day no observed adverse effects concentration), indicating that single-species toxicity values may dramatically underestimate the toxic potency of some fungicides. Fungicide modes of toxic action in fungi can sometimes reflect the biochemical and (or) physiological effects of fungicides observed in vertebrates and invertebrates; however, far more studies are needed to explore the potential to predict effects in nontarget organisms based on specific fungicide modes of toxic action. Fungicides can also have additive and (or) synergistic effects when used with other fungicides and insecticides, highlighting the need to study pesticide mixtures that occur in surface waters. For fungicides that partition to

  13. Relative potency of PCB126 to TCDD for sublethal embryotoxicity in the mummichog (Fundulus heteroclitus).

    Science.gov (United States)

    Rigaud, Cyril; Couillard, Catherine M; Pellerin, Jocelyne; Légaré, Benoît; Gonzalez, Patrice; Hodson, Peter V

    2013-03-15

    The relative potency (ReP) of 3,3',4,4',5-pentachlorobiphenyl (PCB126) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for sublethal responses was assessed in Fundulus heteroclitus embryos. Eggs were treated with intravitelline injections of graded sublethal doses of PCB126 (312-5000 pg g(-1) wet weight, ww) or TCDD (5-1280 pg g(-1) ww). At 16 days post-fertilization (DPF), craniofacial deformities were observed in larvae hatched from eggs treated with the two highest doses of PCB126 (2500-5000 pg g(-1) ww). Both compounds caused a dose-responsive reduction of larval growth and prey capture ability (at ≥1250 pg g(-1) ww), and induction of ethoxyresorufin-O-deethylase (EROD) activity (at ≥80 pg g(-1) ww). The dose-response relationships for EROD activity for PCB126 and TCDD had similar slopes and the ReP of PCB126 to TCDD for EROD activity was estimated at 0.71. This is 140-fold higher than the World Health Organization (WHO) TCDD equivalency factor (TEF) of PCB126 for fish (0.005), which is based on rainbow trout (Oncorhynchus mykiss) embryolethality data. The slope of the dose-response relationship for prey capture ability for PCB126 was steeper than for TCDD, suggesting different mechanisms of action. Expression levels of several genes were also studied by quantitative real-time polymerase chain reaction (qPCR) following exposure to single doses of TCDD or PCB126 (1280 and 1250 pg g(-1) ww, respectively) causing similar EROD induction. A different pattern of responses was observed between PCB126 and TCDD: PCB126 appeared to induce antioxidant responses by inducing sod2 expression, while TCDD did not. These results suggest that relative potencies are species-specific and that the current ReP for PCB126 underestimates its toxicity for some fish species. It is recommended to develop species-specific RePs for a variety of sublethal endpoints and at environmentally relevant doses.

  14. Transmission electron microscopy study of Listeria monocytogenes serotype 1/2a cells exposed to sublethal heat stress and carvacrol

    Science.gov (United States)

    The objective of this study was to investigate the morphological changes that occurred in Listeria monocytogenes serotype 1/2a cells as visualized by transmission electron microscopy (TEM) after exposure to sublethal heat stress at 48°C for 60 min and in combination with lethal concentration of carv...

  15. A comparison of the sublethal and lethal toxicity of four pesticides in Hyalella azteca and Chironomus dilutus.

    Science.gov (United States)

    Hasenbein, Simone; Connon, Richard E; Lawler, Sharon P; Geist, Juergen

    2015-08-01

    Laboratory toxicity testing is the primary tool used for surface water environmental risk assessment; however, there are critical information gaps regarding the sublethal effects of pesticides. In 10-day exposures, we assessed the lethal and sublethal (motility and growth) toxicities of four commonly used pesticides, bifenthrin, permethrin, cyfluthrin, and chlorpyrifos, on two freshwater invertebrates, Chironomus dilutus and Hyalella azteca. Pyrethroids were more toxic than the organophosphate chlorpyrifos in both species. Bifenthrin was most toxic to H. azteca survival and growth. Cyfluthrin was most toxic to C. dilutus. However, cyfluthrin had the greatest effect on motility on both H. azteca and C. dilutus. The evaluated concentrations of chlorpyrifos did not affect C. dilutus motility or growth, but significantly impacted H. azteca growth. Motility served as the most sensitive endpoint in assessing sublethal effects at low concentrations for both species, while growth was a good indicator of toxicity for all four pesticides for H. azteca. The integration of sublethal endpoints in ambient water monitoring and pesticide regulation efforts could improve identification of low-level pesticide concentrations that may eventually cause negative effects on food webs and community structure in aquatic environments.

  16. Sub-lethal effects of Vip3A toxin on survival, development and fecundity of Heliothis virescens and Plutella xylostella.

    Science.gov (United States)

    Gulzar, Asim; Wright, Denis J

    2015-11-01

    The assessment of sub-lethal effects is important to interpret the overall insecticide efficacy in controlling insect pest populations. In addition to the lethal effect, sub-lethal effects may also occur in exposed insects. Vegetative insecticidal proteins (Vips) have shown a broad spectrum of insecticidal activity against many insect pest species. In this study the sub-lethal effects of the Bacillus thuringiensis vegetative insecticidal toxin Vip3A on the development and reproduction of Heliothis virescens F. and Plutella xylostella L. were evaluated in the laboratory. The results indicated that the sub-lethal concentration of Vip3A increased the duration of the larval and pupal stages as compared with the control treatment for both species. The percent pupation and percent adult emergence were significantly lower for Vip3A-treated insects. The proportion of pairs that produced eggs and the longevity of adults were not significantly different between treatments. H. virescens and P. xylostella treated with Vip3A showed an 11 and 17 % decrease in their intrinsic rate of increase (rm) respectively compared with untreated insects. The results from this study will be helpful to develop the strategy to incorporate Vip 3A containing crops in an integrated pest management programme.

  17. Lethal and sublethal effects of the chitin synthesis inhibitor chlorfluazuron on Bradysia odoriphaga Yang and Zhang (Diptera: Sciaridae).

    Science.gov (United States)

    Zhang, Peng; Zhao, Yun-He; Wang, Qiu-Hong; Mu, Wei; Liu, Feng

    2017-03-01

    Bradysia odoriphaga Yang and Zhang is the primary insect pest that affects Chinese chive in northern China. Nevertheless, very few studies have been conducted on the use of chitin synthesis inhibitors (CSIs) for the control of B. odoriphaga. Here, lethal and sublethal effects of the CSI chlorfluazuron on B. odoriphaga were studied to explore the use for integrated pest management (IPM) of B. odoriphaga. A contact and ingestion toxicity bioassay showed that chlorfluazuron was more active against B. odoriphaga than three other CSIs, with a 72h LC50 of 0.1593mg/L. Treatment with the LC50 dose of chlorfluazuron decreased both the intrinsic and finite rates of increase of B. odoriphaga, in addition to reproduction rate, survival rate, and fecundity, and the mean generation time, total preovipositional period and larval development duration were shortened, compared with those of the control and LC10 groups. The mean generation time, total preovipositional period and larval development duration were all also markedly decreased by treatment with chlorfluazuron at the LC10. Furthermore, chlorfluazuron inhibited the feeding of the final instar larvae for a short period. Glutathione S-transferase and microsomal mixed function oxidase activities increased after exposure to the chemical. These results showed that chlorfluazuron at the sublethal LC50 treatment inhibited B. odoriphaga population growth, whereas the danger of causing rapid population growth by using a lower sublethal concentration was demonstrated with the sublethal LC10 treatment. Therefore, chlorfluazuron should be used with caution in an IPM program for B. odoriphaga.

  18. Low, medium and high heat tolerant strains of Listeria monocytogenes and increased heat stress resistance after exposure to sublethal heat

    Science.gov (United States)

    Listeria monocytogenes exhibits sophisticated adaptive mechanisms to counteract higher levels of lethal acid, heat, salt or oxidative stresses after pre-exposure to sublethal concentrations of homogenous stress. A group of 37 strains representing all 13 serotypes of Listeria monocytogenes with initi...

  19. Sublethal effects of Imidacloprid on honey bee colony growth and activity at three sites in the U.S.

    Science.gov (United States)

    Field experiments in southern Arizona, central Arkansas and southern Mississippi were conducted to evaluate the effects of sublethal concentrations (0, 5, 20 and 100 ppb) of imidacloprid in sugar syrup on honey bee colony growth and activity. Response variables included discrete data from hive inspe...

  20. Toxicity and sub-lethal effect of endemic plants from family Anacardiaceae on oviposition behavior of Aedes albopictus

    Directory of Open Access Journals (Sweden)

    Wan Fatma Zuharah

    2015-08-01

    Conclusions: These results clearly indicate that the acetone extract of G. renghas could be served as potential larvicide, whereas M. fasciculiflora has better sub-lethal effect for oviposition deterrence and against Ae. albopictus as an oviciding agent.

  1. Lethal and sub-lethal effects of five pesticides used in rice farming on the earthworm Eisenia fetida

    NARCIS (Netherlands)

    Rico, Andreu; Sabater, Consuelo; Castillo, María Ángeles

    2016-01-01

    The toxicity of five pesticides typically used in rice farming (trichlorfon, dimethoate, carbendazim, tebuconazole and prochloraz) was evaluated on different lethal and sub-lethal endpoints of the earthworm Eisenia fetida. The evaluated endpoints included: avoidance behaviour after an exposure pe

  2. Uptake and elimination of 1,2,4-trichlorobenzene in the guppy (Poecilia reticulata) at sublethal and lethal aqueous concentrations.

    NARCIS (Netherlands)

    Eck, van J.M.C.; Koelmans, A.A.; Deneer, J.W.

    1997-01-01

    The kinetics of 1,2,4-trichlorobenzene in guppies (Poecilia reticulata) have been studied in an accumulation and elimination experiment. At a sublethal exposure, uptake and elimination rate constants of 1,2,4-trichlorobenzene were determined, employing a first-order one-compartment model. The consta

  3. Lethal and sub-lethal responses of native freshwater mussels exposed to granular Bayluscide®, a sea lamprey larvicide

    Science.gov (United States)

    Newton, Teresa; Boogaard, Michael A.; Gray, Brian R.; Hubert, Terrance D.; Schloesser, Nicholas

    2017-01-01

    The invasive sea lamprey (Petromyzon marinus) poses a substantial threat to fish communities in the Great Lakes. Efforts to control sea lamprey populations typically involve treating tributary streams with lampricides on a recurring cycle. The presence of a substantial population of larval sea lampreys in the aquatic corridor between Lakes Huron and Erie prompted managers to propose a treatment using the granular formulation of Bayluscide® that targets larval sea lampreys that reside in sediments. However, these treatments could cause adverse effects on native freshwater mussels—imperiled animals that also reside in sediments. We estimated the risk of mortality and sub-lethal effects among eight species of adult and sub-adult mussels exposed to Bayluscide® for durations up to 8 h to mimic field applications. Mortality was appreciable in some species, especially in sub-adults (range, 23–51%). The lethal and sub-lethal effects were positively associated with the duration of exposure in most species and life stage combinations. Estimates of the median time of exposure that resulted in lethal and sub-lethal effects suggest that sub-adults were often affected by Bayluscide® earlier than adults. Siphoning activity and burrowing position of mussels during exposure may have moderated the uptake of Bayluscide® and may have influenced lethal and sub-lethal responses. Given that the various species and life stages were differentially affected, it will be difficult to predict the effects of Bayluscide® treatments on mussels.

  4. DNA repair, immunosuppression, and skin cancer.

    Science.gov (United States)

    Yarosh, Daniel B

    2004-11-01

    UV radiation (UVR) produces erythema within the first 24 hours of exposure, suppression of the immune system within the first 10 days, and, for many people, over the course of decades, skin cancer. Although UVR damages many skin targets, DNA damage in the form of cyclobutane pyrimidine dimers (CPDs) is an important mediator of these sequelae. The action spectrum for erythema parallels the action spectrum for CPD formation in skin, and in the absence of repair, as in the genetic disease xeroderma pigmentosum (XP), skin cancer rates are dramatically increased. DNA repair in skin can be enhanced by the delivery of DNA repair enzymes encapsulated in liposomes. Used in this way, photoreactivation of CPDs greatly diminishes erythema and the suppression of contact hypersensitivity (CHS). UV endonucleases delivered by liposomes also prevent UV-induced suppression of delayed-type hypersensitivity. In a clinical study of patients with XP, T4 endonuclease V (T4N5) liposome lotion applied for one year reduced the rates of actinic keratosis (AK) and skin cancer compared with placebo. These results showed that strategies to increase sun protection should include measures to reduce DNA damage and increase the rate of DNA repair.

  5. Repair technology for steam generator tubes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seung Ho; Jung, Hyun Kyu; Jung, Seung Ho; Kim, Chang Hoi; Jung, Young Moo; Seo, Yong Chil; Kim, Jung Su; Seo, Moo Hong

    2001-02-01

    The most commonly used sleeving materials are thermally treated Alloy 600 and thermally treated Alloy 690 Alloy. Currently, thermally treated Alloy 690 and Alloy 800 are being offered although Alloy 800 has not been licensed in the US. To install sleeve, joint strength, leak tightness, PWSCC resistance, evaluation on process parameter range and the effect of equipments and procedures on repair plan and radiation damage have to be investigated before sleeving. ABB CE provides three type of leak tight Alloy 690 TIG welded and PLUSS sleeve. Currently, Direct Tube Repair technique using Nd:YAG laser has been developed by ABB CE and Westinghouse. FTI has brazed and kinetic sleeve designs for recirculating steam generator and hydraulic and rolled sleeve designs for one-through steam generators. Westinghouse provides HEJ, brazed and laser welded sleeve design. When sleeve is installed in order to repair the damaged S/G tubes, it is certain that defects can be occurred due to the plastic induced stress and thermal stress. Therefore it is important to minimize the residual stress. FTI provides the electrosleeve technique as a future repair candidate using electroplating.

  6. Influence of sublethal concentrations of common disinfectants on expression of virulence genes in Listeria monocytogenes

    DEFF Research Database (Denmark)

    Kastbjerg, Vicky Gaedt; Larsen, M. H.; Gram, Lone

    2010-01-01

    Listeria monocytogenes is a food-borne human pathogen that causes listeriosis, a relatively rare infection with a high fatality rate. The regulation of virulence gene expression is influenced by several environmental factors, and the aim of the present study was to determine how disinfectants used...... routinely in the food industry affect the expression of different virulence genes in L. monocytogenes when added at sublethal concentrations. An agar-based assay was developed to screen the effect of disinfectants on virulence gene promoter expression and was validated at the transcriptional level...... by Northern blot analysis. Eleven disinfectants representing four different groups of active components were evaluated in this study. Disinfectants with the same active ingredients had a similar effect on gene expression. Peroxy and chlorine compounds reduced the expression of the virulence genes...

  7. Sublethal effects of the antibiotic tylosin on estuarine benthic microalgal communities.

    Science.gov (United States)

    Pinckney, James L; Hagenbuch, Isaac M; Long, Richard A; Lovell, Charles R

    2013-03-15

    Pharmaceuticals are common chemical contaminants in estuaries receiving effluent from wastewater and sewage treatment facilities. The purpose of this research was to examine benthic microalgal (BMA) community responses to sublethal exposures to tylosin, a common and environmentally persistent antibiotic. Bioassays, using concentrations of 0.011-218 μmol tylosin l(-1), were performed on intertidal muddy sediments from North Inlet Estuary, SC. Exposure to tylosin resulted in a reduction in total BMA biomass and primary productivity. Furthermore, exposure seemed to retard diatom growth while having a minimal effect on cyanobacteria biomass. Estuarine systems receiving chronic inputs of trace concentrations of tylosin, as well as other antibiotics, may experience significant reductions in BMA biomass and primary productivity. Given the well-documented role of BMA in the trophodynamics of estuaries, these impacts will likely be manifested in higher trophic levels with possible impairments of the structure and function of these sensitive systems. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Model study on the clinical signs and residue concentrations of sublethal carbofuran poisoning in birds.

    Science.gov (United States)

    Lehel, J; Laczay, P; Déri, J; Darin, E G; Budai, P

    2010-10-01

    The incidence of fatal poisoning of birds of prey caused by carbofuran has increased markedly in Hungary since 2007. An experimental model with broiler chickens was used to study clinical signs of sublethal carbofuran poisoning in birds and to measure the residue concentrations of carbamate in tissues after exposure. Eight chickens were treated with a carbofuran-containing insecticide orally by gastric tube at a single dose of 2.5 mg/kg body weight, and clinical signs of poisoning were observed. Gas chromatography was used to determine carbofuran concentrations in the blood, muscle, and liver samples, and in stomach contents. Poisoning was characterized by typical muscarinic and nicotinic clinical signs without mortality. Carbofuran in the stomach and edible tissues of acutely poisoned birds may lead to secondary poisoning of predators and may also present risks to human health.

  9. Immunologic parameters evaluations in Nile tilapia (Oreochromis niloticus) exposed to sublethal concentrations of diazinon.

    Science.gov (United States)

    Girón-Pérez, M I; Velázquez-Fernández, J; Díaz-Resendiz, K; Díaz-Salas, F; Canto-Montero, C; Medina-Díaz, I; Robledo-Marenco, M; Rojas-García, A; Zaitseva, G

    2009-08-01

    Fish resistance to microorganisms depends basically on the immune response. Although there are several studies on the diazinon mammalian immunotoxicity, in the case of fish there are only few. The aim of present study was to evaluate the effect of diazinon on immunological parameters (relative spleen weight, splenocytes count, lysozyme activity, respiratory burst and IgM concentration) in Nile tilapia. Diazinon at sublethal concentrations (0.39 and 0.78 mg/L) did not alter RSW, splenocytes count or lysozyme activity. However, at the highest concentration tested (1.96 mg/L) diazinon significantly increased respiratory burst and IgM concentration. In summary, diazinon (and perhaps other pesticides) could alter immunological response and induce oxidative stress.

  10. PAH-induced sublethal narcosis alters the bioenergetics and bioaccumulation of Fundulus heteroclitus

    Energy Technology Data Exchange (ETDEWEB)

    Merten, A. [NOAA Office of Response and Restoration, Hazardous Materials and Response, Seattle (United States); Beard, E.; Baker, B. [Univ. of Maryland, Solomons (United States)

    2004-09-15

    Accumulation of non-polar narcotic chemicals in organisms alters their metabolic rates and, therefore their energetic demands. Since exposure of these hydrophobic chemicals is primarily through the diet, we hypothesize that decreasing metabolic rates caused by accumulation of narcotics reduces feeding which, in turn, decreases further exposure to the narcotic. Thus, dietary exposure to and accumulation of narcotics may cause a negative feedback, reducing net bioaccumulation. The purpose of this short paper is to discuss the results of a long-term fish contaminant exposure study and to describe a fish bioenergetics model coupled to a PCBbioaccumulation model. The laboratory component consisted of exposing the estuarine fish Fundulus heteroclitus to environmentally-relevant levels of hydrophobic organic contaminants (HOCs) through their diet. We developed the model to further examine and understand the consequences of sublethal narcosis at both the individual and population levels of Fundulus heteroclitus.

  11. Interactions between Entomopathogenic Fungus, Metarhizium Anisopliae and Sublethal Doses of Spinosad for Control of House Fly, Musca Domestica

    Directory of Open Access Journals (Sweden)

    M Sharififard

    2011-06-01

    Full Text Available Background: Metarhizium anisopliae strain IRAN 437C is one of the most virulent fungal isolates against house fly, Musca domestica. The objective of this study was to determine the interaction of this isolate with sublethal doses of spino­sad against housefly.Methods: In adult bioassay, conidia of entomopathogenic fungus were applied as inoculated bait at 105 and 107 spore per gram and spinosad at 0.5, 1 and 1.5 µg (A.I. per gram bait. In larval bioassay, conidia were applied as combina­tion of spore with larval bedding at 106 and 108 spore per gram and spinosad at sublethals of 0.002, 0.004 and 0.006 µg (AI per gram medium. Results: Adult mortality was 48% and 72% for fungus alone but ranged from 66–87% and 89–95% in combination treat­ments of 105 and 107 spore/g with sublethal doses of spinosad respectively. The interaction between 105 spore/g with sublethals exhibited synergistic effect, but in combination of 107 spore in spite of higher mortality, the interac­tion was additive. There was significant difference in LT50 among various treatments. LT50 values in all combination treat­ments were smaller than LT50 values in alone ones. Larval mortality was 36% and 69% for fungus alone but ranged from 58%–78% and 81%–100% in combination treatments of 106 and 108 spore/g medium with sublethals of spino­sad respectively. The interaction was synergistic in all combination treatments of larvae.Conclusion: The interaction between M. anispliae and spinosad indicated a synergetic effect that increased the house fly mortality as well as reduced the lethal time.

  12. Assessment of Sublethal and Transgenerational Effects of Pirimicarb on the Wheat Aphids Rhopalosiphum padi and Sitobion avenae

    Science.gov (United States)

    Desneux, Nicolas; Han, Peng; Gao, Xiwu

    2015-01-01

    The wheat aphids, Rhopalosiphum padi (Linnaeus) and Sitobion avenae (Fabricius), are key pests on wheat crops worldwide. Management practices rely primarily on insecticides. The pirimicarb (carbamate) is used extensively as an effective insecticide to control these two aphids. In addition to the mortality caused by pirimicarb, various sublethal effects may occur in aphids when exposed to low lethal or sublethal doses. Understanding the general effect of pirimicarb on aphids could help increasing rational use of this insecticide. Under laboratory conditions, we assessed the sublethal effects of a low lethal concentration of pirimicarb (LC25) on biological traits and acetylcholinesterase (AChE) activity of R. padi and S. avenae. Both direct and transgenerational effects, i.e. on parent and the F1 generations were assessed, respectively. We found that R. padi and S. avenae responded differentially to the LC25 of pirimicarb. The parent generation of R. padi showed a 39% decrease in fecundity and multiple transgenerational effects were observed in the F1 generation; overall juvenile development, reproductive period, adult longevity and lifespan were longer than those of the control group. By contrast, LC25 of pirimicarb showed almost no effects on S. avenae biological traits in both the parent and F1 generations; only the pre-reproductive duration was reduced in F1 generations. Demographic parameter estimates (e.g. rm) showed similar trend, i.e. significant negative effect on R. padi population growth and no effect on S. avenae. However, AChE activity decreased in both R. padi and S. avenae treated by the LC25 of pirimicarb. We demonstrated sublethal and transgenerational effects of pirimicarb in the two wheat aphid species; it hinted at the importance of considering sublethal effects (including hormesis) of pirimicarb for optimizing Integrated Pest Management (IPM) of wheat aphids. PMID:26121265

  13. Acute toxicity and sublethal effects of gallic and pelargonic acids on the zebrafish Danio rerio.

    Science.gov (United States)

    Techer, Didier; Milla, Sylvain; Fontaine, Pascal; Viot, Sandrine; Thomas, Marielle

    2015-04-01

    Gallic and pelargonic acids are naturally found in a variety of plants and food products. Despite their extensive use in man-made applications, little is known regarding their potential risks to aquatic vertebrates. The aim of this work was to assess the acute toxicity of these polyphenolic and fatty acid compounds to the zebrafish. In order to get insights into sublethal effects, the enzyme activity of usual biomarkers related to oxidative stress and biotransformation were also assessed in fish. These latter included total superoxide dismutase, catalase as well as total glutathione peroxidase for antioxidant defence mechanisms and glutathione S-transferase for biotransformation related enzyme. Gallic acid was practically non-toxic (96-h lethal concentration (LC50) > 100 mg/L) whereas pelargonic acid was slightly toxic (96-h LC50 of 81.2 mg/L). Moreover, biomarker analyses indicated enhanced superoxide dismutase activity in fish exposed to 20, 40 and 100 mg/L of gallic acid compared to control. A dose-dependent induction of glutathione peroxidase and glutathione S-transferase was reported following gallic acid exposure at the tested concentrations of 10, 20 and 40 mg/L, with the exception of 100 mg/L of substance where basal activity levels were reported. In the case of pelargonic acid, there was no change in antioxidant enzyme activity while an inhibition of glutathione S-transferase was observed from organisms exposed to 45, 58 and 76 mg/L of test solution. The results concerning sublethal effects on biological parameters of zebrafish highlighted thereby the need for further investigations following chronic exposure to both organic acids.

  14. Use of sublethal endpoints in sediment toxicity tests with the amphipod Hyalella azteca

    Science.gov (United States)

    Ingersoll, Chris G.; Brunson, Eric L.; Dwyer, F. James; Hardesty, Douglas K.; Kemble, Nile E.

    1998-01-01

    Short-term sediment toxicity tests that only measure effects on survival can be used to identify high levels of contamination but may not be able to identify marginally contaminated sediments. The objective of the present study was to develop a method for determining the potential sublethal effects of contaminants associated with sediment on the amphipod Hyalella azteca (e.g., reproduction). Exposures to sediment were started with 7- to 8-d-old amphipods. On day 28, amphipods were isolated from the sediment and placed in water-only chambers where reproduction was measured on day 35 and 42. Typically, amphipods were first in amplexus at about day 21 to 28 with release of the first brood between day 28 to 42. Endpoints measured included survival (day 28, 35, and 42), growth (as length and weight on day 28 and 42), and reproduction (number of young/female produced from day 28 to 42). This method was used to evaluate a formulated sediment and field-collected sediments with low to moderate concentrations of contaminants. Survival of amphipods in these sediments was typically >85% after the 28-d sediment exposures and the 14-d holding period in water to measure reproduction. Reproduction was more variable than growth; hence, more replicates might be needed to establish statistical differences among treatments. Previous studies have demonstrated that growth of H. azteca in sediment tests often provides unique information that can be used to discriminate toxic effects of exposure to contaminants. Either length or weight can be measured in sediment tests with H. azteca. However, additional statistical options are available if length is measured on individual amphipods, such as nested analysis of variance that can account for variance in length within replicates. Ongoing water-only studies testing select contaminants will provide additional data on the relative sensitivity and variability of sublethal endpoints in toxicity tests with H. azteca.

  15. Stability of sublethal acid stress adaptation and induced cross protection against lauric arginate in Listeria monocytogenes.

    Science.gov (United States)

    Shen, Qian; Soni, Kamlesh A; Nannapaneni, Ramakrishna

    2015-06-16

    The stability of acid stress adaptation in Listeria monocytogenes and its induced cross protection effect against GRAS (generally recognized as safe) antimicrobial compounds has never been investigated before. In the present study, the acid stress adaptation in L. monocytogenes was initially induced in pH 5.0 tryptic soy broth supplemented with 0.6% yeast extract (TSB-YE) at 37 °C. Subsequently, the stability of acid stress adaptation, which was defined as the capacity to maintain its acquired acid adaptation after induction in the absence of sublethal acid stress, was determined at 37 °C, 22 °C or 4 °C in broth and in different food substrates. Then, the acid stress adaptation induced cross protection against lauric arginate (LAE) and its stability was investigated in TSB-YE, milk and carrot juice. Our findings show that the acid stress adaptation was stable at 4 °C up to 24h but was reversed at 37 °C or 22 °C within 2h. In the cross protection assay with LAE, the acid stress adapted cells had approximately 2 log CFU/ml greater survival than non-adapted cells in broth at 22 °C or in milk and carrot juice at 4 °C. The acid adaptation induced cross protection against LAE in L. monocytogenes was reversible within 1h at 4 °C in the absence of sublethal acid stress. Our findings suggest that the stability of acid adaptation in L. monocytogenes under cold conditions should be taken into account when the risk analysis is performed during food processing.

  16. Exposure to sublethal levels of PCB-126 impacts fuel metabolism and swimming performance in rainbow trout.

    Science.gov (United States)

    Bellehumeur, Karyne; Lapointe, Dominique; Cooke, Steven J; Moon, Thomas W

    2016-09-01

    Polychlorinated biphenyls (PCBs) are recognized physiological stressors to fish which over time may impair individual performance and perhaps fitness by inducing changes that could have population-level consequences. PCB-126 (3,3',4,4',5-pentachlorobiphenyl) accumulates in lipids and can subsequently be released into the bloodstream during periods of high activity that involve the mobilization of stored fuels to meet with increasing energy demands. The goal of this study was to determine if a sublethal exposure to PCB-126 altered the content of tissue energy supplies (carbohydrates, proteins, amino acids, triglycerides) and impaired swimming performance as well as oxygen consumption in rainbow trout (Oncorhynchus mykiss). Trout were injected intraperitoneally with a single Low (100μgkg(-1)) or High (400μgkg(-1)) dose of PCB-126 then swimming performance and metabolic rates from 1 to 9days post-injection were compared to Control (non-dosed) fish. Liver ethoxyresorufin-O-deethylase (EROD) activity was assessed as an indication of PCB-126 intoxication while plasma and white muscle tissue metabolites were analyzed as an index of physiological disturbance. Swimming performance, assessed using two successive modified critical swimming speed (Ucrit) tests, was highest for fish in the High PCB-126 treatment; however, their initial condition factor (K) was also higher, largely due to their greater body mass. Trout in the High and Low PCB-126 treatments exhibited impaired recovery following intense exercise as they swam comparatively poorly when provided a second challenge. PCB-exposed fish exhibited reduced spleen somatic indices as well as muscle glucose and glycogen contents; whereas plasma cortisol and glucose levels were elevated, indicating higher metabolic costs during recovery and muscle restoration. Overall, this research provides insights into the sublethal effects of a toxic organic compound on swimming performance in trout.

  17. Mortality, temporary sterilization, and maternal effects of sublethal heat in bed bugs.

    Directory of Open Access Journals (Sweden)

    Bjørn Arne Rukke

    Full Text Available Adult bed bugs were exposed to the sublethal temperatures 34.0°C, 35.5°C, 37.0°C, 38.5°C, or 40.0°C for 3, 6, or 9 days. The two uppermost temperatures induced 100% mortality within 9 and 2 days, respectively, whereas 34.0°C had no observable effect. The intermediate temperatures interacted with time to induce a limited level of mortality but had distinct effects on fecundity, reflected by decreases in the number of eggs produced and hatching success. Adult fecundity remained low for up to 40 days after heat exposure, and the time until fertility was restored correlated with the temperature-sum experienced during heat exposure. Three or 6 days of parental exposure to 38.5°C significantly lowered their offspring's feeding and moulting ability, which consequently led to a failure to continue beyond the third instar. Eggs that were deposited at 22.0°C before being exposed to 37.0°C for 3 or 6 days died, whereas eggs that were exposed to lower temperatures were not significantly affected. Eggs that were deposited during heat treatment exhibited high levels of mortality also at 34.0°C and 35.5°C. The observed negative effects of temperatures between 34.0°C and 40.0°C may be utilized in pest management, and sublethal temperature exposure ought to be further investigated as an additional tool to decimate or potentially eradicate bed bug populations. The effect of parental heat exposure on progeny demonstrates the importance of including maternal considerations when studying bed bug environmental stress reactions.

  18. Mortality, temporary sterilization, and maternal effects of sublethal heat in bed bugs.

    Science.gov (United States)

    Rukke, Bjørn Arne; Aak, Anders; Edgar, Kristin Skarsfjord

    2015-01-01

    Adult bed bugs were exposed to the sublethal temperatures 34.0°C, 35.5°C, 37.0°C, 38.5°C, or 40.0°C for 3, 6, or 9 days. The two uppermost temperatures induced 100% mortality within 9 and 2 days, respectively, whereas 34.0°C had no observable effect. The intermediate temperatures interacted with time to induce a limited level of mortality but had distinct effects on fecundity, reflected by decreases in the number of eggs produced and hatching success. Adult fecundity remained low for up to 40 days after heat exposure, and the time until fertility was restored correlated with the temperature-sum experienced during heat exposure. Three or 6 days of parental exposure to 38.5°C significantly lowered their offspring's feeding and moulting ability, which consequently led to a failure to continue beyond the third instar. Eggs that were deposited at 22.0°C before being exposed to 37.0°C for 3 or 6 days died, whereas eggs that were exposed to lower temperatures were not significantly affected. Eggs that were deposited during heat treatment exhibited high levels of mortality also at 34.0°C and 35.5°C. The observed negative effects of temperatures between 34.0°C and 40.0°C may be utilized in pest management, and sublethal temperature exposure ought to be further investigated as an additional tool to decimate or potentially eradicate bed bug populations. The effect of parental heat exposure on progeny demonstrates the importance of including maternal considerations when studying bed bug environmental stress reactions.

  19. Detecting and Correcting Speech Repairs

    CERN Document Server

    Heeman, P A; Heeman, Peter; Allen, James

    1994-01-01

    Interactive spoken dialog provides many new challenges for spoken language systems. One of the most critical is the prevalence of speech repairs. This paper presents an algorithm that detects and corrects speech repairs based on finding the repair pattern. The repair pattern is built by finding word matches and word replacements, and identifying fragments and editing terms. Rather than using a set of prebuilt templates, we build the pattern on the fly. In a fair test, our method, when combined with a statistical model to filter possible repairs, was successful at detecting and correcting 80\\% of the repairs, without using prosodic information or a parser.

  20. Influence of epidermal growth factor receptor monoclony antibody MAb225 on DNA repair of tongue carcinoma cell after radiation%表皮生长因子受体单抗MAb225对舌癌细胞DNA放射后损伤修复的影响

    Institute of Scientific and Technical Information of China (English)

    王明国; 王中和

    2011-01-01

    Objective The objective of this study is to investigate the effect of epidermal growth factor receptor (EGFR) monoclonal antibody MAb225 on repair of DNA double strand break (DNA-DSB) after radiation in tongue squamous cell carcinoma cell. Methods The single cell gel electrophoresis(SCGE) was performed to estimate the repair of DNA-DSB induced by radiation in human tongue carcinoma cells Tca8113 treated with or without MAb225. Expression of Ku70 and Ku80 were detected by semiquantitative reverse transcription polymerase chain reaction and Western bolt Results Comet tail moment of MAb225 treated cell was significantly higher than untreated cell(P<0.05). The expression of Ku70 and Ku80 were inhibited by MAb225. Conclusion MAb225 can inhibit repair of DNA-DSB induced by down-regulated expression of Ku70 and Ku80.%目的 研究表皮生长因子受体(EGFR)单克隆抗体MAb225对放射所致舌癌细胞DNA损伤修复的影响及其作用机制.方法 应用单细胞凝胶电泳的方法检测MAb225对舌鳞癌细胞Tca8113放射后DNA双链断裂所致的尾矩,半定量逆转录多聚酶链反应和Western blot检测MAb225对DNA蛋白激酶Ku70、Ku80表达的影响.结果 MAb225作用后的细胞单细胞凝胶电泳的彗星尾矩明显高于未处理细胞(P<0.05),并能显著抑制DNA蛋白激酶Ku70、Ku80的表达.结论 MAb225通过抑制DNA蛋白激酶Ku70、Ku80的表达影响了DNA双链断裂的修复能力.

  1. Induction and stability of oxidative stress adaptation in Listeria monocytogenes EGD (Bug600) and F1057 in sublethal concentrations of H2O2 and NaOH.

    Science.gov (United States)

    De Abrew Abeysundara, Piumi; Nannapaneni, Ramakrishna; Soni, Kamlesh A; Sharma, Chander S; Mahmoud, Barakat

    2016-12-05

    Food processing and food handling environments may contain residual levels of sanitizers or cleaners which may trigger oxidative stress adaptation in Listeria monocytogenes. The aim of this study was to determine the induction and stability of oxidative stress adaptation in L. monocytogenes EGD (Bug600) (serotype 1/2a) and F1057 (serotype 4b) at different concentrations and times of sublethal oxidative stress induced by H2O2 or sublethal alkali stress induced by NaOH at 37°C. Both L. monocytogenes Bug600 and F1057 strains showed significantly higher survival in lethal oxidative stress (1000ppm H2O2) after pre-exposure to 50ppm H2O2 for 30min compared to control cells (no pre-exposure to H2O2). When the cells were pre-exposed to sublethal alkali stress by NaOH, the oxidative stress adaptation was induced within 5min in L. monocytogenes. The survival of both L. monocytogenes strains was increased by 2 to 4.5 logs in lethal oxidative stress when the cells were pre-exposed to sublethal alkali stress at pH9 from 5 to 120min by NaOH compared to control cells (no pre-exposure to sublethal alkali pH). Two other alkali reagents tested (KOH and NH4OH) also induced oxidative stress adaptation in L. monocytogenes. For both L. monocytogenes strains, the oxidative stress adaptation induced by sublethal H2O2 was reversible in 30min and that induced by sublethal alkali stress was reversible within 60min at 37°C in the absence of such sublethal stress. These findings show that sublethal oxidative or alkali stress conditions can induce oxidative stress adaptation that may increase the risk of survival of L. monocytogenes cells in lethal oxidative stress.

  2. DNA base excision repair nanosystem engineering: model development.

    Science.gov (United States)

    Sokhansanj, B A

    2005-01-01

    DNA base damage results from a combination of endogenous sources, (normal metabolism, increased metabolism due to obesity, stress from diseases such as arthritis and diabetes, and ischemia) and the environment (ingested toxins, ionizing radiation, etc.). If unrepaired DNA base damage can lead to diminished cell function, and potentially diseases and eventually mutations that lead to cancer. Sophisticated DNA repair mechanisms have evolved in all living cells to preserve the integrity of inherited genetic information and transcriptional control. Understanding a system like DNA repair is greatly enhanced by using engineering methods, in particular modeling interactions and using predictive simulation to analyze the impact of perturbations. We describe the use of such a "nanosystem engineering" approach to analyze the DNA base excision repair pathway in human cells, and use simulation to predict the impact of varying enzyme concentration on DNA repair capacity.

  3. Groin hernia repair in young males: mesh or sutured repair?

    DEFF Research Database (Denmark)

    Bisgaard, T; Bay-Nielsen, M; Kehlet, H

    2010-01-01

    Large-scale data for the optimal inguinal hernia repair in younger men with an indirect hernia is not available. We analysed nationwide data for risk of reoperation in younger men after a primary repair using a Lichtenstein operation or a conventional non-mesh hernia repair....

  4. Cleft lip and palate repair

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002979.htm Cleft lip and palate repair To use the sharing features on this page, please enable JavaScript. Cleft lip and cleft palate repair is surgery to fix birth defects ...

  5. Abdominal aortic aneurysm repair - open

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007392.htm Abdominal aortic aneurysm repair - open To use the sharing features on this page, please enable JavaScript. Open abdominal aortic aneurysm repair is surgery to fix a widened part ...

  6. Nanomaterials promise better bone repair

    OpenAIRE

    Qifei Wang; Jianhua Yan; Junlin Yang; Bingyun Li

    2016-01-01

    Nanomaterials mimicking the nano-features of bones and offering unique smart functions are promising for better bone fracture repair. This review provides an overview of the current state-of-the-art research in developing and using nanomaterials for better bone fracture repair. This review begins with a brief introduction of bone fracture repair processes, then discusses the importance of vascularization, the role of growth factors in bone fracture repair, and the failure of bone fracture rep...

  7. Laparoscopic repair of femoral hernia

    OpenAIRE

    Yang, Xue-Fei; Liu, Jia-Lin

    2016-01-01

    Laparoscopic repair of inguinal hernia is mini-invasive and has confirmed effects. Femoral hernia could be repaired through the laparoscopic procedures for inguinal hernia. These procedures have clear anatomic view in the operation and preoperatively undiagnosed femoral hernia could be confirmed and treated. Lower recurrence ratio was reported in laparoscopic procedures compared with open procedures for repair of femoral hernia. The technical details of laparoscopic repair of femoral hernia, ...

  8. Aircraft Propeller Hub Repair

    Energy Technology Data Exchange (ETDEWEB)

    Muth, Thomas R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Peter, William H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-02-13

    The team performed a literature review, conducted residual stress measurements, performed failure analysis, and demonstrated a solid state additive manufacturing repair technique on samples removed from a scrapped propeller hub. The team evaluated multiple options for hub repair that included existing metal buildup technologies that the Federal Aviation Administration (FAA) has already embraced, such as cold spray, high velocity oxy-fuel deposition (HVOF), and plasma spray. In addition the team helped Piedmont Propulsion Systems, LLC (PPS) evaluate three potential solutions that could be deployed at different stages in the life cycle of aluminum alloy hubs, in addition to the conventional spray coating method for repair. For new hubs, a machining practice to prevent fretting with the steel drive shaft was recommended. For hubs that were refurbished with some material remaining above the minimal material condition (MMC), a silver interface applied by an electromagnetic pulse additive manufacturing method was recommended. For hubs that were at or below the MMC, a solid state additive manufacturing technique using ultrasonic welding (UW) of thin layers of 7075 aluminum to the hub interface was recommended. A cladding demonstration using the UW technique achieved mechanical bonding of the layers showing promise as a viable repair method.

  9. γ-H2AX分析电离辐射诱发小鼠神经元DNA双链断裂及修复%Ionizing radiation-induced DNA double-strand break and repair assessed by γ-H2AX roci analysis in neurons in mice

    Institute of Scientific and Technical Information of China (English)

    董晓荣; Ruebe Claudia; Ruebe Christian; 伍钢

    2009-01-01

    -deficient mouse strains (BALB/c, A-T and SCID mice) were analyzed at 0.5, 2.5, 5, 24 and 48 h after whole-body irradiation with 2 Gy. The mature neurons in the neocortex of brain tissue of sham-irradiated mice of each strain served as controls. γ-H2AX immunohistochemistry and γ-H2AX and NeuN double immunofluorescence analysis was used to measure DSBs formation and repair in the mature neurons in the neocortex of brain tissue of the different mouse strains. Results For the DSB formation experiment, γ-H2AX foci levels with a clear linear dose correlation and very low backgrounds in the nuclei in the neocortex of brain tissue were observed. Scoring the loss of γ-H12AX foci allowed us to verify the different, genetically determined DSB repair deficiencies, including the minor impairment of BALB/c mice. Repair-proficient C57BL/6 mice exhibited the fastest decrease in foei number with time, and displayed low levels of residual damage at 24 h and 48 h post-irradiation. In contrast, SCID mice showed highly increased γ-H2AX foci levels at all repair times (0.5 h to 48 h) while A-T mice exhibited a lesser defect which was most significant at later repair times (≥ 5 h). Radiosensitive BALB/c mice exhibited slighdy elevated foei numbers compared with C57BI./6 mice at 5 h and 24 h but not at 48 h post-irradiation. Conclusion Quantifying the γ-H2AX loci in normal tissue represents a sensitive tool for the detection of induction and repair of radiation-induced DSBs at clinically relevant doses in vivo.

  10. Development of a New Technique to Assess Susceptibility to Predation Resulting from Sublethal Stresses (Indirect Mortality)

    Energy Technology Data Exchange (ETDEWEB)

    Cada, G.F.

    2003-08-25

    Fish that pass through a hydroelectric turbine may not be killed directly, but may nonetheless experience sublethal stresses that will increase their susceptibility to predators (indirect mortality). There is a need to develop reliable tests for indirect mortality so that the full consequences of passage through turbines (and other routes around a hydroelectric dam) can be assessed. We evaluated a new technique for assessing indirect mortality, based on a behavioral response to a startling stimulus (akin to perceiving an approaching predator). We compare this technique to the standard predator preference test. The behavioral response is a rapid movement commonly referred to as a startle response, escape response, or C-shape, based on the characteristic body position assumed by the fish. When viewed from above, a startled fish bends into a C-shape, then springs back and swims away in a direction different from its original orientation. This predator avoidance (escape) behavior can be compromised by sublethal stresses that temporarily stun or disorient the fish. We subjected striped shiners and fathead minnows to varying intensities of either turbulence (10-, 20- or 30-min) or 2-min exposures to a fish anesthetic (100 or 200 mg/L of tricaine methanesulfonate), and evaluated their subsequent behavior. Individual fish were given a startle stimulus and filmed with a high-speed video camera. Each fish was startled and filmed twice before being stressed, and then at 1-, 5-, 15-, and 30-min post-exposure. The resulting image files were analyzed for a variety of behavioral measures including: presence of a response, time to first reaction, duration of reaction, time to formation of maximum C-shape, time to completion of C-shape, and completeness of C-shape. The most immediate measure of potential changes in fish behavior was whether stressed fish exhibited a startle response. For striped shiners, the number of fish not responding to the stimulus was significantly different

  11. Assessing Sub-Lethal Impacts of Petroleum Compounds on Marine Benthic Systems

    Energy Technology Data Exchange (ETDEWEB)

    Lindgren, J. Fredrik

    2012-07-01

    Petroleum and its different distillates commonly end up in the marine environment. One source of these additions is discharges originating from shipping activities; accidents, ship wrecks, operational spills etc. Depending on several different factors that govern the fate of petroleum released into the marine environment the effects of the discharge will differ, from acute toxic to long term sub-lethal effects. While effects on biota from large spills have thoroughly been investigated in the past long term sub-lethal effects are somewhat less examined. Therefore the objective of this thesis has been to develop and apply a method to analyze what effects low concentrations of petroleum, which often ends up in marine sediments, have on benthic sediment biota. Ecotoxicological endpoints that were evaluated were density changes of meiofauna and variations in the microbial community function, measured as inorganic nutrient fluxes over the sediment-water interface the potential to perform a metabolic process. These types of organisms are two important key players in marine benthic sedimentary habitats, performing ecosystem services such as degradation of organic matter, recycling of nutrients and various pollutants and they constitute a carbon link to higher trophic levels. As manual classification of meiofauna is very time-consuming process including an extended learning process for the taxonomist, this thesis is in its first part focused at the field of automatic classification. To classify meiofaunal communities a novel technique was developed where the image analysis software ZooImage was adapted to automatically classify higher taxonomic taxa of meiofauna, with successful results. The technique was evaluated by classifying meiofaunal communities from five different depths in the Gullmar Fjord, Sweden. The accuracy of the analyses was tested using ZooImage's internal 10-fold cross-validation method, and by comparing digitalized samples from the different sites

  12. Role of splenic stroma in the action of bacterial lipopolysaccharides on radiation mortality: a study in mice carrying the Slj allele

    NARCIS (Netherlands)

    R.E. Ploemacher (Robert); N.H.C. Brons (Nicolaas)

    1987-01-01

    textabstractAbstract. Slj/+ mice display a slight macrocytic anaemia due to a defect in their haemopoietic organ stroma. They have a deficient endogenous spleen colony (CFU‐end) formation following sublethal doses of gamma‐radiation compared with their normal +/+ littermates, which is likely to be

  13. Role of splenic stroma in the action of bacterial lipopolysaccharides on radiation mortality: a study in mice carrying the Slj allele

    NARCIS (Netherlands)

    R.E. Ploemacher (Robert); N.H.C. Brons (Nicolaas)

    1987-01-01

    textabstractAbstract. Slj/+ mice display a slight macrocytic anaemia due to a defect in their haemopoietic organ stroma. They have a deficient endogenous spleen colony (CFU‐end) formation following sublethal doses of gamma‐radiation compared with their normal +/+ littermates, which is likely to be d

  14. Joint toxicity of permethrin and cypermethrin at sublethal concentrations to the embryo-larval zebrafish.

    Science.gov (United States)

    Yang, Ye; Ma, Huihui; Zhou, Jinghua; Liu, Jing; Liu, Weiping

    2014-02-01

    Pyrethroids, the widely used pesticides, are highly toxic to aquatic organisms. However, little information is so far available regarding the joint toxicity of type I and type II pyrethroids to fish. Zebrafish is a well-accepted aquatic vertebrate model for toxicity assessment due to small size, easy husbandry, high fecundity and transparent embryos. In this study, we utilized embryo-larval zebrafish to elucidate the combined effects of sublethal concentrations of permethrin (PM) and cypermethrin (CP), which are the most frequently used type I and type II pyrethroids, respectively. Fish were exposed from 3h postfertilization (hpf) to 144 hpf to binary mixtures of nominal concentrations of 100, 200, 300μgL(-1) PM (PM100, PM200, PM300) and 10, 20, 30μgL(-1) CP (CP10, CP20, CP30). Analytical data of the real concentrations of the chemicals showed a significant degradation of the pyrethroids but an obvious recovery after the renewal of the exposure solution. Defect rates of embryos exposed to these low concentrations of single PM or CP exhibited no statistically significant difference from the control,while the application of combination of PM and CP resulted in deleterious effects on zebrafish embryonic development. In all PM200 and PM300 exposure groups, increasing CP concentrations acted additively to the action of PM in terms of all sublethal endpoints. Co-treatment of embryos with the specific sodium channel blocker MS-222 and pyrethroids (individuals or the mixture) caused a decline in the incidences of body axis curvature and spasms compared to treatment of animals with pyrethroids alone, suggesting that the developmental toxicity of PM and CP to zebrafish was related to disruption of ion channels. We further revealed that mixture of the two pyrethroids caused greater down-regulation in the mRNA levels of proneural genes. The individual pesticides had no effect on the activity of superoxide dismutase (SOD), while the mixture exposure caused significant

  15. Transcriptomic analysis of RDX and TNT interactive sublethal effects in the earthworm Eisenia fetida

    Science.gov (United States)

    Gong, Ping; Guan, Xin; Inouye, Laura S; Deng, Youping; Pirooznia, Mehdi; Perkins, Edward J

    2008-01-01

    Background Explosive compounds such as TNT and RDX are recalcitrant contaminants often found co-existing in the environment. In order to understand the joint effects of TNT and RDX on earthworms, an important ecological and bioindicator species at the molecular level, we sampled worms (Eisenia fetida) exposed singly or jointly to TNT (50 mg/kg soil) and RDX (30 mg/kg soil) for 28 days and profiled gene expression in an interwoven loop designed microarray experiment using a 4k-cDNA array. Lethality, growth and reproductive endpoints were measured. Results Sublethal doses of TNT and RDX had no significant effects on the survival and growth of earthworms, but significantly reduced cocoon and juvenile counts. The mixture exhibited more pronounced reproductive toxicity than each single compound, suggesting an additive interaction between the two compounds. In comparison with the controls, we identified 321 differentially expressed transcripts in TNT treated worms, 32 in RDX treated worms, and only 6 in mixture treated worms. Of the 329 unique differentially expressed transcripts, 294 were affected only by TNT, 24 were common to both TNT and RDX treatments, and 3 were common to all treatments. The reduced effects on gene expression in the mixture exposure suggest that RDX might interact in an antagonistic manner with TNT at the gene expression level. The disagreement between gene expression and reproduction results may be attributed to sampling time, absence of known reproduction-related genes, and lack of functional information for many differentially expressed transcripts. A gene potentially related to reproduction (echinonectin) was significantly depressed in TNT or RDX exposed worms and may be linked to reduced fecundity. Conclusions Sublethal doses of TNT and RDX affected many biological pathways from innate immune response to oogenesis, leading to reduced reproduction without affecting survival and growth. A complex interaction between mixtures of RDX and TNT was

  16. Applicability of the TCDD-TEQ approach to predict sublethal embryotoxicity in Fundulus heteroclitus.

    Science.gov (United States)

    Rigaud, Cyril; Couillard, Catherine M; Pellerin, Jocelyne; Légaré, Benoît; Hodson, Peter V

    2014-04-01

    The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalent quantity (TCDD-TEQ) approach was used successfully to predict lethal embryotoxicity in salmonids, but its applicability to sublethal effects of mixtures of organohalogenated compounds in other fish species is poorly known. The sublethal toxicity of two dioxin-like compounds (DLCs), 3,3',4,4'-tetrachlorobiphenyl (PCB77) and 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PnCDF), two non-dioxin-like (NDL) polychlorinated biphenyls (PCBs), 2,2',5,5'-tetrachlorobiphenyl (PCB52) and 2,3,3',4',6-pentachlorobiphenyl (PCB110), and of Aroclor 1254, a complex commercial mixture of PCBs, was assessed in Fundulus heteroclitus embryos exposed by intravitelline injection. At 16 days post-fertilization, the two DLCs and Aroclor 1254 altered prey capture ability in addition to inducing classical aryl hydrocarbon receptor-mediated responses: ethoxyresorufin-O-deethylase (EROD) induction, craniofacial deformities and reduction in body length. None of these responses was induced by the two NDL PCBs, at doses up to 5400 ng g(-1)wet weight. Dose-response curves for prey capture ability for the 2 DLCs tested were not parallel to that of TCDD, violating a fundamental assumption for relative potency (ReP) estimation. Dose-response curves for EROD induction were parallel for 2,3,4,7,8-PnCDF and TCDD, but the ReP of 2,3,4,7,8-PnCDF for F. heteroclitus was 5-fold higher than the World Health Organization (WHO) fish toxic equivalent factor (TEF) based on embryolethality in salmonids. The chemically derived TCDD-TEQs of Aroclor 1254, calculated using 3,3',4,4',5-pentachlorobiphenyl (PCB126) concentrations and it ReP for F. heteroclitus, overestimated its potency to induce EROD activity possibly due to antagonistic interactions among PCBs. This study highlights the limitations of using TEFs based on salmonid toxicity data alone for risk assessment to other fish species. There is a need to assess the variability of RePs of DLCs in

  17. Biological effects of exposure to intermediate neutron and repair mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Utsumi, Hiroshi; Sasaki, Masao [Kyoto Univ. (Japan); Onishi, Takeo; Onizuka, Masahiko

    2000-01-01

    An investigation was made on cytotoxic effects of neutron capture using chicken B-cell line mutants, DT40, KURO{sup -/-}, RAD54 {sup -/-} and KU70{sup -/-} / RAD54{sup -/-}. Suspensions of these cells were exposed to two times X-radiation at various doses and the cell surviving was evaluated. The sensitivity to radiation was highest in the double defective mutant, KU70{sup -/-} / RAD54{sup -/-} and followed by that of RAD54 {sup -/-}, a homologous recombination mutant, whereas KURO {sup -/-} cell, a non-homologous end-joining mutant showed a peculiar surviving curve composed of two phases and the cell was highly sensitive to a low-dose radiation. This indicates that there are two different DNA repair systems for double-strand breaks and the system for non-homologous end-joining repair can be involved in all phases of cell cycle, but the system for the homologous one is involved only in S-phase. Therefore, it was thought that variation of sensitivity to radiation exposure depending to the phase of cell cycle might explain the alternation of repair system depending to the phase progressing of cell cycle. It was thus likely that the recovery from radiation injury, which is still a black box might be explained with the double strand breaks of DNA. (M.N.)

  18. Sublethal pesticide doses negatively affect survival and the cellular responses in American foulbrood-infected honeybee larvae

    Science.gov (United States)

    López, Javier Hernández; Krainer, Sophie; Engert, Antonia; Schuehly, Wolfgang; Riessberger-Gallé, Ulrike; Crailsheim, Karl

    2017-02-01

    Disclosing interactions between pesticides and bee infections is of most interest to understand challenges that pollinators are facing and to which extent bee health is compromised. Here, we address the individual and combined effect that three different pesticides (dimethoate, clothianidin and fluvalinate) and an American foulbrood (AFB) infection have on mortality and the cellular immune response of honeybee larvae. We demonstrate for the first time a synergistic interaction when larvae are exposed to sublethal doses of dimethoate or clothianidin in combination with Paenibacillus larvae, the causative agent of AFB. A significantly higher mortality than the expected sum of the effects of each individual stressor was observed in co-exposed larvae, which was in parallel with a drastic reduction of the total and differential hemocyte counts. Our results underline that characterizing the cellular response of larvae to individual and combined stressors allows unmasking previously undetected sublethal effects of pesticides in colony health.

  19. Evaluation of Pyrethrin Formulations on Dengue/Dengue Haemorrhagic Fever Vectors in the Laboratory and Sublethal Effects

    Directory of Open Access Journals (Sweden)

    S Sulaiman

    2007-12-01

    Full Text Available In Southeast Asia, Aedes aegypti (L. has been incriminated as principal vector of dengue viruses and Ae. albopictus as the secondary vector of dengue fever. Therefore, the aim of this study was to investigate the effectiveness of three for-mula¬tions of pyrethrin derived from Tanacetum cinerariaefolium against the dengue/dengue haemorrhagic fever vectors Aedes aegypti and Ae. albopictus in the laboratory. The testings employed 2 methodologies: the WHO Larval Bioassay and WHO Adult Bioassay. The results showed that all the three pyrethrin formulations had larvicidal and adulticidal activi-ties. The impact of the sublethal doses of pyrethrin formulations on Aedes spp. larvae resulted in 4-6% of alive adult emergence compared to 90% of Ae. aegypti emerging adults and 96% Ae. albopictus alive adult emergence in the control. The impact of sublethal doses of the pyrethrin formulations caused very low fecundity on both Aedes spp. compared to the control (P< 0.05.

  20. Sublethal pesticide doses negatively affect survival and the cellular responses in American foulbrood-infected honeybee larvae

    Science.gov (United States)

    López, Javier Hernández; Krainer, Sophie; Engert, Antonia; Schuehly, Wolfgang; Riessberger-Gallé, Ulrike; Crailsheim, Karl

    2017-01-01

    Disclosing interactions between pesticides and bee infections is of most interest to understand challenges that pollinators are facing and to which extent bee health is compromised. Here, we address the individual and combined effect that three different pesticides (dimethoate, clothianidin and fluvalinate) and an American foulbrood (AFB) infection have on mortality and the cellular immune response of honeybee larvae. We demonstrate for the first time a synergistic interaction when larvae are exposed to sublethal doses of dimethoate or clothianidin in combination with Paenibacillus larvae, the causative agent of AFB. A significantly higher mortality than the expected sum of the effects of each individual stressor was observed in co-exposed larvae, which was in parallel with a drastic reduction of the total and differential hemocyte counts. Our results underline that characterizing the cellular response of larvae to individual and combined stressors allows unmasking previously undetected sublethal effects of pesticides in colony health. PMID:28145462

  1. Histopathological alterations in the kidney of Caspian kutum, Rutilus frisii kutum, larvae and fingerlings exposed to sublethal concentration of atrazine.

    Science.gov (United States)

    Khoshnood, Zahra

    2015-02-01

    The use of chemical pesticides has increased environmental pollution and affected ichthyofauna as non target organisms. In the present study, the histopathological alterations in the larvae and fingerlings of the Caspian kutum, Rutilus frisii kutum, were used as a model to investigate the toxic effects of triazine herbicide, atrazine. To investigate toxic effects of atrazine, fish were exposed to sublethal concentration of ½ LC50 for 96 h. Histologically, the most significant alterations in kidney tissues were hyperplasia, necrosis, vacuolation, swelling, hypertrophy, aggregation of hyaline droplets, and disruption of the haematopitic tissue of the head kidney. The damage was more severe in larvae than the fingerlings. Results showed that alterations in kidney tissue caused by atrazine were not specific but it could be concluded that atrazine is excessively toxic for Caspian kutum even at sublethal concentration and acute exposure.

  2. Nanomaterials promise better bone repair

    Directory of Open Access Journals (Sweden)

    Qifei Wang

    2016-10-01

    Full Text Available Nanomaterials mimicking the nano-features of bones and offering unique smart functions are promising for better bone fracture repair. This review provides an overview of the current state-of-the-art research in developing and using nanomaterials for better bone fracture repair. This review begins with a brief introduction of bone fracture repair processes, then discusses the importance of vascularization, the role of growth factors in bone fracture repair, and the failure of bone fracture repair. Next, the review discusses the applications of nanomaterials for bone fracture repair, with a focus on the recent breakthroughs such as nanomaterials leading to precise immobilization of growth factors at the molecular level, promoting vascularization without the use of growth factors, and re-loading therapeutic agents after implantation. The review concludes with perspectives on challenges and future directions for developing nanomaterials for improved bone fracture repair.

  3. Do biopesticides affect the demographic traits of a parasitoid wasp and its biocontrol services through sublethal effects?

    Directory of Open Access Journals (Sweden)

    Antonio Biondi

    Full Text Available Pesticide risk assessments are usually based on short-term acute toxicity tests, while longer-term population dynamic related traits, critical to the success of biological control and Integrated Pest Management (IPM programs, are often overlooked. This is increasingly important with respect to new biopesticides that frequently cause no short-term acute effects, but that can induce multiple physiological and behavioral sublethal effects, leading to a decrease in population growth and ecosystem services. In this study we assessed the lethal and sublethal effects of six biopesticides [abamectin, azadirachtin, Bacillus thuringiensis, borax plus citrus oil (Prev-Am®, emamectin benzoate, and spinosad], used in tomato crops to control the invasive pest Tuta absoluta (Lepidoptera: Gelechiidae, on adults and pupae of the parasitoid Bracon nigricans (Hymenoptera: Braconidae. Data on female survival and production of female offspring were used to calculate population growth indexes as a measure of population recovery after pesticide exposure. Spinosad caused 100% and 80% mortality in exposed adults (even 10 d after the treatment and pupae, respectively. Although most of the biopesticides had low levels of acute toxicity, multiple sublethal effects were observed. The biocontrol activity of both females that survived 1-h and 10-d old residues, and females that emerged from topically treated pupae was significantly affected by the application of the neurotoxic insecticides emamectin benzoate and abamectin. Furthermore, very low B. nigricans demographic growth indices were estimated for these two insecticides, indicating potential local extinction of the wasp populations. Among the tested products, Bt proved to be the safest for B. nigricans adults and pupae. Our findings emphasize that acute toxicity assessment alone cannot fully predict the actual impact of pesticides on non-target parasitoids. Thus, sublethal effects related to the species specific life

  4. Sub-lethal glyphosate exposure alters flowering phenology and causes transient male-sterility in Brassica spp

    OpenAIRE

    Londo, Jason Paul; McKinney, John; Schwartz, Matthew; Bollman, Mike; Sagers, Cynthia; Watrud, Lidia

    2014-01-01

    Background Herbicide resistance in weedy plant populations can develop through different mechanisms such as gene flow of herbicide resistance transgenes from crop species into compatible weedy species or by natural evolution of herbicide resistance or tolerance following selection pressure. Results from our previous studies suggest that sub-lethal levels of the herbicide glyphosate can alter the pattern of gene flow between glyphosate resistant Canola®, Brassica napus, and glyphosate sensitiv...

  5. DNA repair: Dynamic defenders against cancer and aging

    Energy Technology Data Exchange (ETDEWEB)

    Fuss, Jill O.; Cooper, Priscilla K.

    2006-04-01

    You probably weren't thinking about your body's cellular DNA repair systems the last time you sat on the beach in the bright sunshine. Fortunately, however, while you were subjecting your DNA to the harmful effects of ultraviolet light, your cells were busy repairing the damage. The idea that our genetic material could be damaged by the sun was not appreciated in the early days of molecular biology. When Watson and Crick discovered the structure of DNA in 1953 [1], it was assumed that DNA is fundamentally stable since it carries the blueprint of life. However, over 50 years of research have revealed that our DNA is under constant assault by sunlight, oxygen, radiation, various chemicals, and even our own cellular processes. Cleverly, evolution has provided our cells with a diverse set of tools to repair the damage that Mother Nature causes. DNA repair processes restore the normal nucleotide sequence and DNA structure of the genome after damage [2]. These responses are highly varied and exquisitely regulated. DNA repair mechanisms are traditionally characterized by the type of damage repaired. A large variety of chemical modifications can alter normal DNA bases and either lead to mutations or block transcription if not repaired, and three distinct pathways exist to remove base damage. Base excision repair (BER) corrects DNA base alterations that do not distort the overall structure of the DNA helix such as bases damaged by oxidation resulting from normal cellular metabolism. While BER removes single damaged bases, nucleotide excision repair (NER) removes short segments of nucleotides (called oligonucleotides) containing damaged bases. NER responds to any alteration that distorts the DNA helix and is the mechanism responsible for repairing bulky base damage caused by carcinogenic chemicals such as benzo [a]pyrene (found in cigarette smoke and automobile exhaust) as well as covalent linkages between adjacent pyrimidine bases resulting from the ultraviolet

  6. BRCA1 Mutation: A Predictive Marker for Radiation Therapy?

    Energy Technology Data Exchange (ETDEWEB)

    Kan, Charlene; Zhang, Junran, E-mail: Junran.zhang@case.edu

    2015-10-01

    DNA repair, in particular, DNA double-strand break (DSB) repair, is essential for the survival of both normal and cancer cells. An elaborate repair mechanism has been developed in cells to efficiently repair the damaged DNA. The pathways predominately involved in DSB repair are homologous recombination and classic nonhomologous end-joining, although the alternative NHEJ pathway, a third DSB repair pathway, could also be important in certain contexts. The protein of BRCA1 encoded by the tumor suppressor gene BRCA1 regulates all DSB repair pathways. Given that DSBs represent the most biologically significant lesions induced by ionizing radiation and that impaired DSB repair leads to radiation sensitivity, it has been expected that cancer patients with BRCA1 mutations should benefit from radiation therapy. However, the clinical data have been conflicting and inconclusive. We provide an overview about the current status of the data regarding BRCA1 deficiency and radiation therapy sensitivity in both experimental models and clinical investigations. In addition, we discuss a strategy to potentiate the effects of radiation therapy by poly(ADP-ribose) polymerase inhibitors, the pharmacologic drugs being investigated as monotherapy for the treatment of patients with BRCA1/2 mutations.

  7. Does selective logging stress tropical forest invertebrates? Using fat stores to examine sublethal responses in dung beetles.

    Science.gov (United States)

    França, Filipe; Barlow, Jos; Araújo, Bárbara; Louzada, Julio

    2016-12-01

    The increased global demand for tropical timber has driven vast expanses of tropical forests to be selectively logged worldwide. While logging impacts on wildlife are predicted to change species distribution and abundance, the underlying physiological responses are poorly understood. Although there is a growing consensus that selective logging impacts on natural populations start with individual stress-induced sublethal responses, this literature is dominated by investigations conducted with vertebrates from temperate zones. Moreover, the sublethal effects of human-induced forest disturbance on tropical invertebrates have never been examined. To help address this knowledge gap, we examined the body fat content and relative abundance of three dung beetle species (Coleoptera: Scarabaeinae) with minimum abundance of 40 individuals within each examined treatment level. These were sampled across 34 plots in a before-after control-impact design (BACI) in a timber concession area of the Brazilian Amazon. For the first time, we present evidence of logging-induced physiological stress responses in tropical invertebrates. Selective logging increased the individual levels of fat storage and reduced the relative abundance of two dung beetle species. Given this qualitative similarity, we support the measurement of body fat content as reliable biomarker to assess stress-induced sublethal effects on dung beetles. Understanding how environmental modification impacts the wildlife has never been more important. Our novel approach provides new insights into the mechanisms through which forest disturbances impose population-level impacts on tropical invertebrates.

  8. The Wiggle Index: An Open Source Bioassay to Assess Sub-Lethal Insecticide Response in Drosophila melanogaster.

    Science.gov (United States)

    Denecke, Shane; Nowell, Cameron J; Fournier-Level, Alexandre; Perry, Trent; Batterham, Phil

    2015-01-01

    Toxicological assays measuring mortality are routinely used to describe insecticide response, but sub-lethal exposures to insecticides can select for resistance and yield additional biological information describing the ways in which an insecticide impacts the insect. Here we present the Wiggle Index (WI), a high-throughput method to quantify insecticide response by measuring the reduction in motility during sub-lethal exposures in larvae of the vinegar fly Drosophila melanogaster. A susceptible wild type strain was exposed to the insecticides chlorantraniliprole, imidacloprid, spinosad, and ivermectin. Each insecticide reduced larval motility, but response times and profiles differed among insecticides. Two sets of target site mutants previously identified in mortality studies on the basis of imidacloprid or spinosad resistance phenotypes were tested. In each case the resistant mutant responded significantly less than the control. The WI was also able to detect a spinosad response in the absence of the primary spinosad target site. This response was not detected in mortality assays suggesting that spinosad, like many other insecticides, may have secondary targets affecting behaviour. The ability of the WI to detect changes in insecticide metabolism was confirmed by overexpressing the imidacloprid metabolizing Cyp6g1 gene in digestive tissues or the central nervous system. The data presented here validate the WI as an inexpensive, generic, sub-lethal assay that can complement information gained from mortality assays, extending our understanding of the genetic basis of insecticide response in D. melanogaster.

  9. Long-term impact of sublethal atrazine perturbs the redox homeostasis in pea (Pisum sativum L.) plants.

    Science.gov (United States)

    Ivanov, Sergei; Shopova, Elena; Kerchev, Pavel; Sergiev, Iskren; Miteva, Lyuba; Polizoev, Djovani; Alexieva, Vera

    2013-02-01

    Atrazine frequently contaminates soil, groundwater, rivers, and ponds. It is well know that acute doses (1-5 mM) of atrazine induce massive generation of singlet oxygen by blocking photosystem II. The sublethal concentrations of this herbicide, similar to those found in the environment, also reduce growth and disrupt photosynthesis in a long-term aspect, but exact mechanisms remain much uncertain. In this study the effects of environmentally relevant atrazine levels, ranging from 0.1 to 10 μM, on pea plants were characterized for up to 20 days. The plants exposed to continuous influence of atrazine exhibited perturbed redox homeostasis with increases of the lipid peroxides, the total and oxidized glutathione pools and elevated guaiacol peroxidase and glutathione-S-transferase activities. In contrast, the long-term atrazine impact did not affect superoxide dismutase activity whereas the catalase was inhibited. The perturbations of the redox status and the recruitment of the antioxidant machinery imply that the sublethal atrazine concentrations alter the poise between production and scavenging of reactive oxygen species. Taken together these results show that the long-term impact of sublethal atrazine has hallmarks of oxidative stress most probably triggered by generation of singlet oxygen.

  10. Sub-Lethal Dose of Shiga Toxin 2 from Enterohemorrhagic Escherichia coli Affects Balance and Cerebellar Cytoarchitecture

    Science.gov (United States)

    Pinto, Alipio; Cangelosi, Adriana; Geoghegan, Patricia A.; Tironi-Farinati, Carla; Brener, Gabriela J.; Goldstein, Jorge

    2016-01-01

    Shiga toxin producing Escherichia coli may damage the central nervous system before or concomitantly to manifested hemolytic–uremic syndrome symptoms. The cerebellum is frequently damaged during this syndrome, however, the deleterious effects of Shiga toxin 2 has never been integrally reported by ultrastructural, physiological and behavioral means. The aim of this study was to determine the cerebellar compromise after intravenous administration of a sub-lethal dose of Shiga toxin 2 by measuring the cerebellar blood–brain barrier permeability, behavioral task of cerebellar functionality (inclined plane test), and ultrastructural analysis (transmission electron microscope). Intravenous administration of vehicle (control group), sub-lethal dose of 0.5 and 1 ηg of Stx2 per mouse were tested for behavioral and ultrastructural studies. A set of three independent experiments were performed for each study (n = 6). Blood–brain barrier resulted damaged and consequently its permeability was significantly increased. Lower scores obtained in the inclined plane task denoted poor cerebellar functionality in comparison to their controls. The most significant lower score was obtained after 5 days of 1 ηg of toxin administration. Transmission electron microscope micrographs from the Stx2-treated groups showed neurons with a progressive neurodegenerative condition in a dose dependent manner. As sub-lethal intravenous Shiga toxin 2 altered the blood brain barrier permeability in the cerebellum the toxin penetrated the cerebellar parenchyma and produced cell damaged with significant functional implications in the test balance. PMID:26904009

  11. Performance of honey bee colonies under a long-lasting dietary exposure to sublethal concentrations of the neonicotinoid insecticide thiacloprid.

    Science.gov (United States)

    Siede, Reinhold; Faust, Lena; Meixner, Marina D; Maus, Christian; Grünewald, Bernd; Büchler, Ralph

    2017-07-01

    Substantial honey bee colony losses have occurred periodically in the last decades. The drivers for these losses are not fully understood. The influence of pests and pathogens are beyond dispute, but in addition, chronic exposure to sublethal concentrations of pesticides has been suggested to affect the performance of honey bee colonies. This study aims to elucidate the potential effects of a chronic exposure to sublethal concentrations (one realistic worst-case concentration) of the neonicotinoid thiacloprid to honey bee colonies in a three year replicated colony feeding study. Thiacloprid did not significantly affect the colony strength. No differences between treatment and control were observed for the mortality of bees, the infestation with the parasitic mite Varroa destructor and the infection levels of viruses. No colony losses occurred during the overwintering seasons. Furthermore, thiacloprid did not influence the constitutive expression of the immunity-related hymenoptaecin gene. However, upregulation of hymenoptaecin expression as a response to bacterial challenge was less pronounced in exposed bees than in control bees. Under field conditions, bee colonies are not adversely affected by a long-lasting exposure to sublethal concentrations of thiacloprid. No indications were found that field-realistic and higher doses exerted a biologically significant effect on colony performance. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

  12. Life table study of the effects of sublethal concentrations of thiamethoxam on Bradysia odoriphaga Yang and Zhang.

    Science.gov (United States)

    Zhang, Peng; Liu, Feng; Mu, Wei; Wang, Qiuhong; Li, Hui; Chen, Chengyu

    2014-05-01

    Bradysia odoriphaga Yang and Zhang (chive gnat) is the major insect pest affecting Chinese chive in Northern China. In order to explore the integrated control of B. odoriphaga, sublethal effects of the neonicotinoid insecticide thiamethoxam were studied. The standard contact and stomach bioassay method was used to assess the effects of sublethal (LC5 and LC20) concentrations of thiamethoxam on the demographic parameters of B. odoriphaga, and data were interpreted based on the age-stage, two-sex life table theory. After thiamethoxam treatment, the intrinsic and finite rates of increase, net reproduction rate, survival rate, and reproductive value were all markedly decreased, while the mean generation time, total preovipositional period, and larval and pupal duration were prolonged, compared with controls. The intrinsic rates of increase dropped from 0.1775/day to 0.1502-0.1136/day. Following LC5 and LC20 treatments, net reproduction rate dropped from 61.75 offspring/individual (control) to 43.36 and 20.75 offspring/individual, respectively. Sublethal concentrations of thiamethoxam decreased the developmental rate of laboratory populations of B. odoriphaga, suggesting that such doses may be useful in integrated pest management strategies.

  13. Sublethal effects of imidacloprid on the fecundity, longevity, and enzyme activity of Sitobion avenae (Fabricius) and Rhopalosiphum padi (Linnaeus).

    Science.gov (United States)

    Lu, Y-H; Zheng, X-S; Gao, X-W

    2016-08-01

    The aphid species Sitobion avenae and Rhopalosiphum padi are the most important pests in wheat growing regions of many countries. In this study, we investigated the sublethal effects of imidacloprid on fecundity, longevity, and enzyme activity in both aphid species by comparing 3-h exposure for one or three generations. Our results indicated that 3-h exposure to sublethal doses of imidacloprid for one generation had no discernible effect on the survival, fecundity, longevity, or enzyme activity levels of aphids. However, when pulse exposures to imidacloprid were sustained over three generations, both fecundity and longevity were significantly decreased in both S. avenae and R. padi. Interestingly, the fecundity of R. padi had almost recovered by the F5 generation, but its longevity was still deleteriously affected. These results indicated that R. padi laid eggs in shorter time lags and has a more fast resilience. The change in reproduction behavior may be a phenomenon of R. padi to compensate its early death. If this is stable for the next generation, it means that the next generation is more competitive than unexposed populations, which could be the reason underlying population outbreaks that occur after longer-term exposure to an insecticide. This laboratory-based study highlights the sublethal effects of imidacloprid on the longevity and fecundity of descendants and provides an empirical basis from which to consider management decisions for chemical control in the field.

  14. {sup 1}H NMR metabolomics of earthworm exposure to sub-lethal concentrations of phenanthrene in soil

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Sarah A.E.; McKelvie, Jennifer R.; Simpson, Andre J. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, Ontario, M1C 1A4 (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.c [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, Ontario, M1C 1A4 (Canada)

    2010-06-15

    {sup 1}H NMR metabolomics was used to monitor earthworm responses to sub-lethal (50-1500 mg/kg) phenanthrene exposure in soil. Total phenanthrene was analyzed via soxhlet extraction, bioavailable phenanthrene was estimated by hydroxypropyl-beta-cyclodextrin (HPCD) and 1-butanol extractions and sorption to soil was assessed by batch equilibration. Bioavailable phenanthrene (HPCD-extracted) comprised approx65-97% of total phenanthrene added to the soil. Principal component analysis (PCA) showed differences in responses between exposed earthworms and controls after 48 h exposure. The metabolites that varied with exposure included amino acids (isoleucine, alanine and glutamine) and maltose. PLS models indicated that earthworm response is positively correlated to both total phenanthrene concentration and bioavailable (HPCD-extracted) phenanthrene in a freshly spiked, unaged soil. These results show that metabolomics is a powerful, direct technique that may be used to monitor contaminant bioavailability and toxicity of sub-lethal concentrations of contaminants in the environment. These initial findings warrant further metabolomic studies with aged contaminated soils. - {sup 1}H NMR metabolomics is used to directly monitor metabolic responses of Eisenia fetida after 48 h of exposure to sub-lethal concentrations of phenanthrene in soil.

  15. The Wiggle Index: An Open Source Bioassay to Assess Sub-Lethal Insecticide Response in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Shane Denecke

    Full Text Available Toxicological assays measuring mortality are routinely used to describe insecticide response, but sub-lethal exposures to insecticides can select for resistance and yield additional biological information describing the ways in which an insecticide impacts the insect. Here we present the Wiggle Index (WI, a high-throughput method to quantify insecticide response by measuring the reduction in motility during sub-lethal exposures in larvae of the vinegar fly Drosophila melanogaster. A susceptible wild type strain was exposed to the insecticides chlorantraniliprole, imidacloprid, spinosad, and ivermectin. Each insecticide reduced larval motility, but response times and profiles differed among insecticides. Two sets of target site mutants previously identified in mortality studies on the basis of imidacloprid or spinosad resistance phenotypes were tested. In each case the resistant mutant responded significantly less than the control. The WI was also able to detect a spinosad response in the absence of the primary spinosad target site. This response was not detected in mortality assays suggesting that spinosad, like many other insecticides, may have secondary targets affecting behaviour. The ability of the WI to detect changes in insecticide metabolism was confirmed by overexpressing the imidacloprid metabolizing Cyp6g1 gene in digestive tissues or the central nervous system. The data presented here validate the WI as an inexpensive, generic, sub-lethal assay that can complement information gained from mortality assays, extending our understanding of the genetic basis of insecticide response in D. melanogaster.

  16. Sub-Lethal Dose of Shiga toxin 2 from Enterohemorrhagic Escherichia coli Affects Balance and Cerebellar Cythoarquitecture.

    Directory of Open Access Journals (Sweden)

    Luciana eD’Alessio

    2016-02-01

    Full Text Available Shiga toxin producing Escherichia coli may damage the central nervous system before or concomitantly to manifested hemolytic uremic syndrome symptoms. The cerebellum is frequently damaged during this syndrome, however the deleterious effects of Shiga toxin 2 has never been integrally reported by ultrastructural, physiological and behavioral means. The aim of this study was to determine the cerebellar compromise after intravenous administration of a sub-lethal dose of Shiga toxin 2 by measuring the cerebellar blood brain barrier permeability, behavioral task of cerebellar functionality (inclined plane test, and ultrastructural analysis (transmission electron microscope. Intravenous administration of vehicle (control group, sub-lethal dose of 0.5 ηg and 1 ηg of Stx2 per mouse were tested for behavioral and ultrastructural studies. A set of three independent experiments were performed for each study (n=6. Blood–Brain Barrier resulted damaged and consequently its permeability was significantly increased. Lower scores obtained in the inclined plane task denoted poor cerebellar functionality in comparison to their controls. The most significant lower score was obtained after 5 days of 1ηg of toxin administration. Transmission electron microscope micrographs from the Stx2-treated groups showed neurons with a progressive neurodegenerative condition in a dose dependent manner. As sub-lethal intravenous Shiga toxin 2 altered the blood brain barrier permeability in the cerebellum the toxin penetrated the cerebellar parenchyma and produced cell damaged with significant functional implications in the test balance.

  17. Influence of sub-lethal stresses on the survival of lactic acid bacteria after spray-drying in orange juice.

    Science.gov (United States)

    Barbosa, J; Borges, S; Teixeira, P

    2015-12-01

    The demand for new functional non-dairy based products makes the production of a probiotic orange juice powder an encouraging challenge. However, during drying process and storage, loss of viability of the dried probiotic cultures can occur, since the cells are exposed to various stresses. The influence of sub-lethal conditions of temperature, acidic pH and hydrogen peroxide on the viability of Pediococcus acidilactici HA-6111-2 and Lactobacillus plantarum 299v during spray drying in orange juice and subsequent storage under different conditions was investigated. At the end of storage, the survival of both microorganisms through simulated gastro-intestinal tract (GIT) conditions was also determined. The viability of cells previously exposed to each stress was not affected by the drying process. However, during 180 days of storage at room temperature, unlike P. acidilactici HA-6111-2, survival of L. plantarum 299v was enhanced by prior exposure to sub-lethal conditions. Previous exposure to sub-lethal stresses of each microorganism did not improve their viability after passage through simulated GIT. Nevertheless, as cellular inactivation during 180 days of storage was low, both microorganisms were present in numbers of ca. 10(7) cfu/mL at the end of GIT. This is an indication that both bacteria are good candidates for use in the development of an orange juice powder with functional characteristics.

  18. Mediator MED23 Links Pigmentation and DNA Repair through the Transcription Factor MITF

    Directory of Open Access Journals (Sweden)

    Min Xia

    2017-08-01

    Full Text Available DNA repair is related to many physiological and pathological processes, including pigmentation. Little is known about the role of the transcriptional cofactor Mediator complex in DNA repair and pigmentation. Here, we demonstrate that Mediator MED23 plays an important role in coupling UV-induced DNA repair to pigmentation. The loss of Med23 specifically impairs the pigmentation process in melanocyte-lineage cells and in zebrafish. Med23 deficiency leads to enhanced nucleotide excision repair (NER and less DNA damage following UV radiation because of the enhanced expression and recruitment of NER factors to chromatin for genomic stability. Integrative analyses of melanoma cells reveal that MED23 controls the expression of a melanocyte master regulator, Mitf, by modulating its distal enhancer activity, leading to opposing effects on pigmentation and DNA repair. Collectively, the Mediator MED23/MITF axis connects DNA repair to pigmentation, thus providing molecular insights into the DNA damage response and skin-related diseases.

  19. Radiation Protection

    Science.gov (United States)

    ... EPA United States Environmental Protection Agency Search Search Radiation Protection Share Facebook Twitter Google+ Pinterest Contact Us Radiation Protection Document Library View and download EPA radiation ...

  20. DNA Repair-Protein Relocalization After Heavy Ion Exposure

    Science.gov (United States)

    Metting, N. F.

    1999-01-01

    Ionizing radiation is good at making DNA double strand breaks, and high linear energy transfer (LET) radiations such as heavy ion particles are particularly efficient. For this reason, the proteins belonging to repair systems that deal with double strand breaks are of particular interest. One such protein is Ku, a component in the non-homologous recombination repair system. The Ku protein is an abundant, heterodimeric DNA end-binding complex, composed of one 70 and one 86 kDa subunit. Ku protein binds to DNA ends, nicks, gaps, and regions of transition between single and double-stranded structure. These binding properties suggest an important role in DNA repair. The Ku antigen is important in this study because it is present in relatively large copy numbers and it is part of a double-strand-break repair system. More importantly, we consistently measure an apparent upregulation in situ that is not verified by whole-cell-lysate immunoblot measurements. This apparent upregulation is triggered by very low doses of radiation, thus showing a potentially useful high sensitivity. However, elucidation of the mechanism underlying this phenomenon is still to be done.

  1. UV exposed electronically activated damage and photoreactivation repair

    Science.gov (United States)

    Bohr, Henrik; Malik, Bary

    2007-03-01

    An investigation of the possible physics underlying the damage caused to DNA by UV radiation and its subsequent repair via a photoreactivation mechanism is presented in this study. An electronic pathway starting from the initial damage to the final repair process is proposed. UV radiation is absorbed to create a hole-excited thymine or other pyrimidine that subsequently is responsible for the formation of the thymine dimer. The negative-ion of the cofactor riboflavin, FADH-, formed by the exposure of the photolyase protein to visible light interacts with the hole-excited electronic orbital of the thymine dimer inducing a photon-less Auger transition, which restores the two thymines to the ground state, thereby detaching the lesion and repairing the DNA. Due to energy balance, the process has to involve an electronic excited state (s). The mechanism involves the least amount of energy dissipation and is charge neutral. It also avoids radiation damage in the repair process, that is, is a radiationless process.

  2. Acute lethal and behavioral sublethal responses of two stored-product psocids to surface insecticides.

    Science.gov (United States)

    Guedes, Raul Narciso C; Campbell, James F; Arthur, Frank H; Opit, George P; Zhu, Kun Yan; Throne, James E

    2008-12-01

    The psocids Liposcelis bostrychophila Badonnel and L. entomophila (Enderlein) (Liposcelididae) are emerging pests of stored products. Although their behavior, particularly their high mobility, may contribute to the reported relatively low efficacy of insecticides against them, studies to investigate this have not been conducted. The present study aimed to assess the label rate efficacy of three commercial insecticides (beta-cyfluthrin, chlorfenapyr and pyrethrins) applied on concrete surfaces against L. bostrychophila and L. entomophila, and also their sublethal effect on the mobility of these species. The synthetic insecticides beta-cyfluthrin and chlorfenapyr showed high short-term efficacy (LT(95)or= 4 days). Liposcelis bostrychophila was slightly more tolerant (>or=1.2x) than L. entomophila to all three insecticides. Behavioral assays with fully sprayed and half-sprayed concrete arenas indicated that the insecticides reduced the mobility of both species. Pyrethrins seem to elicit weak repellence in L. bostrychophila. beta-Cyfluthrin and chlorfenapyr were effective against both psocid species, but not pyrethrins. The mobility of both species does not seem to play a major role in the differential selectivity observed, but the lower mobility of L. bostrychophila may be a contributing factor to its higher insecticide tolerance.

  3. Induced tolerance from a sublethal insecticide leads to cross-tolerance to other insecticides.

    Science.gov (United States)

    Hua, Jessica; Jones, Devin K; Relyea, Rick A

    2014-04-01

    As global pesticide use increases, the ability to rapidly respond to pesticides by increasing tolerance has important implications for the persistence of nontarget organisms. A recent study of larval amphibians discovered that increased tolerance can be induced by an early exposure to low concentrations of a pesticide. Since natural systems are often exposed to a variety of pesticides that vary in mode of action, we need to know whether the induction of increased tolerance to one pesticide confers increased tolerance to other pesticides. Using larval wood frogs (Lithobates sylvaticus), we investigated whether induction of increased tolerance to the insecticide carbaryl (AChE-inhibitor) can induce increased tolerance to other insecticides that have the same mode of action (chlorpyrifos, malathion) or a different mode of action (Na(+)channel-interfering insecticides; permethrin, cypermethrin). We found that embryonic exposure to sublethal concentrations of carbaryl induced higher tolerance to carbaryl and increased cross-tolerance to malathion and cypermethrin but not to chlorpyrifos or permethrin. In one case, the embryonic exposure to carbaryl induced tolerance in a nonlinear pattern (hormesis). These results demonstrate that that the newly discovered phenomenon of induced tolerance also provides induced cross-tolerance that is not restricted to pesticides with the same mode of action.

  4. Assessment of Mercury Bioaccumulation in Zebra Cichlid (Cichlasoma Nigrofasciatum Exposed to Sublethal Concentrations of Permethrin

    Directory of Open Access Journals (Sweden)

    Mahdi Banaee

    2014-12-01

    Full Text Available Background: Aquatic ecosystems are frequently subjected to contamination by toxic heavy metals and pesticides, yet very little is known about the influence of pesticides on bioaccumulation of heavy metals in aquatic organisms. Mercury is a toxic metal with no known biological benefit to organisms. Bioavailability of mercury in aquatic environments depends on biological and non-biological parameters including other pollutants. Therefore, the objectives of this research were to determine the effects of permethrin on bioaccumulation of mercury in zebra cichlid. Methods: Acute toxicity (LC50 of permethrin and mercury chloride was evaluated by estimating mortality in Probit Model in SPSS (version 19.0 IBM. In sub-lethal toxicity, zebra cichlid (Cichlasoma nigrofasciatum was exposed to various concentrations of permethrin (0.0, 0.40, 0.80, 1.20 and 1.60 µg.L-1 combined with 20 µg.L-1 mercury chloride for 15 days. At the end of the experiment, mercury concentrations were measured using ICP-OES-Perkin elmer (optima 7300-DV. Results: 96 h LC50 values of permethrin and mercury for C. nigrofasciatum were calculated to be 17.55 µg.L-1 and 140.38 µg.L-1, respectively. Our results clearly showed that the bioaccumulation of mercury in the specimens increased with increasing concentrations of permethrin to 1.20 and 1.60 µg.L-1. Conclusion: Increasing the concentration of permethrin had synergistic effects on the bioaccumulation of mercury in fish.

  5. Inhibition of acetylcholinesterase in guppies (Poecilia reticulata) by chlorpyrifos at sublethal concentrations: Methodological aspects

    Energy Technology Data Exchange (ETDEWEB)

    van der Wel, H.; Welling, W.

    1989-04-01

    Acetylcholinesterase activity is a potential biochemical indicator of toxic stress in fish and a sensitive parameter for testing water for the presence of organophosphates. A number of methodological aspects regarding the determination of the in vivo effect of chlorpyrifos on acetylcholinesterase in guppies have been investigated. It was found that with acetylthiocholine as a substrate, the contribution of pseudocholinesterase to the total cholinesterase activity can be neglected. Protection of acetylcholinesterase of guppies exposed to chlorpyrifos from additional, artifactual in vitro enzyme inhibition during homogenization is necessary. Very low concentrations of acetone in the exposure medium, resulting from dilution of the stock solution of chlorpyrifos in acetone, can result in large decreases in the oxygen content of this medium. This may affect the uptake rate of the toxic compound and, thereby, cholinesterase inhibition. Very low, sublethal concentrations of chlorpyrifos result in high inhibition levels of acetylcholinesterase (80-90%) in guppies within 2 weeks of continuous exposure. Recovery of the enzyme activity occurs after the exposed animals are kept in clean medium for 4 days, but the rate of recovery is considerably lower than the rate of inhibition.

  6. Haematological changes in Bufo maculatus treated with sublethal concentrations of Cadmium

    Directory of Open Access Journals (Sweden)

    Lawrence Ikechukwu Ezemonye

    2011-12-01

    Full Text Available Adult Bufo maculatus was exposed to sublethal cadmium concentrations of 0.25, 0.50, 1.00 and 2.00 mg/L. The toxicant from which the cadmium concentrations were prepared was cadmium chloride (CdCl2.H2O. There were three replicate tanks per treatment and three individuals per tank including control groups. The hematologic alterations based on the examination of blood indices during the 28 days of exposure showed that total erythrocyte count (TEC, hematocrit (Hct and hemoglobin (Hb concentration decreased (P<0.05 relative to controls. The decline was concentration- dependent as concentration of cadmium increased. The decline in hemoglobin and hematocrit in the experimental organism could be due to a decrease in the synthesis or release of erythrocytes into the circulation or an increase in the rate of erythrocyte destruction inflicted by cadmium toxicity. There was significant (P<0.05 elevation in total leuko- leukocyte count (TLC with increase in the concen- cyte concentration of cadmium. The increase in total leukocyte count observed in this study could be attributed to a stimulation of the immune system in response to tissue damage caused by cadmium toxicity. The study has shown that the exposure of the Bufo maculatus toad to cadmium can inflict alterations in the hematologic indices, which could induce unfavorable physiological changes in the amphibian, which may lead to death. There is, therefore, the need to protect amphibians in order to sustain the biodiversity in the Nigerian Niger Delta ecological zone.

  7. Sublethal Effects of Methanolic Extract of Raphia hookeri on the Reproductive Capacity of Clarias gariepinus

    Directory of Open Access Journals (Sweden)

    Adedotun O. Afolayan

    2014-01-01

    Full Text Available Raphia hookeri fruits are used for fishing in Nigeria due to their ichthyotoxic properties. This study investigated the toxic effects of R. hookeri on the reproductive capacity of Clarias gariepinus. The results from both short-term (96-hour test and long-term (3-month sublethal test bioassays revealed a linear relationship between R. hookeri extract dose and negative effects on the catfish. The percentage survival of both sexes of the catfish decreased with increasing extract concentration at short-term exposure, with LC50 values of 600 mg/L and 800 mg/L for male and female, respectively. At long-term exposure, the reproductive capacity of 10–12-month-old male and female brood-stocks diminished at relatively higher concentrations of R. hookeri fruit extract, with the gravid females producing fewer and mostly unviable eggs. The fruit extract also affected the eggs’ hatchability and fry survival when the exposed gravid females were treated with pituitary hormone and sperms from unexposed males, while the exposed males were unable to sexually stimulate female brooders. Sperms and pituitary hormone from exposed males were infertile, leading to low percentage of hatched eggs and mortality of the few hatched fries within 24 hours. These results confirmed the ethnobotanical use of this fruit extract for fishing in Nigeria.

  8. Zinc-related actions of sublethal levels of benzalkonium chloride: Potentiation of benzalkonium cytotoxicity by zinc.

    Science.gov (United States)

    Mitani, Tsuyoshi; Elmarhomy, Ahmed Ibrahim Elhossany; Dulamjav, Luvsandorj; Anu, Enkhtumur; Saitoh, Shohei; Ishida, Shiro; Oyama, Yasuo

    2017-04-25

    Benzalkonium chloride (BZK) is a common preservative used in pharmaceutical and personal care products. ZnCl2 was recently reported to significantly potentiate the cytotoxicity of some biocidal compounds. In the present study, therefore, we compared the cytotoxic potency of BZK and then further studied the Zn(2+)-related actions of the most cytotoxic agent among BZK, using flow cytometric techniques with appropriate fluorescent probes in rat thymocytes. Cytotoxicity of benzylcetyldimethylammonium (BZK-C16) was more potent that those of benzyldodecyldimethylammonium and benzyldimethyltetradecylammonium. ZnCl2 (1-10 μM) significantly potentiated the cytotoxicity of BZK-C16 at a sublethal concentration (1 μM). The co-treatment of cells with 3 μM ZnCl2 and 1 μM BZK-C16 increased the population of both living cells with phosphatidylserine exposed on membrane surfaces and dead cells. BZK-C16 at 0.3-1.0 μM elevated intracellular Zn(2+) levels by increasing Zn(2+) influx, and augmented the cytotoxicity of 100 μM H2O2. Zn(2+) is concluded to facilitate the toxicity of BZK. We suggest that the toxicity of BZK is determined after taking extracellular (plasma) and/or environmental Zn(2+) levels into account.

  9. A sublethal imidacloprid concentration alters foraging and competition behaviour of ants.

    Science.gov (United States)

    Thiel, Sarina; Köhler, Heinz-R

    2016-05-01

    Neonicotinoid pesticides, such as the widely used compound imidacloprid, are suspected to impair cognitive capacity, behaviour, and fitness of a number of non-target species. We tested whether sublethal imidacloprid concentrations alter the foraging and aggression behaviour of two European ant species. Even though the nestmate-recruitment of Lasius niger was not affected by pesticide exposure, these ants required more time to become active and the number of foraging workers was lower than in sub-colonies not exposed to imidacloprid. In interspecific confrontations, imidacloprid increased the aggressiveness of a usually subordinate species (Lasius flavus) enormously (3.7-fold increase in average number of aggressive encounters), whereas they did not affect a subdominant species (L. niger) that severely (1.2-fold increase in average number of aggressive encounters). The high frequency of aggressive encounters of L. flavus vs. non-exposed L. niger workers, reduced their survival probability significantly down to 60 %. The observed behavioural alterations of the two ant species have the potential to impair their viability and co-occurrence with behaviourally dominate species due to a decreased exploitative competition and a reduced chance to locate and use resources before competitors. As competition is considered key in structuring ant communities, changes in aggressiveness are likely to alter established dominance hierarchies and thereby the dynamic and structure of ant communities.

  10. Sublethal Effects in Pest Management: A Surrogate Species Perspective on Fruit Fly Control

    Directory of Open Access Journals (Sweden)

    John E. Banks

    2017-07-01

    Full Text Available Tephritid fruit flies are economically important orchard pests globally. While much effort has focused on controlling individual species with a combination of pesticides and biological control, less attention has been paid to managing assemblages of species. Although several tephritid species may co-occur in orchards/cultivated areas, especially in mixed-cropping schemes, their responses to pesticides may be highly variable. Furthermore, predictive efforts about toxicant effects are generally based on acute toxicity, with little or no regard to long-term population effects. Using a simple matrix model parameterized with life history data, we quantified the responses of several tephritid species to the sublethal effects of a toxicant acting on fecundity. Using a critical threshold to determine levels of fecundity reduction below which species are driven to local extinction, we determined that threshold levels vary widely for the three tephritid species. In particular, Bactrocera dorsalis was the most robust of the three species, followed by Ceratitis capitata, and then B. cucurbitae, suggesting individual species responses should be taken into account when planning for area-wide pest control. The rank-order of susceptibility contrasts with results from several field/lab studies testing the same species, suggesting that considering a combination of life history traits and individual species susceptibility is necessary for understanding population responses of species assemblages to toxicant exposure.

  11. Decreased survival of rainbow trout exposed to no. 2 fuel oil caused by sublethal preexposure

    Science.gov (United States)

    Steadman, B. L.; Stubblefield, W. A.; Lapoint, T. W.; Bergman, H.L.; Kaiser, M.S.

    1991-01-01

    Rainbow trout (Oncorhynchus mykiss) were exposed for 21 d to sublethal levels of No. 2 fuel oil (2FO). The four exposure concentrations ranged from 12 to 100 mg/L 2FO dispersed in water and resulted in 0 to 12% mortality. Following this exposure period (preexposure) the ability of preexposed trout to survive exposure to acutely lethal levels of 2FO was observed. Preexposure to either 50 or 100 mg/L 2FO consistently resulted in decreased survival and a lower LC50 for a given observation period. Unfortunately, because the LC50 determinations were not obtained independently, they could not be used to test statistically the effects of preexposure on survival. Therefore, two proportional hazard modeling techniques were applied to the data to test for effects due to preexposure. Both modeling techniques indicated that preexposure results in decreased survival of rainbow trout exposed to acutely toxic levels of 2FO. Thus, in contrast to preexposure to metals, which results in acclimation, preexposure to 2FO results in decreased survival.

  12. Toxicity assessment of sodium fluoride in Drosophila melanogaster after chronic sub-lethal exposure.

    Science.gov (United States)

    Dutta, Moumita; Rajak, Prem; Khatun, Salma; Roy, Sumedha

    2017-01-01

    Sodium fluoride (NaF), one of the most frequently used fluoride compound is composed of Na(+) and F(-). Apart from its use in water fluoridation, NaF also acts as a major component for different dental products like toothpastes, gels and mouth rinses etc. The present study was carried out to explore the toxic impact of chronic NaF exposure on a non-target organism, Drosophila melanogaster. The larvae exposed to different concentrations of NaF through food showed a significant increase in HSP70 expression both qualitatively and quantitatively. The altered tail length and tail intensity in Comet assay validate the increased DNA damage in treated larvae. The activity of AChE, oxidative stress marker enzymes, phase I and phase II detoxifying enzymes were found to be significantly inhibited in the treated larvae when compared to control though there was no evidence of dose dependent change in each case. The alterations in the mentioned parameters can be due to increased body Fluoride ion (F(-)) concentration since the analysis with ion electrode analyzer revealed that F(-) concentration increased significantly with NaF treatment. Hence, the results suggest that D. melanogaster manifest prominent toxic response when subjected to chronic exposure to sub-lethal NaF concentrations.

  13. Cadmium accumulation and biochemical responses in Sparus aurata following sub-lethal Cd exposure.

    Science.gov (United States)

    Isani, G; Andreani, G; Cocchioni, F; Fedeli, D; Carpené, E; Falcioni, G

    2009-01-01

    Cadmium (Cd), a heavy metal with limited biological function, is widely distributed in the aquatic environment as a result of natural and anthropogenic activities. The effect of 4 and 11 days exposure of gilthead sea bream Sparus aurata to sub-lethal concentrations of Cd was evaluated as levels of Cd content and Cd-metallothionein (MT) presence in different organs. The possible genotoxic effect was also evaluated in erythrocytes by using the "comet assay", a promising tool for estimating DNA damage at the single-cell level. The results obtained show that in the controls, Cd content was significantly higher in gills compared to in liver, but the treatment of fish with 0.1mg/l Cd induced a stronger accumulation of metal in liver depending on the length of the exposure period. Cd traces were found in plasma, muscle and kidney. Cd forms complexes in the cytosol with MT only in the liver but Cd-MT content significantly increased after 11 days of exposure to the metal, while after 4 days of treatment the protein level was similar to the control. The "comet assay" performed on S. aurata eryhtrocytes isolated from fish treated for 4 and 11 days with 0.1mg/l Cd, showed that there was no DNA damage at both exposure periods.

  14. Sublethal toxicity of orchard stormwater runoff in Sacramento splittail (Pogonichthys macrolepidotus) larvae.

    Science.gov (United States)

    Teh, Swee J; Deng, DongFang; Werner, Inge; Teh, FooChing; Hung, Silas S O

    2005-04-01

    The sublethal effects of stormwater runoff from sections of a plum orchard treated with esfenvalerate or diazinon were evaluated in 7-day-old Sacramento splittail (Pogonichthys macrolepidotus) larvae. Fish were exposed to eight runoff samples using the USEPA standard static renewal method for 96 h acute toxicity testing, then transferred to clean water for three-month to assess the survival, growth, histopathological abnormalities, and heat stress proteins (hsp). No significant mortality was observed at 96 h in exposed fish. At one week, histopathological abnormalities included severe glycogen depletion, cytoplasmic protein droplets, vacuolar degeneration, and cell necroses in liver of all exposure groups. Pyknotic nerve cells were seen in brain of one exposure group. Significantly higher cumulative mortality, lower condition factor, and elevated hsp60 and hsp70 levels (p < 0.05) were occurred in several exposure groups. No histopathological abnormalities were observed after three months in any exposure group. This study confirms that standard acute toxicity tests have underestimated the toxicity of stormwater runoff, and although splittail larvae survived the 96 h exposure, they exhibited reduced survival and growth and showed signs of cellular stress even after a three month recovery period.

  15. The effect of sublethal short-duration exposure of paraoxon on pregnancy and fetuses in mice

    Directory of Open Access Journals (Sweden)

    Nurulain Syed M.

    2015-01-01

    Full Text Available A convincing number of epidemiological studies have reported on the exposure to and consequences of organophosphorus compounds (OPCs in pregnant women. However, there is still a knowledge gap and paucity of systematic literature from animal studies. This study was undertaken with the hypothesis that short-duration sublethal exposure to OPCs can produce maternal and fetal lethal effects as chronic exposure. This study examineses the teratogenicity and embryotoxicity of paraoxon (POX in mice at a dose that is non-lethal to non-pregnant mothers. Pregnant mice were injected intraperitoneally (i.p. with paraoxon (50 nmol/mouse on the 4th and 5th days of gestation, and the effect of the treatment was assessed on day 18 of gestation. This dose was fatal to pregnant mice in 21% of instances as compared to non-pregnant animals in which 0% mortality was detected, even after daily injection of a similar dose for five days. Significant inhibition of red blood cell acetylcholinesterase (RBC-AChE was observed in pregnant mice as compared to non-pregnant ones; however, no apparent neuronal effect was detected. Of note were fetal weight decrement, pregnancy termination, intrauterine growth retardation and maternal death. We concluded that exposure to even a non-toxic dose might be critical for pregnant mothers, the pregnancy as well as fetuses. In addition, even exposure of short duration can be detrimental and capable of producing profound and fatal effects.

  16. Enzymatic Alterations and Genotoxic Effects Produced by Sublethal Concentrations of Organophosphorous Temephos in Poecilia reticulata.

    Science.gov (United States)

    Pereira, Boscolli Barbosa; de Campos Júnior, Edimar Olegário

    2015-01-01

    The responses of biochemical and genetic parameters were evaluated in tissues of Poecilia reticulata exposed to sublethal and environmentally relevant concentrations of 0.005, 0.01, or 0.02 mg/L of the organophosphorous (OP) pesticide temephos (TE) for 168 h. Activities of enzymes brain acetylcholinesterase (AChE) and liver carboxylesterase (CbE) were determined. Nuclear abnormalities (NA) and micronucleus (MN) frequency in gill erythrocytes were also measured. No mortality was observed over the experimental period; however, brain AChE activities were decreased significantly in guppies in all TE treatment groups after 72 h of exposure. Hepatic CbE activities of fish were increased in all TE treatment groups at 96, 120, and 144 h of exposure. The frequencies of MN and NA in fish gill erythrocytes displayed a marked rise after 168 h of exposure to concentrations of 0.01 or 0.02 mg/L TE. Thus, determination of these parameters may be employed as potential indices of exposure to TE using this sentinel organism for monitorining.

  17. Inducible repair of oxidative DNA damage in Escherichia coli.

    Science.gov (United States)

    Demple, B; Halbrook, J

    Hydrogen peroxide is lethal to many cell types, including the bacterium Escherichia coli. Peroxides yield transient radical species that can damage DNA and cause mutations. Such partially reduced oxygen species are occasionally released during cellular respiration and are generated by lethal and mutagenic ionizing radiation. Because cells live in an environment where the threat of oxidative DNA damage is continual, cellular mechanisms may have evolved to avoid and repair this damage. Enzymes are known which evidently perform these functions. We report here that resistance to hydrogen peroxide toxicity can be induced in E. coli, that this novel induction is specific and occurs, in part, at the level of DNA repair.

  18. Signalization and repair of the DNA double-strand breaks of in the cerebral tumors: modulation of the radiation response with the chemotherapy treatments; Signalization et reparation des cassures double-brin de l'ADN dans les gliomes: modulation de la reponse aux traitements chimio-radiotherapeutiques

    Energy Technology Data Exchange (ETDEWEB)

    Marcinkova-Bencokova, Z

    2007-07-15

    There are about 6000 new cases of nervous system tumours each year in France. However, the current radio chemotherapeutic approaches against brain tumours remain still insufficient to produce a satisfactory therapeutic index. In parallel, the knowledge of the early radiobiological events has considerably progressed in the last few years. This thesis aims to provide new insights in the molecular and cellular response of brain tumours to radio chemotherapy. This thesis was divided into four stages. Stage 1: a novel DNA double-strand breaks repair pathway depending on the MRE11 protein but independent of the phosphorylation of H2AX emerged from the study of artefacts of the immunofluorescence technique and a systematic analysis of the radiosensitivity of human cells. Stage 2: the radiobiological features of 3 rodent models of glioma among the most used in preclinical trials and of 7 human glioma cell lines were investigated. Functional impairments of the BRCA1 protein in response to radiation and/or cisplatin were observed in the majority of the models tested, raising the question of the role of this protein in the anti-glioma treatments and in glioma genesis. Stage 3: in order to extend our approach to genetic syndromes associated with cerebral tumours predisposition, the radiobiological characteristics of the fibroblasts resulting from patients suffering from neurofibromatosis type 1 (NF1), a pathology associated with a strong incidence of peripheral nervous system tumours, were investigated. NF1 appeared to be a syndrome with moderated radiosensitivity, associated with a weak deficiency of DNA end-joining repair but with a strong activity of MRE11. These results enabled us to propose a preliminary model involving both proteins BRCA1 and NF1. Stage 4: considering the role of BRCA1 in the inhibition of some tyrosine kinase activity and in the response to cisplatin, we tested the radiobiological effects of treatments combining radiation, cisplatin and tyrosine kinase

  19. Radiation Therapy

    Science.gov (United States)

    ... the area is stitched shut. Another treatment, called proton-beam radiation therapy , focuses the radiation on the ... after radiation treatment ends. Sore mouth and tooth decay. If you received radiation therapy to the head ...

  20. Radiation sickness

    Science.gov (United States)

    ... radiation. There are two basic types of radiation: ionizing and nonionizing. Nonionizing radiation comes in the form of light, radio waves, microwaves and radar. This kind of radiation usually ...

  1. Sensitizing Osteosarcoma to Radiation Therapy

    Science.gov (United States)

    Mamo, Tewodros Kebede

    Several strategies to enhance the effects of radiation therapy are being explored for various cancers, with multiple molecular pathways and physical approaches suggested to play a role. One approach to improve the effectiveness of radiation therapy in tumors is the use of radiosensitizing molecules. Among the key radiosensitizing molecules being explored in various cancers include pharmacologic inhibitors of DNA repair and gold nanoparticles that physically enhance the amount of radiation deposited inside cancer cells. The main goal of this thesis is to explore the role of DNA repair inhibition as a radiosensitizing strategy for osteosarcoma cells. Additionally, the thesis investigates the effects of particle size in the application of gold nanoparticles in osteosarcoma cells to help identify the key parameters relevant to choosing an effective gold nanoparticle-based radiosensitizer.

  2. 29 CFR 1915.57 - Uses of fissionable material in ship repairing and shipbuilding.

    Science.gov (United States)

    2010-07-01

    ... Commission's Standards for Protection Against Radiation (10 CFR part 20), relating to protection against... SHIPYARD EMPLOYMENT Welding, Cutting and Heating § 1915.57 Uses of fissionable material in ship repairing... activities involving the use of and exposure to sources of ionizing radiation not only on...

  3. Radiation dosimetry.

    OpenAIRE

    Cameron, J

    1991-01-01

    This article summarizes the basic facts about the measurement of ionizing radiation, usually referred to as radiation dosimetry. The article defines the common radiation quantities and units; gives typical levels of natural radiation and medical exposures; and describes the most important biological effects of radiation and the methods used to measure radiation. Finally, a proposal is made for a new radiation risk unit to make radiation risks more understandable to nonspecialists.

  4. Hematopoietic tissue repair under chronic low daily dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Seed, T.M.

    1994-12-01

    The capacity of the hematopoietic system to repair constantly accruing cellular damage under chronic, low daily dose gamma irradiation is essential for the maintenance of a functional hematopoietic system, and, in turn, long term survival. In certain individuals, however, such continuous cycles of damage and repair provide an essential inductive environment for selected types of hematopathologies, e.g., myeloid leukemia (ML). We have been studying temporal and causal relationships between hematopoietic capacity, associated repair functions, and propensities for hematologic disease in canines under variable levels of chronic radiation stress (0.3{minus}26.3 cGy d{sup {minus}1}). Results indicate that the maximum exposure rate tolerated by the hematopoietic system is highly individual-specific and is based largely on the degree to which repair capacity, and, in turn, hematopoietic restoration, is augmented under chronic exposure. In low-tolerance individuals (prone to aplastic anemia, subgroup (1), the failure to augment basic m-pair functions seemingly results in a progressive accumulation of genetic and cellular damage within vital progenitorial marrow compartments particularly marked within erythroid compartments. that results in loss of reproductive capacity and ultimately in collapse of the hematopoietic system. The high-tolerance individuals (radioaccomodated and either prone- or not prone to ML, subgroup 2 & 3 appear to minimize the accumulating damage effect of daily exposures by extending repair functions, which preserves reproductive integrity and fosters regenerative hematopoietic responses. As the strength of the regenerative response manifests the extent of repair augmentation, the relatively strong response of high- tolerance individuals progressing to patent ML suggests an insufficiency of repair quality rather than repair quantity.

  5. Identification of novel DNA repair proteins via primary sequence, secondary structure, and homology

    Directory of Open Access Journals (Sweden)

    Akutsu Tatsuya

    2009-01-01

    Full Text Available Abstract Background DNA repair is the general term for the collection of critical mechanisms which repair many forms of DNA damage such as methylation or ionizing radiation. DNA repair has mainly been studied in experimental and clinical situations, and relatively few information-based approaches to new extracting DNA repair knowledge exist. As a first step, automatic detection of DNA repair proteins in genomes via informatics techniques is desirable; however, there are many forms of DNA repair and it is not a straightforward process to identify and classify repair proteins with a single optimal method. We perform a study of the ability of homology and machine learning-based methods to identify and classify DNA repair proteins, as well as scan vertebrate genomes for the presence of novel repair proteins. Combinations of primary sequence polypeptide frequency, secondary structure, and homology information are used as feature information for input to a Support Vector Machine (SVM. Results We identify that SVM techniques are capable of identifying portions of DNA repair protein datasets without admitting false positives; at low levels of false positive tolerance, homology can also identify and classify proteins with good performance. Secondary structure information provides improved performance compared to using primary structure alone. Furthermore, we observe that machine learning methods incorporating homology information perform best when data is filtered by some clustering technique. Analysis by applying these methodologies to the scanning of multiple vertebrate genomes confirms a positive correlation between the size of a genome and the number of DNA repair protein transcripts it is likely to contain, and simultaneously suggests that all organisms have a non-zero minimum number of repair genes. In addition, the scan result clusters several organisms' repair abilities in an evolutionarily consistent fashion. Analysis also identifies several

  6. Molecular targets in cellular response to ionizing radiation and implications in space radiation protection

    Energy Technology Data Exchange (ETDEWEB)

    Belli, M.; Tabocchini, M.A. [Istituto Superiore di Sanita, Rome (Italy). Physics Lab.; Sapora, O. [Istituto Superiore di Sanita, Rome (Italy). Comparative Toxicology Lab.

    2002-12-01

    DNA repair systems and cell cycle checkpoints closely co-operate in the attempt of maintaining the genomic integrity of cells damaged by ionizing radiation. DNA double-strand breaks (DSB) are considered as the most biologically important radiation-induced damage. Their spatial distribution and association with other types of damage depend on radiation quality. It is believed these features affect damage reparability, thus explaining the higher efficiency for cellular effects of densely ionizing radiation with respect to {gamma}-rays. DSB repair systems identified in mammalian cells are homologous recombination (HR), single-strand annealing (SSA) and non-homologous end-joining (NHEJ). Some enzymes may participate in more than one of these repair systems. DNA damage also triggers biochemical signals activating checkpoints responsible for delay in cell cycle progression that allows more time for repair. Those at G1/S and S phases prevent replication of damaged DNA and those at G2/M phase prevent segregation of changed chromosomes. Individuals with lack or alterations of genes involved in DNA DSB repair and cell cycle checkpoints exhibit syndromes characterized by genome instability and predisposition to cancer. Information reviewed in this paper on the basic mechanisms of cellular response to ionizing radiation indicates their importance for a number of issues relevant to protection of astronauts from space radiation. (author)

  7. Staphylococcus aureus sepsis induces early renal mitochondrial DNA repair and mitochondrial biogenesis in mice.

    Directory of Open Access Journals (Sweden)

    Raquel R Bartz

    Full Text Available Acute kidney injury (AKI contributes to the high morbidity and mortality of multi-system organ failure in sepsis. However, recovery of renal function after sepsis-induced AKI suggests active repair of energy-producing pathways. Here, we tested the hypothesis in mice that Staphyloccocus aureus sepsis damages mitochondrial DNA (mtDNA in the kidney and activates mtDNA repair and mitochondrial biogenesis. Sepsis was induced in wild-type C57Bl/6J and Cox-8 Gfp-tagged mitochondrial-reporter mice via intraperitoneal fibrin clots embedded with S. aureus. Kidneys from surviving mice were harvested at time zero (control, 24, or 48 hours after infection and evaluated for renal inflammation, oxidative stress markers, mtDNA content, and mitochondrial biogenesis markers, and OGG1 and UDG mitochondrial DNA repair enzymes. We examined the kidneys of the mitochondrial reporter mice for changes in staining density and distribution. S. aureus sepsis induced sharp amplification of renal Tnf, Il-10, and Ngal mRNAs with decreased renal mtDNA content and increased tubular and glomerular cell death and accumulation of protein carbonyls and 8-OHdG. Subsequently, mtDNA repair and mitochondrial biogenesis was evidenced by elevated OGG1 levels and significant increases in NRF-1, NRF-2, and mtTFA expression. Overall, renal mitochondrial mass, tracked by citrate synthase mRNA and protein, increased in parallel with changes in mitochondrial GFP-fluorescence especially in proximal tubules in the renal cortex and medulla. Sub-lethal S. aureus sepsis thus induces widespread renal mitochondrial damage that triggers the induction of the renal mtDNA repair protein, OGG1, and mitochondrial biogenesis as a conspicuous resolution mechanism after systemic bacterial infection.

  8. Laparoscopic Repair of Morgagni Hernia

    Directory of Open Access Journals (Sweden)

    ilker murat arer

    2015-03-01

    Full Text Available Morgagni hernia is a congenital herniation of abdominal contents into the thoracic cavity through a retrosternal diaphragmatic defect and make up about 1 % - 5 % of all types of congenital diaphragmatic hernias. Surgical repair of Morgagni hernias is usually indicated when patients are symptomatic and have a high risk of strangulation or incarceration of the contained viscera. 71-year-old male patient admitted to emergency department with a 2-day history of abdominal pain, vomiting and obstipation. Laparoscopic repair for Morgagni hernia was performed. Laparoscopic repair for Morgagni hernia with mesh repair is secure, satisfactory and easily performed. [Cukurova Med J 2015; 40(Suppl 1: 71-74

  9. Combinatorial Reliability and Repair

    Science.gov (United States)

    1992-07-01

    Press, Oxford, 1987. [2] G. Gordon and L. Traldi, Generalized activities and the Tutte polynomial , Discrete Math. 85 (1990), 167-176. [3] A. B. Huseby, A...particular, Satyanarayana and Tindell introduced a notion of (K,j)-domination in their study of a K-terminal version of the chromatic polynomial [6], and it...G)) graphs. He also intends to look into the properties of the polynomial that gives the expected number of needed repairs of a K-terminal network

  10. Mammalian mismatch repair

    DEFF Research Database (Denmark)

    Pena Diaz, Javier; Jiricny, Josef

    2012-01-01

    A considerable surge of interest in the mismatch repair (MMR) system has been brought about by the discovery of a link between Lynch syndrome, an inherited predisposition to cancer of the colon and other organs, and malfunction of this key DNA metabolic pathway. This review focuses on recent...... advances in our understanding of the molecular mechanisms of canonical MMR, which improves replication fidelity by removing misincorporated nucleotides from the nascent DNA strand. We also discuss the involvement of MMR proteins in two other processes: trinucleotide repeat expansion and antibody maturation...

  11. Role for DNA polymerase beta in response to ionizing radiation.

    NARCIS (Netherlands)

    Vermeulen, C.; Verwijs-Janssen, M.; Cramers, P.; Begg, A.C.; Vens, C.

    2007-01-01

    Evidence for a role of DNA polymerase beta in determining radiosensitivity is conflicting. In vitro assays show an involvement of DNA polymerase beta in single strand break repair and base excision repair of oxidative damages, both products of ionizing radiation. Nevertheless the lack of DNA polymer

  12. BacMam immunization partially protects pigs against sublethal challenge with African swine fever virus.

    Science.gov (United States)

    Argilaguet, Jordi M; Pérez-Martín, Eva; López, Sergio; Goethe, Martin; Escribano, J M; Giesow, Katrin; Keil, Günther M; Rodríguez, Fernando

    2013-04-01

    Lack of vaccines and efficient control measures complicate the control and eradication of African swine fever (ASF). Limitations of conventional inactivated and attenuated virus-based vaccines against African swine fever virus (ASFV) highlight the need to use new technologies to develop efficient and safe vaccines against this virus. With this aim in mind, in this study we have constructed BacMam-sHAPQ, a baculovirus based vector for gene transfer into mammalian cells, expressing a fusion protein comprising three in tandem ASFV antigens: p54, p30 and the extracellular domain of the viral hemagglutinin (secretory hemagglutinin, sHA), under the control of the human cytomegalovirus immediate early promoter (CMVie). Confirming its correct in vitro expression, BacMam-sHAPQ induced specific T-cell responses directly after in vivo immunization. Conversely, no specific antibody responses were detectable prior to ASFV challenge. The protective potential of this recombinant vaccine candidate was tested by a homologous sublethal challenge with ASFV following immunization. Four out of six immunized pigs remained viremia-free after ASFV infection, while the other two pigs showed similar viremic titres to control animals. The protection afforded correlated with the presence of a large number of virus-specific IFNγ-secreting T-cells in blood at 17 days post-infection. In contrast, the specific antibody levels observed after ASFV challenge in sera from BacMam-sHAPQ immunized pigs were indistinguishable from those found in control pigs. These results highlight the importance of the cellular responses in protection against ASFV and point towards BacMam vectors as potential tools for future vaccine development.

  13. Lethal and Sublethal Effects of Insecticides Used on Citrus, on the Ectoparasitoid Tamarixia radiata.

    Science.gov (United States)

    Beloti, Vitor Hugo; Alves, Gustavo Rodrigues; Araújo, Diogo Feliciano Dias; Picoli, Mateus Manara; Moral, Rafael de Andrade; Demétrio, Clarice Garcia Borges; Yamamoto, Pedro Takao

    2015-01-01

    Huanglongbing (HLB) is a disease associated with the bacteria "Candidatus Liberibacter spp." and has been devastating citrus orchards around the world. Its management involves control of the insect vector, the Asian citrus psyllid Diaphorina citri Kuwayama. However, the indiscriminate use of chemicals has caused pest outbreaks and eliminated the natural enemies of the vector, such as the parasitoid Tamarixia radiata (Waterston), the main agent for biological control of D. citri. This study assessed the lethal and sublethal effects of insecticides recommended for integrated production of citrus on the parasitoid T. radiata. When adult parasitoids were exposed to residues of 25 insecticides, 20% of them, i.e., gamma-cyhalothrin, etofenprox, azadirachtin, tebufenozide and pyriproxyfen, were considered as harmless (Class 1), 12% as slightly harmful (Class 2), 12% as moderately harmful (Class 3) and 56% as harmful (Class 4), according to the classification proposed by the IOBC/WPRS. Afterward, 14 insecticides (5 harmless and 9 harmful) were sprayed on the parasitoid pupae. Of the 14 insecticides tested, only the organophosphates dimethoate and chlorpyrifos affected the parasitoid emergence. The effects of insecticides on the parasitism capacity of adults exposed to residues of azadirachtin, etofenprox, gamma-cyhalothrin, pyriproxyfen and tebufenozide (harmless) were also evaluated. Tebufenozide and gamma-cyhalothrin affected the parasitism of the F0 generation, but did not affect the emergence of the F1 and F2 generations. Therefore, for an effective IPM program, selective insecticides or harmful pesticides to adult parasitoids could be used in the field, provided that the adults do not occur naturally and the chemical applications do not coincide with parasitoid releases.

  14. Sublethal effects of two neurotoxican insecticides on Araneus pratensis (Araneae: Araneidae).

    Science.gov (United States)

    Benamú, M A; Schneider, M I; Pineda, S; Sanchez, N E; Gonzalez, A

    2007-01-01

    Spiders are important predators of several agricultural pests and they play an important role as indicators of ecosystem disturb. In Argentina, soybean crop has increased from the introduction of transgenic soybean resistant to glyphosate. This expansion produced an increase in the use of conventional and non-selective pesticides to control soybean pests. The objective of this work was to evaluate the side effects of subletal concentrations of two neurotoxican insecticides with a different mode of action: endosulfan (Glex, 35%, 25 mg/l a.i.) and spinosad (Tracer, 48%, 30 and 3 mg/l a.i) on Araneus pratensis. The insecticides were applied by ingestion of the treated prey (Musca domestica), and the effects on mortality, prey consumption, web building, mating, ootheca construction and fecundity were determined. Spinosad (30 mg/l a.i.) produced higher mortality than endosulfan (25 mg/l a.i.). Tremors and non-coordinated movements were observed in this treatment. The prey consumption was significantly reduced by the two insecticides (approximately 40% lower than control). The spider web building was significantly affected by the two insecticides, but spinosad had a greater effect. Though mating was not affected by both pesticides, abnormal oothecas and dehydrated eggs were observed. This work reports that sublethal concentrations representing approximately from 25 to 2.5% of the maximum field recommended concentrations (105 and 120 mg/l a.i., respectively) showed negative effects on A. pratensis. The consequences of these effects on role of A. pratensis as a natural mortality factor of soybean pests are discussed.

  15. Intramuscular Cobinamide Sulfite in a Rabbit Model of Sub-Lethal Cyanide Toxicity

    Science.gov (United States)

    Brenner, Matthew; Kim, Jae G.; Mahon, Sari B.; Lee, Jangwoen; Kreuter, Kelly A.; Blackledge, William; Mukai, David; Patterson, Steve; Mohammad, Othman; Sharma, Vijay S.; Boss, Gerry R.

    2009-01-01

    Objective To determine the ability of an intramuscular cobinamide sulfite injection to rapidly reverse the physiologic effects of cyanide toxicity. Background Exposure to cyanide in fires and industrial exposures and intentional cyanide poisoning by terrorists leading to mass casualties is an ongoing threat. Current treatments for cyanide poisoning must be administered intravenously, and no rapid treatment methods are available for mass casualty cyanide exposures. Cobinamide is a cobalamin (vitamin B12) analog with an extraordinarily high affinity for cyanide that is more water-soluble than cobalamin. We investigated the use of intramuscular cobinamide sulfite to reverse cyanide toxicity induced physiologic changes in a sublethal cyanide exposure animal model. Methods New Zealand white rabbits were given 10 mg sodium cyanide intravenously over 60 minutes. Quantitative diffuse optical spectroscopy and continuous wave near infrared spectroscopy monitoring of tissue oxy- and deoxyhemoglobin concentrations were performed concurrently with blood cyanide level measurements and cobinamide levels. Immediately after completion of the cyanide infusion, the rabbits were injected intramuscularly with cobinamide sulfite (n=6) or inactive vehicle (controls, n=5). Results Intramuscular administration led to rapid mobilization of cobinamide and was extremely effective at reversing the physiologic effects of cyanide on oxyhemoglobin and deoxyhemoglobin extraction. Recovery time to 63% of their baseline values in the central nervous system was in a mean of 1032 minutes in the control group and 9 minutes in the cobinamide group with a difference of 1023 minutes (95% confidence interval [CI] 116, 1874 minutes). In muscle tissue, recovery times were 76 and 24 minutes with a difference of 52 minutes (95% CI 7, 98min). Red blood cell cyanide levels returned towards normal significantly faster in cobinamide sulfite-treated animals than in control animals. Conclusions Intramuscular

  16. Sublethal effects of an organophosphorus insecticide (RPR-II) on biochemical parameters of tilapia, Oreochromis mossambicus.

    Science.gov (United States)

    Venkateswara Rao, J

    2006-08-01

    The effect of exposure to sublethal concentrations (0.017 mg L(-1), 1/10 of LC50) of the novel organophosphate (OP) insecticide, 2-butenoic acid-3-(diethoxyphosphinothioyl) methyl ester (RPR-II) on biochemical parameters in Oreochromis mossambicus was studied during exposure for 3, 7, 15, 30 and its recovery response after seven days. Acetylcholinesterase (AChE) activity of brain, gill and muscle was inhibited by 67%, 77% and 73% respectively on day-30. The plasma and kidney alanine aminotransferase (AlaAT), and aspartate aminotransferase (AspAT) activity increased, while decreases were observed in gill and liver. Increases in acid phosphatase (AcP), and alkaline phosphatase (AP) activities were observed in plasma, gill, and kidney, and reductions of 20% and 61% in liver AcP and AP, respectively. Depletion of glycogen was observed in all tissues, an indication of typical stress related response of the fish with pesticide. Lactate dehydrogenase (LDH) activity decreased in liver and muscle, indicating tissue damage but a significant increase in LDH activity in gill and brain was observed. Depletion of glutathione (GSH) was observed in all tissues, thereby enhancing lipid peroxidation resulting in cell damage. The induction in hepatic glutathione-S-transferase (GST) levels indicates protection against the toxicity of xenobiotic-induced lipid peroxidation. There was a significant recovery in the above biochemical parameters, in all tissues of fish after a recovery period of seven days. These results revealed that the OP insecticide RPR-II is highly toxic and affects the intermediary metabolism of O. mossambicus.

  17. Sublethal effects of insecticide seed treatments on two nearctic lady beetles (Coleoptera: Coccinellidae).

    Science.gov (United States)

    Moscardini, Valéria Fonseca; Gontijo, Pablo Costa; Michaud, J P; Carvalho, Geraldo Andrade

    2015-07-01

    Predatory insects often feed on plants or use plant products to supplement their diet, creating a potential route of exposure to systemic insecticides used as seed treatments. This study examined whether chlorantraniliprole or thiamethoxam might negatively impact Coleomegilla maculata and Hippodamia convergens when the beetles consumed the extrafloral nectar of sunflowers grown from treated seed. We reared both species on eggs of Ephestia kuehniella and then switched adult H. convergens to a diet of greenbugs, Schizaphis graminum, in order to induce oviposition in this species. Excised sunflower stems, either treated or control and refreshed every 48 h, were provided throughout larval development, or for the first week of adult life. Exposure of C. maculata larvae to chlorantraniliprole and thiamethoxam applied as seed treatments delayed adult emergence by prolonging the pupal period. When adults were exposed, thiamethoxam reduced the preoviposition period compared to chlorantraniliprole, whereas the latter treatment cause females to produce fewer clutches during the observation period. Larvae of C. maculata did not appear to obtain sufficient hydration from the sunflower stems and their subsequent fecundity and fertility were compromised in comparison to the adult exposure experiment where larvae received supplemental water during development. Exposure of H. convergens larvae to thiamethoxam skewed the sex ratio in favor of females; both materials reduced the egg viability of resulting adults and increased the period required for eclosion. Exposure of H. convergens adults to chlorantraniliprole reduced egg eclosion times compared to thiamethoxam and exposure to both insecticides reduced pupation times in progeny. The results indicate that both insecticides have negative, sublethal impacts on the biology of these predators when they feed on extrafloral nectar of sunflower plants grown from treated seed.

  18. The SOS response increases bacterial fitness, but not evolvability, under a sublethal dose of antibiotic.

    Science.gov (United States)

    Torres-Barceló, Clara; Kojadinovic, Mila; Moxon, Richard; MacLean, R Craig

    2015-10-07

    Exposure to antibiotics induces the expression of mutagenic bacterial stress-response pathways, but the evolutionary benefits of these responses remain unclear. One possibility is that stress-response pathways provide a short-term advantage by protecting bacteria against the toxic effects of antibiotics. Second, it is possible that stress-induced mutagenesis provides a long-term advantage by accelerating the evolution of resistance. Here, we directly measure the contribution of the Pseudomonas aeruginosa SOS pathway to bacterial fitness and evolvability in the presence of sublethal doses of ciprofloxacin. Using short-term competition experiments, we demonstrate that the SOS pathway increases competitive fitness in the presence of ciprofloxacin. Continued exposure to ciprofloxacin results in the rapid evolution of increased fitness and antibiotic resistance, but we find no evidence that SOS-induced mutagenesis accelerates the rate of adaptation to ciprofloxacin during a 200 generation selection experiment. Intriguingly, we find that the expression of the SOS pathway decreases during adaptation to ciprofloxacin, and this helps to explain why this pathway does not increase long-term evolvability. Furthermore, we argue that the SOS pathway fails to accelerate adaptation to ciprofloxacin because the modest increase in the mutation rate associated with SOS mutagenesis is offset by a decrease in the effective strength of selection for increased resistance at a population level. Our findings suggest that the primary evolutionary benefit of the SOS response is to increase bacterial competitive ability, and that stress-induced mutagenesis is an unwanted side effect, and not a selected attribute, of this pathway. © 2015 The Authors.

  19. Sublethal concentrations of silver nanoparticles affect the mechanical stability of biofilms.

    Science.gov (United States)

    Grün, Alexandra Y; Meier, Jutta; Metreveli, George; Schaumann, Gabriele E; Manz, Werner

    2016-12-01

    Bacterial biofilms are most likely confronted with silver nanoparticles (Ag NPs) as a pollutant stressor in aquatic systems. In this study, biofilms of Aquabacterium citratiphilum were exposed for 20 h to 30 and 70 nm citrate stabilized Ag NPs in low-dose concentrations ranging from 600 to 2400 μg l(-1), and the Ag NP-mediated effects on descriptive, structural, and functional biofilm characteristics, including viability, protein content, architecture, and mechanical stability, were investigated. Viability, based on the bacterial cell membrane integrity of A. citratiphilum, as determined by epifluorescence microscopy, remained unaffected after Ag NP exposure. Moreover, in contrast to information in the current literature, protein contents of cells and extracellular polymeric substances (EPS) and biofilm architecture, including dry mass, thickness, and density, were not significantly impacted by exposure to Ag NPs. However, the biofilms themselves served as effective sinks for Ag NPs, exhibiting enrichment factors from 5 to 8. Biofilms showed a greater capacity to accumulate 30 nm sized Ag NPs than 70 nm Ag NPs. Furthermore, Ag NPs significantly threatened the mechanical stability of biofilms, as determined by a newly developed assay. For 30 nm Ag NPs, the mechanical stability of biofilms decreased as the Ag NP concentrations applied to them increased. In contrast, 70 nm Ag NPs produced a similar decrease in mechanical stability for each applied concentration. Overall, this finding demonstrates that exposure to Ag NPs triggers remarkable changes in biofilm adhesion and/or cohesiveness. Because of biofilm-mediated ecological services, this response raises environmental concerns regarding Ag NP release into freshwater systems, even in sublethal concentrations.

  20. Metalloporphyrin Co(III)TMPyP ameliorates acute, sublethal cyanide toxicity in mice.

    Science.gov (United States)

    Benz, Oscar S; Yuan, Quan; Amoscato, Andrew A; Pearce, Linda L; Peterson, Jim

    2012-12-17

    The formation of Co(III)TMPyP(CN)(2) at pH 7.4 has been shown to be completely cooperative (α(H) = 2) with an association constant of 2.1 (±0.2) × 10(11). The kinetics were investigated by stopped-flow spectrophotometry and revealed a complicated net reaction exhibiting 4 phases at pH 7.4 under conditions where cyanide was in excess. The data suggest molecular HCN (rather than CN(-)) to be the attacking nucleophile around neutrality. The two slower phases do not seem to be present when cyanide is not in excess, and the other two phases have rates comparable to that observed for cobalamin, a known effective cyanide scavenger. Addition of bovine serum albumin (BSA) did not affect the cooperativity of cyanide binding to Co(III)TMPyP, only lowered the equilibrium constant slightly to 1.2 (±0.2) × 10(11) and had an insignificant effect on the observed rate. A sublethal mouse model was used to assess the effectiveness of Co(III)TMPyP as a potential cyanide antidote. The administration of Co(III)TMPyP to sodium cyanide intoxicated mice resulted in the time required for the surviving mice to right themselves from a supine position being significantly decreased (9 ± 2 min) compared to that of the controls (33 ± 2 min). All observations were consistent with the demonstrated antidotal activity of Co(III)TMPyP operating through a cyanide-binding (i.e., scavenging) mechanism.

  1. Physiological response of alligator gar juveniles (Atractosteus spatula) exposed to sub-lethal doses of pollutants.

    Science.gov (United States)

    González, Carlos Aguilera; Cruz, Julio; Alfaro, Roberto Mendoza

    2015-08-01

    Alligator gar populations have declined because of overfishing, habitat loss and pollution. Over time, the exposure to different pollutants have affected these fishes as a consequence of their high trophic level, bottom-dwelling habits and long life span. In order to evaluate the physiological effects of pollutants on alligator gar, juveniles (6, 12 and 24 months) were exposed to sub-lethal doses of diazinon, β-naphthoflavone (BNF) and 17 β-estradiol (E2) by intraperitoneal injection. After 2 days of exposure, liver samples were taken to determine the activities of acetylcholinesterase, butyrylcholinesterase and carboxylesterase; alkaline and acid phosphatases (ALP and ACP); ethoxyresorufin o-deethylase (EROD); glutathione s-transferase (GST); superoxide dismutase (SOD), and vitellogenin (VTG) concentration. Two additional bioassays consisting on the exposure of compounds through water or food were performed and after 4 and 28 days, respectively, biomarkers were determined. All esterases were inhibited in organisms exposed to diazinon as well as in 6-months gar exposed to E2 and BNF. In contrast, ALP activity increased in gar exposed to diazinon and E2, while ACP activity did not show any variations. No EROD activity was registered after exposure to the different pollutants, despite being one of the most sensitive and common detoxification biomarkers used for fishes. GST activity reduction was detected when gar were exposed to E2 and BNF, while SOD activity increased after exposure to diazinon and E2. Finally, VTG levels were higher in animals exposed to E2 compared to other treatments. Overall, these results suggest that alligator gar juveniles have a low biotransformation metabolism and show that they are especially sensitive to those pollutants affecting the nervous system.

  2. Methicillin-resistant Staphylococcus aureus phage plaque size enhancement using sublethal concentrations of antibiotics.

    Science.gov (United States)

    Kaur, Sandeep; Harjai, Kusum; Chhibber, Sanjay

    2012-12-01

    Phage therapy presents an alternative approach against the emerging methicillin-resistant Staphylococcus aureus (MRSA) threat. Some of the problems encountered during isolation of MRSA phages include the high prevalence of enteric phages in natural sources, nonspecific absorption of viable phage, and the formation of pinpoint or tiny plaques. The phage isolated in this study, MR-5, also formed tiny plaques against its host S. aureus ATCC 43300 (MRSA), making its detection and enumeration difficult. An improved method of increasing the plaque size of MRSA phage by incorporating sublethal concentrations of three different classes of antibiotics (inhibitors of protein synthesis) in the classical double-layer agar (DLA) method was investigated. The β-lactam and quinolone antibiotics commonly employed in earlier studies for increasing the plaque size did not show any significant effect on the plaque size of isolated MR-5 phage. Linezolid (oxazolidinone class), tetracycline, and ketolide antibiotics brought significant enhancements (3 times the original size) in the plaque size of MR-5 phage. Prior treatment with these antibiotics resulted in significant reductions in the time of adsorption and the latent period of MR-5 phage. To rule out whether the action of linezolid (which brought the maximum increase in plaque size) was specific for a single phage only, its effect on the plaque size of seven other S. aureus-specific phages was also assessed. Significant enhancements in the plaque size of these phages were observed. These results indicate that this modification can therefore safely be incorporated in the traditional DLA overlay method to search for new MRSA-virulent phages.

  3. Modulation of dopaminergic neurotransmission induced by sublethal doses of the organophosphate trichlorfon in cockroaches.

    Science.gov (United States)

    Stürmer, Graziele Daiane; de Freitas, Thiago Carrazoni; Heberle, Marines de Avila; de Assis, Dênis Reis; Vinadé, Lúcia; Pereira, Antônio Batista; Franco, Jeferson Luis; Dal Belo, Cháriston André

    2014-11-01

    Organophosphate (OP) insecticides have been used indiscriminately, based on their high dissipation rates and low residual levels in the environment. Despite the toxicity of OPs to beneficial insects is principally devoted to the acetylcholinesterase (AChE) inhibition, the physiological mechanisms underlying this activity remain poorly understood. Here we showed the pharmacological pathways that might be involved in severe alterations in the insect locomotion and grooming behaviors following sublethal administration of the OP Trichlorfon (Tn) (0.25, 0.5 and 1 µM) in Phoetalia pallida. Tn inhibited the acetylcholinesterase activity (46±6, 38±3 and 24±6 nmol NADPH/min/mg protein, n=3, patropine>oxotremorine>d-tubocurarine>tropicamide>methoctramine induced a decrease on Tn (0.5 µM)-induced grooming increase, respectively in order of potency. Metoclopramide (0.4 µM), a DA-D2 selective inhibitor decreased the Tn-induced grooming activity (158±12 s/30 min; n=29; p<0.05). Nevertheless, the effect of the selective DA-D1 receptor blocker SCH 23390 (1.85 µM) on the Tn (0.5 µM)-induced grooming increase was significative and more intense than that of metoclopramide (54±6 s/30 min; n=30; p<0.05). Taken together the results suggest that a cross-talking between cholinergic M1/M3 and dopaminergic D1 receptors at the insect nervous system may play a role in the OP-mediated behavioral alterations. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Sublethal Effects of Beauveria bassiana (Ascomycota: Hypocreales) on Life Table Parameters of Frankliniella occidentalis (Thysanoptera: Thripidae).

    Science.gov (United States)

    Zhang, Tao; Reitz, Stuart R; Wang, Haihong; Lei, Zhongren

    2015-06-01

    We assessed effects of parental exposure to Beauveria bassiana on life history traits of subsequent generations of western flower thrips, Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae). Progeny from individuals that survived fungal exposure as second instars had significantly shorter egg stages, but longer prepupal development times than corresponding untreated controls. However, survivorship to adulthood of these progeny groups did not differ. Although fecundities of the parental types did not differ, the sex ratio of progeny from fungal-treated parents was male-biased, whereas sex ratio of progeny from untreated control parents was even. We calculated life table parameters for the progeny and found that all parameters, except for generation time, were significantly less for the progeny of fungal-treated parents than for progeny of untreated parents. The intrinsic rate of increase, finite rate of increase, net reproductive rate, mean generation time, and gross reproductive rate were 0.199 d(-1), 1.229 d(-1), 21.84, 15.48 d, and 27.273, respectively, for progeny of treated thrips, and 0.266 d(-1), 1.316 d(-1), 52.540, 14.92 d, and 70.64, respectively, for progeny of control thrips. Consequently, population projections demonstrated that offspring of parents exposed to B. bassiana would increase their population more slowly than those from untreated parents. These results demonstrate that B. bassiana has sublethal effects that reduce the reproductive success of F. occidentalis and these effects should be taken into account when evaluating its use in management programs for F. occidentalis.

  5. DNA replication, repair, and repair tests. [Rat; human leukocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lambert, B.

    1980-09-01

    The rate of inhibition and recovery of DNA synthesis can be used in a rapid assay system to detect genotoxic potentials of chemicals. Also, the observation that an agent stimulates DNA repair in a test system indicates its ability to cause damage in DNA. Different experimental approaches to the study of repair synthesis are discussed.

  6. Biologics for tendon repair.

    Science.gov (United States)

    Docheva, Denitsa; Müller, Sebastian A; Majewski, Martin; Evans, Christopher H

    2015-04-01

    Tendon injuries are common and present a clinical challenge to orthopedic surgery mainly because these injuries often respond poorly to treatment and require prolonged rehabilitation. Therapeutic options used to repair ruptured tendons have consisted of suture, autografts, allografts, and synthetic prostheses. To date, none of these alternatives has provided a successful long-term solution, and often the restored tendons do not recover their complete strength and functionality. Unfortunately, our understanding of tendon biology lags far behind that of other musculoskeletal tissues, thus impeding the development of new treatment options for tendon conditions. Hence, in this review, after introducing the clinical significance of tendon diseases and the present understanding of tendon biology, we describe and critically assess the current strategies for enhancing tendon repair by biological means. These consist mainly of applying growth factors, stem cells, natural biomaterials and genes, alone or in combination, to the site of tendon damage. A deeper understanding of how tendon tissue and cells operate, combined with practical applications of modern molecular and cellular tools could provide the long awaited breakthrough in designing effective tendon-specific therapeutics and overall improvement of tendon disease management.

  7. Kvitebjoern gas pipeline repair - baptism of remote pipeline repair system

    Energy Technology Data Exchange (ETDEWEB)

    Gjertveit, Erling

    2010-07-01

    On the 1st of November 2007, severe anchor damage was discovered on the 30 inch Kvitebjoern gas export pipeline. The damage constituted a localised dent and a 17deg buckle, but no leakage. Statoil has invested in building an effective repair contingency structure for the large pipeline network on the Norwegian Continental shelf, with particular focus on the large gas export pipelines. The repair method for the Kvitebjoern pipeline was remotely operated using two Morgrip couplings and a spool. The installation used the purpose built Pipeline Repair System stored at Killingoey and couplings produced and tested back in 2005. This presentation will cover the initial damage investigations, the temporary operational phase, the repair preparations, the actual repair and lessons learned. (Author)

  8. Genetics of x-ray induced double strand break repair in saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Budd, M.E.

    1982-07-01

    The possible fates of x-ray-induced double-strand breaks in Saccharomyces cerevisiae were examined. One possible pathway which breaks can follow, the repair pathway, was studied by assaying strains with mutations in the RAD51, RAD54, and RAD57 loci for double-strand break repair. In order of increasing radiation sensitivity one finds: rad57-1(23/sup 0/)> rad51-1(30/sup 0/)> rad54-3(36/sup 0/). At 36/sup 0/, rad54-3 cells cannot repair double-strand breaks, while 23/sup 0/, they can. Strains with the rad57-1 mutation can rejoin broken chromosomes at both temperatures. However, the low survival at 36/sup 0/ shows that the assay is not distinguishing large DNA fragments which allow cell survival from those which cause cell death. A rad51-1 strain could also rejoin broken chromosomes, and was thus capable of incomplete repair. The data can be explained with the hypothesis that rad54-3 cells are blocked in an early step of repair, while rad51-1 and rad57-1 strains are blocked in a later step of repair. The fate of double-strand breaks when they are left unrepaired was investigated with the rad54-3 mutation. If breaks are prevented from entering the RAD54 repair pathway they become uncommitted lesions. These lesions are repaired slower than the original breaks. One possible fate for an uncommitted lesion is conversion into a fixed lesion, which is likely to be an unrepairable or misrepaired double-strand break. The presence of protein synthesis after irradiation increases the probability that a break will enter the repair pathway. Evidence shows that increased probability of repair results from enhanced synthesis of repair proteins shortly after radiation. (ERB)

  9. Handbook of adhesive bonded structural repair

    CERN Document Server

    Wegman, Raymond F

    1992-01-01

    Provides repair methods for adhesive bonded and composite structures; identifies suitable materials and equipment for repairs; describes damage evaluation criteria and techniques, and methods of inspection before and after repair.

  10. Relations between conspecific density and effects of ultraviolet-b radiation on tadpole size in the striped marsh frog.

    Science.gov (United States)

    Mitchell, Toby; Alton, Lesley A; White, Craig R; Franklin, Craig E

    2012-12-01

    Global increases in ultraviolet-B radiation (UVBR) associated with stratospheric ozone depletion are potentially contributing to the decline of numerous amphibian species around the world. Exposure to UVBR alone reduces survival and induces a range of sublethal effects in embryonic and larval amphibians. When additional environmental stressors are present, UVBR can have compounding negative effects. Thus, examination of the effects of UVBR in the absence of other stressors may substantially underestimate its potential to affect amphibians in natural habitats. We examined the independent and interactive effects of increased UVBR and high conspecific density would have embryonic and larval striped marsh frogs (Limnodynastes peronii). We exposed individuals to a factorial combination of low and high UVBR levels and low, medium, and high densities of striped marsh frog tadpoles. The response variables were time to hatching, hatching success, posthatch survival, burst-swimming performance of tadpoles (maximum instantaneous swim speed following an escape response), and size and morphology of tadpoles. Consistent with results of previous studies, we found that exposure to UVBR alone increased the time to hatching of embryos and reduced the burst-swimming performance and size of tadpoles. Similarly, increasing conspecific density increased the time to hatching of embryos and reduced the size of tadpoles, but had no effect on burst-swimming performance. The negative effect of UVBR on tadpole size was not apparent at high densities of tadpoles. This result suggests that tadpoles living at higher densities may invest relatively less energy in growth and thus have more energy to repair UVBR-induced damage. Lower densities of conspecifics increased the negative effects of UVBR on developing amphibians. Thus, low-density populations, which may include declining populations, may be particularly susceptible to the detrimental effects of increased UVBR and thus may be driven toward

  11. Clamp wins pipe repair prize

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2001-04-01

    This paper describes the permanent pipeline repair system, developed by Tekmar, which is powered by seawater hydraulics and is easily installed and tested by any workclass remotely operated vehicle (rov). Details are given of the two main components of the system, namely, the diverless high pressure split repair clamp and the rov-operated tool to install it.

  12. The journey of DNA repair

    OpenAIRE

    Saini, Natalie

    2015-01-01

    21 years ago, the DNA Repair Enzyme was declared “Molecule of the Year”. Today, we are celebrating another “year of repair”, with the 2015 Nobel Prize in Chemistry being awarded to Aziz Sancar, Tomas Lindahl and Paul Modrich for their collective work on the different DNA repair pathways.

  13. Nucleotide excision repair in yeast

    NARCIS (Netherlands)

    Eijk, Patrick van

    2012-01-01

    Nucleotide Excision Repair (NER) is a conserved DNA repair pathway capable of removing a broad spectrum of DNA damage. In human cells a defect in NER leads to the disorder Xeroderma pigmentosum (XP). The yeast Saccharomyces cerevisiae is an excellent model organism to study the mechanism of NER. The

  14. Fipronil promotes motor and behavioral changes in honey bees (Apis mellifera) and affects the development of colonies exposed to sublethal doses.

    Science.gov (United States)

    Zaluski, Rodrigo; Kadri, Samir Moura; Alonso, Diego Peres; Martins Ribolla, Paulo Eduardo; de Oliveira Orsi, Ricardo

    2015-05-01

    Bees play a crucial role in pollination and generate honey and other hive products; therefore, their worldwide decline is cause for concern. New broad-spectrum systemic insecticides such as fipronil can harm bees and their use has been discussed as a potential threat to bees' survival. In the present study, the authors evaluate the in vitro toxicity of fipronil and note behavioral and motor activity changes in Africanized adult Apis mellifera that ingest or come into contact with lethal or sublethal doses of fipronil. The effects of sublethal doses on brood viability, population growth, behavior, and the expression of the defensin 1 gene in adult bees were studied in colonies fed with contaminated sugar syrup (8 µg fipronil L(-1) ). Fipronil is highly toxic to bees triggering agitation, seizures, tremors, and paralysis. Bees that are exposed to a lethal or sublethal doses showed reduced motor activity. The number of eggs that hatched, the area occupied by worker eggs, and the number of larvae and pupae that developed were reduced, adult bees showed lethargy, and colonies were abandoned when they were exposed to sublethal doses of fipronil. No change was seen in the bees' expression of defensin 1. The authors conclude that fipronil is highly toxic to honey bees and even sublethal doses may negatively affect the development and maintenance of colonies.

  15. DNA Repair Defects and Chromosomal Aberrations

    Science.gov (United States)

    Hada, Megumi; George, K. A.; Huff, J. L.; Pluth, J. M.; Cucinotta, F. A.

    2009-01-01

    Yields of chromosome aberrations were assessed in cells deficient in DNA doublestrand break (DSB) repair, after exposure to acute or to low-dose-rate (0.018 Gy/hr) gamma rays or acute high LET iron nuclei. We studied several cell lines including fibroblasts deficient in ATM (ataxia telangiectasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. Chromosomes were analyzed using the fluorescence in situ hybridization (FISH) chromosome painting method in cells at the first division post irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma irradiation induced greater yields of both simple and complex exchanges in the DSB repair-defective cells than in the normal cells. The quadratic dose-response terms for both simple and complex chromosome exchanges were significantly higher for the ATM- and NBS-deficient lines than for normal fibroblasts. However, in the NBS cells the linear dose-response term was significantly higher only for simple exchanges. The large increases in the quadratic dose-response terms in these repair-defective cell lines points the importance of the functions of ATM and NBS in chromatin modifications to facilitate correct DSB repair and minimize the formation of aberrations. The differences found between ATM- and NBS-deficient cells at low doses suggest that important questions should with regard to applying observations of radiation sensitivity at high dose to low-dose exposures. For aberrations induced by iron nuclei, regression models preferred purely linear dose responses for simple exchanges and quadratic dose responses for complex exchanges. Relative biological effectiveness (RBE) factors of all of

  16. DNA Repair Defects and Chromosomal Aberrations

    Science.gov (United States)

    Hada, Megumi; George, K. A.; Huff, J. L.; Pluth, J. M.; Cucinotta, F. A.

    2009-01-01

    Yields of chromosome aberrations were assessed in cells deficient in DNA doublestrand break (DSB) repair, after exposure to acute or to low-dose-rate (0.018 Gy/hr) gamma rays or acute high LET iron nuclei. We studied several cell lines including fibroblasts deficient in ATM (ataxia telangiectasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. Chromosomes were analyzed using the fluorescence in situ hybridization (FISH) chromosome painting method in cells at the first division post irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma irradiation induced greater yields of both simple and complex exchanges in the DSB repair-defective cells than in the normal cells. The quadratic dose-response terms for both simple and complex chromosome exchanges were significantly higher for the ATM- and NBS-deficient lines than for normal fibroblasts. However, in the NBS cells the linear dose-response term was significantly higher only for simple exchanges. The large increases in the quadratic dose-response terms in these repair-defective cell lines points the importance of the functions of ATM and NBS in chromatin modifications to facilitate correct DSB repair and minimize the formation of aberrations. The differences found between ATM- and NBS-deficient cells at low doses suggest that important questions should with regard to applying observations of radiation sensitivity at high dose to low-dose exposures. For aberrations induced by iron nuclei, regression models preferred purely linear dose responses for simple exchanges and quadratic dose responses for complex exchanges. Relative biological effectiveness (RBE) factors of all of

  17. Effects of sublethal exposure to metofluthrin on the fitness of Aedes aegypti in a domestic setting in Cairns, Queensland.

    Science.gov (United States)

    Buhagiar, Tamara S; Devine, Gregor J; Ritchie, Scott A

    2017-05-31

    Metofluthrin is highly effective at reducing biting activity in Aedes aegypti. Its efficacy lies in the rapid onset of confusion, knockdown, and subsequent kill of a mosquito. In the field, there are a variety of scenarios that might result in sublethal exposure to metofluthrin, including mosquitoes that are active at the margins of the chemical's lethal range, brief exposure as mosquitoes fly in and out of treated spaces or decreasing efficacy of the emanators with time. Sublethal effects are key elements of insecticide exposure and selection. The metofluthrin dose for each treatment group of male and female Ae. aegypti was controlled using exposure time intervals to a 10% active ingredient (AI) metofluthrin emanator. Room size and distance from the emanator for all groups was maintained at 3 m. In bioassay cages, male Ae. aegypti were exposed at 0, 5, 10, 20, 30 and 40-min intervals. Females were exposed in bioassay cages at 0, 10, 20, 30, 40 and 60-min intervals. Mortality rates and fecundity were observed between the exposure time groups for both sexes. Female Ae. aegypti exposed for 60 min had a significantly higher mortality rate (50%), after a 24-h recovery period, than other exposure times, 10, 20, 30 and 40 min (P metofluthrin exposure were as likely to produce viable eggs with an unexposed female as males that had not been exposed (P > 0.05). Regardless of sex, if a mosquito survived exposure, it would be as biologically successful as its unexposed counterpart. Portability of the metofluthrin emanator and delayed knockdown effects create opportunities for sublethal exposure and potential pyrethroid resistance development in Ae. aegypti, and should be taken into consideration in recommendations for field application of this product, including minimum exposure periods and a prescribed number of emanators per room based on volume.

  18. Sublethal exposure to diatomaceous earth increases net fecundity of flour beetles (Tribolium confusum) by inhibiting egg cannibalism.

    Science.gov (United States)

    Shostak, Allen W

    2014-01-01

    Population regulation results from an interplay of numerous intrinsic and external factors, and for many insects cannibalism is such a factor. This study confirms a previously-reported observation that sublethal exposure to the fossilized remains of diatoms (i.e. diatomaceous earth) increases net fecundity (eggs produced minus eggs destroyed/day) of flour beetles, Tribolium confusum. The aim was to experimentally test two non-mutually-exclusive ecological mechanisms potentially responsible for the increased net fecundity: higher egg production and lower egg cannibalism. Adult T. confusum were maintained at low or high density in medium containing sublethal (0-4%) diatomaceous earth. Net fecundity increased up to 2.1× control values during diatomaceous earth exposure, and returned to control levels following removal from diatomaceous earth. Cannibalism assays on adults showed that diatomaceous earth reduced the number of eggs produced to 0.7× control values at low density and to 0.8× controls at high density, and also reduced egg cannibalism rates of adults to as little as 0.4× control values, but at high density only. Diatomaceous earth also reduced cannibalism by larvae on eggs to 0.3× control values. So, while the presence of diatomaceous earth reduced egg production, net fecundity increased as a result of strong suppression of the normal egg cannibalism by adults and larvae that occurs at high beetle density. Undisturbed cultures containing sublethal diatomaceous earth concentrations reached higher population densities than diatomaceous earth-free controls. Cohort studies on survival from egg to adult indicated that this population increase was due largely to decreased egg cannibalism by adult females. This is the first report of inhibition of egg cannibalism by diatomaceous earth on larval or adult insects. The ability of diatomaceous earth to alter cannibalism behavior without causing mortality makes it an ideal investigative tool for cannibalism studies.

  19. Sublethal exposure to diatomaceous earth increases net fecundity of flour beetles (Tribolium confusum by inhibiting egg cannibalism.

    Directory of Open Access Journals (Sweden)

    Allen W Shostak

    Full Text Available Population regulation results from an interplay of numerous intrinsic and external factors, and for many insects cannibalism is such a factor. This study confirms a previously-reported observation that sublethal exposure to the fossilized remains of diatoms (i.e. diatomaceous earth increases net fecundity (eggs produced minus eggs destroyed/day of flour beetles, Tribolium confusum. The aim was to experimentally test two non-mutually-exclusive ecological mechanisms potentially responsible for the increased net fecundity: higher egg production and lower egg cannibalism. Adult T. confusum were maintained