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Sample records for damage site mutagenic

  1. Miscoding and mutagenic properties of 8-oxoguanine and abasic sites: Ubiquitous lesions in damaged DNA

    International Nuclear Information System (INIS)

    Grollman, A.P.; Takeshita, Masaru

    1995-01-01

    More than twenty oxidatively-damaged bases, including 8-oxoguanine, have been found to occur in genomic DNA. Some of these lesions block DNA replication and are potentially lethal; others generate mutations which can initiate carcinogenesis and promote cellular aging. In this report, the authors focus attention on the mutagenicity and repair of 8-oxoguanine. Kasai and Nishimura's discovery that hydroxyl radicals react with guanine residues in DNA to form 8-oxoguanine and the development of sensitive methods for the detection and quantitation of this modified base led to the observation that approximately 1 in 10 5 guanine residues in mammalian DNA are oxidized at the C-8 position. DNA containing 8-oxoguanine and synthetic analogs of the abasic site have been used to investigate the miscoding and mutagenic potential of these ubiquitous lesions. Studies in the laboratory were facilitated by the development of solid state synthetic methods by which these lesions could be introduced at defined positions in DNA. In this paper, the authors review studies in which 8-oxoguanine and abasic sites have been used in model systems to explore various early events in the replication of selectively damaged DNA

  2. Bacterial mutagenicity and mammalian cell DNA damage by several substituted anilines.

    Science.gov (United States)

    Zimmer, D; Mazurek, J; Petzold, G; Bhuyan, B K

    1980-04-01

    Several substituted alkyl- and haloanilines were tested for their ability to mutate Salmonella typhimurium and to damage the DNA of mammalian (V79) cells. These results were correlated with their reported carcinogenicity. Of 9 suspected carcinogens, 4 were bacterial mutagens and 4 (out of 7 tested) damaged DNA of V79 cells. The following compounds were weakly mutagenic (less than 150 revertants/mumole): 4-fluoroaniline, 2,3-, 2,4-, 2,5- and 3,4-dimethylaniline, and 2-methyl-4-fluoroaniline. The following compounds were strong mutagens: 2,4,5-trimethylaniline, 2-methyl-4-chloro-, and 2-methyl-4-bromo-, 4-methyl-2-chloro-, 4-methyl-2-bromo- and 2-ethyl-4-chloroaniline. The compounds which damaged DNA in V79 cells were: 2 methyl-4-chloroaniline, 2-methyl-4-bromoaniline, 2,4,5- and 2,4,6-trimethylaniline.

  3. Oxygen effect on mutagenic ionizing radiation damage in Bacillus subtilis spores of DNA polymerase I-proficient and -deficient strains

    International Nuclear Information System (INIS)

    Tanooka, H.

    1980-01-01

    The nature of mutagenic ionizing radiation damage modified by the presence of oxygen or water was examined by comparing mutagenic with lethal expression of the damage in Bacillus subtilis spores irradiated with 6-MeV electrons. No specific difference was recognized between oxygen-dependent and -independent damages or between polA + -dependent and -independent damages with this system. The induced mutation frequency for His + mutation per lethal hit was 4.7 x 10 -5 for all tested cases

  4. Mutagenic and DNA damaging activity in muscle of trout exposed in vivo to nitrite

    Energy Technology Data Exchange (ETDEWEB)

    De Flora, S; Arillo, A

    1983-09-01

    Muscle ether extracts of rainbow trout (Salmo gairdneri) exposed to lake water enriched with nitrite (450 micrograms/l) reverted plasmid-containing his- strains of Salmonella typhimurium, mainly eliciting frameshift mutations, and induced a DNA damage in Escherichia coli reparable through the recA/lexA-dependent SOS functions. The number of revertants was related to their content in nitroso-derivatives and to the physiological condition of the fish. Mutagenicity was efficiently decreased, through NADPH-requiring pathways, by liver S-9 fractions from rats or rainbow trout, while it was not affected by preliminary heating nor by pre-incubation with human gastric juice.

  5. Induction of Abasic Sites by the Drinking-Water Mutagen MX in Salmonella TA100

    Science.gov (United States)

    Mutagen X (MX) is a chlorinated furanone that accounts for more of the mutagenic activity of drinking water than any other disinfection by-product. It is one of the most potent base-substitution mutagens in the Salmonella (Ames) mutagenicity assay, producing primarily GC to TA mu...

  6. Circular dichroism study of the interaction between mutagens and bilirubin bound to different binding sites of serum albumins

    Science.gov (United States)

    Orlov, Sergey; Goncharova, Iryna; Urbanová, Marie

    Although recent investigations have shown that bilirubin not only has a negative role in the organism but also exhibits significant antimutagenic properties, the mechanisms of interactions between bilirubin and mutagens are not clear. In this study, interaction between bilirubin bound to different binding sites of mammalian serum albumins with structural analogues of the mutagens 2-aminofluorene, 2,7-diaminofluorene and mutagen 2,4,7-trinitrofluorenone were investigated by circular dichroism and absorption spectroscopy. Homological human and bovine serum albumins were used as chiral matrices, which preferentially bind different conformers of bilirubin in the primary binding sites and make it observable by circular dichroism. These molecular systems approximated a real system for the study of mutagens in blood serum. Differences between the interaction of bilirubin bound to primary and to secondary binding sites of serum albumins with mutagens were shown. For bilirubin bound to secondary binding sites with low affinity, partial displacement and the formation of self-associates were observed in all studied mutagens. The associates of bilirubin bound to primary binding sites of serum albumins are formed with 2-aminofluorene and 2,4,7-trinitrofluorenone. It was proposed that 2,7-diaminofluorene does not interact with bilirubin bound to primary sites of human and bovine serum albumins due to the spatial hindrance of the albumins binding domains. The spatial arrangement of the bilirubin bound to serum albumin along with the studied mutagens was modelled using ligand docking, which revealed a possibility of an arrangement of the both bilirubin and 2-aminofluorene and 2,4,7-trinitrofluorenone in the primary binding site of human serum albumin.

  7. Quantitative changes in endogenous DNA damage correlate with conazole mutagenicity and tumorigenicity.

    Science.gov (United States)

    The mouse liver tumorigenic conazolefungicides triadimefon and propiconazole have previously been shown to be in vivo mouse liver mutagens in the Big Blue" transgenic mutation assay when administered in feed at tumorigenic doses, whereas the nontumorigenic conazole myclobutanil w...

  8. Comparison of BTX Profiles and Their Mutagenicity Assessment at Two Sites of Agra, India

    Directory of Open Access Journals (Sweden)

    Vyoma Singla

    2012-01-01

    Full Text Available In the present study, the concentrations of three volatile organic compounds (VOCs, namely, acronym for benzene, toluene, and xylenes (BTX were assessed because of their role in the tropospheric chemistry. Two representative sites, a roadside and a petrol pump, were chosen for sample collection. VOCs were collected using SKC-activated charcoal tubes and SKC personal sampler and characterized by gas chromatograph using flame ionization detector. Among BTX, benzene had the highest concentration. At the roadside, mean concentration of benzene, toluene, o-,m-xylene, and p-xylene were 14.7 ± 2.4 μgm−3, 8.1 ± 1.2 μgm−3, 2.1 ± 0.8 μgm−3, and 5.1 ± 1.2 μgm−3, respectively. At the petrol pump, the mean concentrations of benzene, toluene, o-,m-xylene and p-xylene were 19.5 ± 3.7 μgm−3, 12.9 ± 1.1 μgm−3, 3.6 ± 0.5 μgm−3 and 11.1 ± 1.5 μgm−3, respectively, and were numerically higher by a fraction of 2. Monthly variation of BTX showed maximum concentration in winter. Inter-species ratios and inter-species correlation indicated traffic as the major source of BTX. Extracts of samples were positive in both Salmonella typhimurium tester strains TA98 and TA100 without metabolic activation suggesting the presence of direct mutagens in ambient air that can cause both frame-shift and base-pair mutation. The mutagenic response was greater for TA100 than TA98 suggesting greater activity for base-pair mutagenicity than frame-shift mutagenicity and was found to be statistically significant.

  9. Multiple Site Damage in Flat Panel Testing

    National Research Council Canada - National Science Library

    Shrage, Daniel

    2000-01-01

    This report aimed to experimentally verify analytical models that predict the residual strength of representative aircraft structures, such as wide panels, that are subjected to Multiple Site Damage (MSD...

  10. Studying the synergistic damage effects induced by 1.8 GHz radiofrequency field radiation (RFR) with four chemical mutagens on human lymphocyte DNA using comet assay in vitro

    International Nuclear Information System (INIS)

    Wang Baohong; He Jiliang; Jin Lifen; Lu Deqiang; Zheng Wei; Lou Jianlin; Deng Hongping

    2005-01-01

    The aim of this investigation was to study the synergistic DNA damage effects in human lymphocytes induced by 1.8 GHz radiofrequency field radiation (RFR, SAR of 3 W/kg) with four chemical mutagens, i.e. mitomycin C (MMC, DNA crosslinker), bleomycin (BLM, radiomimetic agent), methyl methanesulfonate (MMS, alkylating agent), and 4-nitroquinoline-1-oxide (4NQO, UV-mimetic agent). The DNA damage of lymphocytes exposed to RFR and/or with chemical mutagens was detected at two incubation time (0 or 21 h) after treatment with comet assay in vitro. Three combinative exposure ways were used. Cells were exposed to RFR and chemical mutagens for 2 and 3 h, respectively. Tail length (TL) and tail moment (TM) were utilized as DNA damage indexes. The results showed no difference of DNA damage indexes between RFR group and control group at 0 and 21 h incubation after exposure (P > 0.05). There were significant difference of DNA damage indexes between MMC group and RFR + MMC co-exposure group at 0 and 21 h incubation after treatment (P 0.05). The experimental results indicated 1.8 GHz RFR (SAR, 3 W/kg) for 2 h did not induce the human lymphocyte DNA damage effects in vitro, but could enhance the human lymphocyte DNA damage effects induced by MMC and 4NQO. The synergistic DNA damage effects of 1.8 GHz RFR with BLM or MMS were not obvious

  11. Evaluation of DNA damage and mutagenicity induced by lead in tobacco plants.

    Science.gov (United States)

    Gichner, Tomás; Znidar, Irena; Száková, Jirina

    2008-04-30

    Tobacco (Nicotiana tabacum L. var. xanthi) seedlings were treated with aqueous solutions of lead nitrate (Pb2+) at concentrations ranging from 0.4 mM to 2.4 mM for 24 h and from 25 microM to 200 microM for 7 days. The DNA damage measured by the comet assay was high in the root nuclei, but in the leaf nuclei a slight but significant increase in DNA damage could be demonstrated only after a 7-day treatment with 200 microM Pb2+. In tobacco plants growing for 6 weeks in soil polluted with Pb2+ severe toxic effects, expressed by the decrease in leaf area, and a slight but significant increase in DNA damage were observed. The tobacco plants with increased levels of DNA damage were severely injured and showed stunted growth, distorted leaves and brown root tips. The frequency of somatic mutations in tobacco plants growing in the Pb2+-polluted soil did not significantly increase. Analytical studies by inductively coupled plasma optical emission spectrometry demonstrate that after a 24-h treatment of tobacco with 2.4 mM Pb2+, the accumulation of the heavy metal is 40-fold higher in the roots than in the above-ground biomass. Low Pb2+ accumulation in the above-ground parts may explain the lower levels or the absence of Pb2+-induced DNA damage in leaves.

  12. Assessment of mutagenic damage by monofunctional alkylating agents and gamma radiation in haploid and diploid frogs, Xenopus laevis

    International Nuclear Information System (INIS)

    Hart, D.R.; Armstrong, J.B.

    1984-01-01

    Adult male South African clawed frogs, Xenopus laevis, were mutagenized by 3-day immersion in aqueous solutions of ethyl methanesulfonate (EMS), diethyl nitrosamine (DEN), or ethyl nitrosourea (ENU), or by acute exposure to gamma radiation. They were then spawned repeatedly at 2-week intervals with untreated females, and embryonic survival of the progeny was used to assess genetic damage. Recessive lethal effects were assessed from reduced survival of androgenetic haploid progeny. Neither recessive nor dominant lethal effects were obtained after exposure to 100 mg/liter EMS or 2 g/liter DEN. At 250 mg/liter EMS, peak dominant lethality occurred 3-5 weeks after treatment. Most embryos hatched, but many were abnormal and died shortly after hatching. Haploid survival was significantly reduced over a broader period, from 1 to 13 weeks after mutagenesis. Treatment with 75 mg/liter ENU produced effects similar to the 250-mg/liter EMS mutagenesis. At 400 mg/liter EMS, the frequency and severity of the effects on both diploid and haploid embryos were increased over the lower dose. Gamma irradiation at 1500 R produced effects similar to the 400-mg/liter mutagenesis, except that peak dominant lethality extended from 1 to 7 weeks

  13. Mutagenicity and oxidative damage induced by an organic extract of the particulate emissions from a simulation of the deepwater horizon surface oil burns.

    Science.gov (United States)

    DeMarini, David M; Warren, Sarah H; Lavrich, Katelyn; Flen, Alexis; Aurell, Johanna; Mitchell, William; Greenwell, Dale; Preston, William; Schmid, Judith E; Linak, William P; Hays, Michael D; Samet, James M; Gullett, Brian K

    2017-04-01

    Emissions from oil fires associated with the "Deepwater Horizon" explosion and oil discharge that began on April 20, 2010 in the Gulf of Mexico were analyzed chemically to only a limited extent at the time but were shown to induce oxidative damage in vitro and in mice. To extend this work, we burned oil floating on sea water and performed extensive chemical analyses of the emissions (Gullett et al., Marine Pollut Bull, in press, ). Here, we examine the ability of a dichloromethane extract of the particulate material with an aerodynamic size ≤ 2.5 µm (PM 2.5 ) from those emissions to induce oxidative damage in human lung cells in vitro and mutagenicity in 6 strains of Salmonella. The extract had a percentage of extractable organic material (EOM) of 7.0% and increased expression of the heme oxygenase (HMOX1) gene in BEAS-2B cells after exposure for 4 hr at 20 µg of EOM/ml. However, the extract did not alter mitochondrial respiration rate as measured by extracellular flux analysis. The extract was most mutagenic in TA100 +S9, indicative of a role for polycyclic aromatic hydrocarbons (PAHs), reflective of the high concentrations of PAHs in the emissions (1 g/kg of oil consumed). The extract had a mutagenicity emission factor of 1.8 ± 0.1 × 10 5 revertants/megajoule thermal in TA98 +S9, which was greater than that of diesel exhaust and within an order of magnitude of open burning of wood and plastic. Thus, organics from PM 2.5 of burning oil can induce oxidative responses in human airway epithelial cells and are highly mutagenic. Environ. Mol. Mutagen. 58:162-171, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  14. Accelerated repair and reduced mutagenicity of DNA damage induced by cigarette smoke in human bronchial cells transfected with E.coli formamidopyrimidine DNA glycosylase.

    Directory of Open Access Journals (Sweden)

    Mara Foresta

    Full Text Available Cigarette smoke (CS is associated to a number of pathologies including lung cancer. Its mutagenic and carcinogenic effects are partially linked to the presence of reactive oxygen species and polycyclic aromatic hydrocarbons (PAH inducing DNA damage. The bacterial DNA repair enzyme formamidopyrimidine DNA glycosylase (FPG repairs both oxidized bases and different types of bulky DNA adducts. We investigated in vitro whether FPG expression may enhance DNA repair of CS-damaged DNA and counteract the mutagenic effects of CS in human lung cells. NCI-H727 non small cell lung carcinoma cells were transfected with a plasmid vector expressing FPG fused to the Enhanced Green Fluorescent Protein (EGFP. Cells expressing the fusion protein EGFP-FPG displayed accelerated repair of adducts and DNA breaks induced by CS condensate. The mutant frequencies induced by low concentrations of CS condensate to the Na(+K(+-ATPase locus (oua(r were significantly reduced in cells expressing EGFP-FPG. Hence, expression of the bacterial DNA repair protein FPG stably protects human lung cells from the mutagenic effects of CS by improving cells' capacity to repair damaged DNA.

  15. Liability for on-site nuclear property damage

    International Nuclear Information System (INIS)

    Neems, H.J.

    2000-01-01

    Typically, liability for on-site property addressed in contracts between operator and its suppliers. Nuclear power plant operators ordinarily protect themselves against risk of nuclear damage to on-site property by insurance. Nuclear liability laws do not specifically address liability for nuclear damage to on-site property. Nuclear plant owners should address risk of damage to on-site property when developing risk management program

  16. On multi-site damage identification using single-site training data

    Science.gov (United States)

    Barthorpe, R. J.; Manson, G.; Worden, K.

    2017-11-01

    This paper proposes a methodology for developing multi-site damage location systems for engineering structures that can be trained using single-site damaged state data only. The methodology involves training a sequence of binary classifiers based upon single-site damage data and combining the developed classifiers into a robust multi-class damage locator. In this way, the multi-site damage identification problem may be decomposed into a sequence of binary decisions. In this paper Support Vector Classifiers are adopted as the means of making these binary decisions. The proposed methodology represents an advancement on the state of the art in the field of multi-site damage identification which require either: (1) full damaged state data from single- and multi-site damage cases or (2) the development of a physics-based model to make multi-site model predictions. The potential benefit of the proposed methodology is that a significantly reduced number of recorded damage states may be required in order to train a multi-site damage locator without recourse to physics-based model predictions. In this paper it is first demonstrated that Support Vector Classification represents an appropriate approach to the multi-site damage location problem, with methods for combining binary classifiers discussed. Next, the proposed methodology is demonstrated and evaluated through application to a real engineering structure - a Piper Tomahawk trainer aircraft wing - with its performance compared to classifiers trained using the full damaged-state dataset.

  17. New paradigms in the repair of oxidative damage in human genome: mechanisms ensuring repair of mutagenic base lesions during replication and involvement of accessory proteins.

    Science.gov (United States)

    Dutta, Arijit; Yang, Chunying; Sengupta, Shiladitya; Mitra, Sankar; Hegde, Muralidhar L

    2015-05-01

    Oxidized bases in the mammalian genome, which are invariably mutagenic due to their mispairing property, are continuously induced by endogenous reactive oxygen species and more abundantly after oxidative stress. Unlike bulky base adducts induced by UV and other environmental mutagens in the genome that block replicative DNA polymerases, oxidatively damaged bases such as 5-hydroxyuracil, produced by oxidative deamination of cytosine in the template strand, do not block replicative polymerases and thus need to be repaired prior to replication to prevent mutation. Following up our earlier studies, which showed that the Nei endonuclease VIII like 1 (NEIL1) DNA glycosylase, one of the five base excision repair (BER)-initiating enzymes in mammalian cells, has enhanced expression during the S-phase and higher affinity for replication fork-mimicking single-stranded (ss) DNA substrates, we recently provided direct experimental evidence for NEIL1's role in replicating template strand repair. The key requirement for this event, which we named as the 'cow-catcher' mechanism of pre-replicative BER, is NEIL1's non-productive binding (substrate binding without product formation) to the lesion base in ss DNA template to stall DNA synthesis, causing fork regression. Repair of the lesion in reannealed duplex is then carried out by NEIL1 in association with the DNA replication proteins. NEIL1 (and other BER-initiating enzymes) also interact with several accessory and non-canonical proteins including the heterogeneous nuclear ribonucleoprotein U and Y-box-binding protein 1 as well as high mobility group box 1 protein, whose precise roles in BER are still obscure. In this review, we have discussed the recent advances in our understanding of oxidative genome damage repair pathways with particular focus on the pre-replicative template strand repair and the role of scaffold factors like X-ray repairs cross-complementing protein 1 and poly (ADP-ribose) polymerase 1 and other accessory

  18. Human somatic, germinal and heritable mutagenicity

    International Nuclear Information System (INIS)

    Mendelsohn, M.L.

    1987-05-01

    This report deals with the general process of variant formation rather than with the consequences of a specific variant being present. It focusses on mutational mechanisms, mutagens, and the method for detecting de novo mutants and estimating mutation rate. It is to human genetics much like disease causation and prevention medicine are to medicine as a whole. The word ''mutagenicity'' is used in the title and throughout the text to connote the causation of all classes of genetic damage. Mutagenicity and the corresponding words mutation, mutagen and mutagenesis can have multiple meaning, sometimes relating to gene mutation, sometimes to heritable mutation, and somtimes to all types of genetic damage. 38 refs., 1 tab

  19. Effect of site conditions on ground motion and damage

    Science.gov (United States)

    Borcherdt, R.; Glassmoyer, G.; Andrews, M.; Cranswick, E.

    1989-01-01

    Results of seismologic studies conducted by the U.S. reconnaissance team in conjunction with Soviet colleagues following the tragic earthquakes of December 7, 1988, suggest that site conditions may have been a major factor in contributing to increased damage levels in Leninakan. As the potential severity of these effects in Leninakan had not been previously identified, this chapter presents results intended to provide a preliminary quantification of these effects on both damage and levels of ground motion observed in Leninakan. The article describes the damage distribution geologic setting, ground motion amplification in Leninakan, including analog amplifications and spectral amplifications. Preliminary model estimates for site response are presented. It is concluded that ground motion amplification in the 0.5-2.5-second period range was a major contributing factor to increased damage in Leninakan as compared with Kirovakan. Leninakan is located on thick water saturated alluvial deposits.

  20. Base-repair substitutions alter the site-specific mutagenicity of UV and MNNG in the SUP4-o gene of the yeast

    International Nuclear Information System (INIS)

    Kunz, B.A.; Ayre, B.G.; Downes, A.M.T.; Kohalmi, S.E.; McMaster, C.R.; Peters, M.G.

    1989-01-01

    Yeast strains carrying SUP4-ogenes that habe base-pair substitutions at hotspots for UV or MNNG mutagenesis were treated with these agents. In both cases, the induced mutation frequencies were substantially reduced. Furthermore, specific substitutions at positions in SUP4-o that had not been mutated by MNNG resulted in the recovery of MNNG-induced mutations at these sites. These results demonstrate that base-pair identity is an important factor determining the site-specific mutagenicity of UV and MNNG in yeast. For UV, our findings suggest that the type of lesion that is induced, but not flanking DNA sequences, plays a role in specifying mutability at the sites examined. In contrast, DNA sequence context seems to be an important factor for MNNG mutagenesis. (author). 19 refs.; 3 tabs

  1. Physicochemical characteristics, mutagenicity and genotoxicity of airborne particles under industrial and rural influences in Northern Lebanon.

    Science.gov (United States)

    Melki, Pamela N; Ledoux, Frédéric; Aouad, Samer; Billet, Sylvain; El Khoury, Bilal; Landkocz, Yann; Abdel-Massih, Roula M; Courcot, Dominique

    2017-08-01

    In this work, the main objectives were to assess the mutagenic and genotoxic effects of fine particulate matter collected in an industrial influenced site in comparison with a non-industrial influenced one (rural site) and to relate the particulate matter (PM) composition to the observed genotoxic effects. At the industrial influenced site, higher concentrations of phosphates, trace metals, and polycyclic aromatic hydrocarbons (PAHs) in particles could be related to the contributions of quarries, fertilizer producer, cement plants, and tires burning. Gasoline and diesel combustion contributions were evidenced in particles collected at both sites. Particles collected under industrial influence showed a higher mutagenic potential on three tested strains of Salmonella typhimurium (TA98, YG1041, and TA102), and especially on the YG1041, compared to particles from the rural site. Furthermore, only particles collected in the vicinity of the industrial site showed a tendency to activate the SOS responses in Escherichia coli PQ37, which is indicative of DNA damage as a result of exposure of the bacteria cells to the action of mutagenic samples. The mutagenicity and genotoxicity of the industrial PM 2.5-0.3 particulates may be attributed to its composition especially in organic compounds. This study showed that proximity of industries can affect local PM composition as well as PM genotoxic and mutagenic potential.

  2. Mutagenicity, stable DNA adducts, and abasic sites induced in Salmonella by phenanthro[3,4-b]- and phenanthro[4,3-b]thiophenes, sulfur analogs of benzo[c]phenanthrene

    Energy Technology Data Exchange (ETDEWEB)

    Swartz, Carol D. [Department of Environmental Science and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); King, Leon C.; Nesnow, Stephen [Environmental Carcinogenesis Division, US Environmental Protection Agency, Research Triangle Park, NC, 27711 (United States); Umbach, David M. [Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of Health, DHHS, Research Triangle Park, NC 27709 (United States); Kumar, Subodh [Environmental Toxicology and Chemistry Laboratory, Great Lakes Center, State University of New York College at Buffalo, Buffalo, NY 14222 (United States); DeMarini, David M. [Environmental Carcinogenesis Division, US Environmental Protection Agency, Research Triangle Park, NC, 27711 (United States)], E-mail: demarini.david@epa.gov

    2009-02-10

    Sulfur-containing polycyclic aromatic hydrocarbons (thia-PAHs or thiaarenes) are common constituents of air pollution and cigarette smoke, but only a few have been studied for health effects. We evaluated the mutagenicity in Salmonella TA98, TA100, and TA104 of two sulfur-containing derivatives of benzo[c]phenanthrene, phenanthro[3,4-b]thiophene (P[3,4-b]T), and phenanthro[4,3-b]thiophene (P[4,3-b]T) as well as their dihydrodiol and sulfone derivatives. In addition, we assessed levels of stable DNA adducts (by {sup 32}P-postlabeling) as well as abasic sites (by an aldehydic-site assay) produced by six of these compounds in TA100. P[3,4-b]T and its 6,7- and 8,9-diols, P[3,4-b]T sulfone, P[4,3-b]T, and its 8,9-diol were mutagenic in TA100. P[3,4-b]T sulfone, the most potent mutagen, was approximately twice as potent as benzo[a]pyrene in both TA98 and TA100. Benzo-ring dihydrodiols were much more potent than K-region dihydrodiols, which had little or no mutagenic activity in any strain. P[3,4-b]T sulfone produced abasic sites and not stable DNA adducts; the other five compounds examined, B[c]P, B[c]P 3,4-diol, P[3,4-b]T, P[3,4-b]T 8,9-diol, and P[4,3-b]T 8,9-diol, produced only stable DNA adducts. P[3,4-b]T sulfone was the only compound that produced significant levels of frameshift mutagenicity and induced mutations primarily at GC sites. In contrast, B[c]P, its 3,4-diol, and the 8,9 diols of the phenanthrothiophenes induced mutations primarily at AT sites. P[3,4-b]T was not mutagenic in TA104, whereas P[3,4-b]T sulfone was. The two isomeric forms (P[3,4-b]T and P[4,3-b]T) are apparently activated differently, with the latter, but not the former, involving a diol pathway. This study is the first illustrating the potential importance of abasic sites in the mutagenicity of thia-PAHs.

  3. Investigations on potential co-mutagenic effects of formaldehyde

    Energy Technology Data Exchange (ETDEWEB)

    Speit, Günter, E-mail: guenter.speit@uni-ulm.de; Linsenmeyer, Regina; Duong, Giang; Bausinger, Julia

    2014-02-15

    Highlights: • A549 cells were exposed to formaldehyde in combination with various mutagens. • Formaldehyde did not affect the induction and removal of DNA damage (comet assay). • Formaldehyde did not affect the induction of micronuclei by the mutagens tested. • The expression of the O{sup 6}-methylguanine-DNA methyltransferase was not affected. - Abstract: The genotoxicity and mutagenicity of formaldehyde (FA) has been well-characterized during the last years. Besides its known direct DNA-damaging and mutagenic activity in sufficiently exposed cells, FA at low concentrations might also enhance the mutagenic and carcinogenic effects of other environmental mutagens by interfering with the repair of DNA lesions induced by these mutagens. To further assess potential co-mutagenic effects of FA, we exposed A549 human lung cells to FA in combination with various mutagens and measured the induction and removal of DNA damage by the comet assay and the production of chromosomal mutations by the cytokinesis-block micronucleus assay (CBMN assay). The mutagens tested were ionizing radiation (IR), (±)-anti-B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), N-nitroso-N-methylurea (methyl nitrosourea; MNU) and methyl methanesulfonate (MMS). FA (10–75 μM) did not enhance the genotoxic and mutagenic activity of these mutagens under the test conditions applied. FA alone and in combination with MNU or MMS did not affect the expression (mRNA level) of the gene of the O{sup 6}-methylguanine-DNA methyltransferase (MGMT) in A549 cells. The results of these experiments do not support the assumption that low FA concentrations might interfere with the repair of DNA damage induced by other mutagens.

  4. Mutagenic DNA repair in enterobacteria

    International Nuclear Information System (INIS)

    Sedgwick, S.G.; Chao Ho; Woodgate, R.

    1991-01-01

    Sixteen species of enterobacteria have been screened for mutagenic DNA repair activity. In Escherichia coli, mutagenic DNA repair is encoded by the umuDC operon. Synthesis of UmuD and UmuC proteins is induced as part of the SOS response to DNA damage, and after induction, the UmuD protein undergoes an autocatalytic cleavage to produce the carboxy-terminal UmuD' fragment needed for induced mutagenesis. The presence of a similar system in other species was examined by using a combined approach of inducible-mutagenesis assays, cross-reactivity to E. coli UmuD and UmuD' antibodies to test for induction and cleavage of UmuD-like proteins, and hybridization with E. coli and Salmonella typhimurium u mu DNA probes to map umu-like genes. The results indicate a more widespread distribution of mutagenic DNA repair in other species than was previously thought. They also show that umu loci can be more complex in other species than in E. coli. Differences in UV-induced mutability of more than 200-fold were seen between different species of enteric bacteria and even between multiple natural isolates of E. coli, and yet some of the species which display a poorly mutable phenotype still have umu-like genes and proteins. It is suggested that umuDC genes can be curtailed in their mutagenic activities but that they may still participate in some other, unknown process which provides the continued stimulus for their retention

  5. Induced mutations in chickpea (Cicer arietinum L.) I. comparative mutagenic effectiveness and efficiency of physical & chemical mutagens

    International Nuclear Information System (INIS)

    Kharkwal, M.C.

    1998-01-01

    Mutagenic effectiveness usually means the rate of mutation as related to dose. Mutagenic efficiency refers to the mutation rate in relation to damage. Studies on comparative mutagenic effectiveness and efficiency of two physical (gamma rays and fast neutrons) and two chemical mutagens (NMU and EMS) on two desi (G 130 & H 214), one kabuli (C 104) and one green seeded (L 345) chickpea (Cicer arietinum L.) have been reported. The treatments included three doses each of gamma rays (400, 500 and 600 Gy) and fast neutrons (5, 10 and 15 Gy) and two concentrations with two different durations of two chemical mutagens, NMU 0.01% 20h and 0.02% 8h) and EMS (0.1% 20h and 0.2% 8h). Results indicated that chemical mutagens, particularly NMU are not only more effective but also efficient than physical mutagens in inducing mutations in chickpea. Mutagenic effectiveness and efficiency showed differential behaviour depending upon mutagen and varietal type. Chemical mutagens were more efficient than physical in inducing cholorophyll as well as viable and total number of mutations. Among the mutagens NMU was the most potent, while in the physical, gamma rays were more effective. Out of four mutagens, NMU was the most effective and efficient in inducing a high frequency and wide spectrum of chlorophyll mutations in the M2 followed by fast neutrons. While gamma rays showed least effectiveness, EMS was least efficient mutagens. Major differences in the mutagenic response of the four cultivars were observed. The varieties of desi type were more resistant towards mutagenic treatment than kabuli and green seeded type

  6. Oxidative Damage and Mutagenic Potency of Fast Neutron and UV-B Radiation in Pollen Mother Cells and Seed Yield of Vicia faba L.

    Directory of Open Access Journals (Sweden)

    Ekram Abdel Haliem

    2013-01-01

    Full Text Available In recent years, there has been a great deal of attention toward free radicals, reactive oxygen species (ROS generated by exposure of crop plant cells to physical radiations. Henceforth, the current study was planned to compare oxidative stress and mutagenic potential of different irradiation doses of fast neutron (FN and UV-B on meiotic-pollen mother cells (PMCs, pollen grains (PGs and seeds yielded from irradiated faba beans seedlings. On the cytogenetic level, each irradiation type had special interference with DNA of PMC and exhibited wide range of mutagenic action on the frequency and type of chromosomal anomalies, fertility of PGs and seed yield productivity based on the irradiation exposure dose and radiation sensitivity of faba bean plants compared with un-irradiated ones. On the molecular level, SDS-PAGE and RPAD-PCR analyses of seeds yielded from irradiated seedlings exhibited distinctive polymorphisms based on size, intensity, appearance, and disappearance of polypeptides bands compared with un-irradiated ones. The total values of protein and DNA polymorphisms reached 88% and 90.80% respectively. The neutron fluency (2.3 × 106 n/cm2 and UV-B dose for 1 hr were recorded as bio-positive effects. The present study proved that genetic variations revealed by cytogenetic test could be supported by gene expression (alterations in RAPD and protein profiles.

  7. A risk assessment method for multi-site damage

    Science.gov (United States)

    Millwater, Harry Russell, Jr.

    This research focused on developing probabilistic methods suitable for computing small probabilities of failure, e.g., 10sp{-6}, of structures subject to multi-site damage (MSD). MSD is defined as the simultaneous development of fatigue cracks at multiple sites in the same structural element such that the fatigue cracks may coalesce to form one large crack. MSD is modeled as an array of collinear cracks with random initial crack lengths with the centers of the initial cracks spaced uniformly apart. The data used was chosen to be representative of aluminum structures. The structure is considered failed whenever any two adjacent cracks link up. A fatigue computer model is developed that can accurately and efficiently grow a collinear array of arbitrary length cracks from initial size until failure. An algorithm is developed to compute the stress intensity factors of all cracks considering all interaction effects. The probability of failure of two to 100 cracks is studied. Lower bounds on the probability of failure are developed based upon the probability of the largest crack exceeding a critical crack size. The critical crack size is based on the initial crack size that will grow across the ligament when the neighboring crack has zero length. The probability is evaluated using extreme value theory. An upper bound is based on the probability of the maximum sum of initial cracks being greater than a critical crack size. A weakest link sampling approach is developed that can accurately and efficiently compute small probabilities of failure. This methodology is based on predicting the weakest link, i.e., the two cracks to link up first, for a realization of initial crack sizes, and computing the cycles-to-failure using these two cracks. Criteria to determine the weakest link are discussed. Probability results using the weakest link sampling method are compared to Monte Carlo-based benchmark results. The results indicate that very small probabilities can be computed

  8. Probability of growth of small damage sites on the exit surface of fused silica optics.

    Science.gov (United States)

    Negres, Raluca A; Abdulla, Ghaleb M; Cross, David A; Liao, Zhi M; Carr, Christopher W

    2012-06-04

    Growth of laser damage on fused silica optical components depends on several key parameters including laser fluence, wavelength, pulse duration, and site size. Here we investigate the growth behavior of small damage sites on the exit surface of SiO₂ optics under exposure to tightly controlled laser pulses. Results demonstrate that the onset of damage growth is not governed by a threshold, but is probabilistic in nature and depends both on the current size of a damage site and the laser fluence to which it is exposed. We also develop models for use in growth prediction. In addition, we show that laser exposure history also influences the behavior of individual sites.

  9. In vitro evaluation of mutagenicity and genotoxicity of sitagliptin ...

    African Journals Online (AJOL)

    Keywords: Sitagliptin, Artificial sweeteners, Comet assay, DNA damage, Ames assay, Genotoxicity,. Mutagenicity. Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus,. International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index Copernicus, EBSCO, African.

  10. Molecular and genetic mechanisms of environmental mutagens

    International Nuclear Information System (INIS)

    Kubitschek, H.E.; Derstine, P.L.; Griego, V.M.; Matsushita, T.; Peak, J.G.; Peak, M.J.; Reynolds, P.R.; Webb, R.B.; Williams-Hill, D.

    1981-01-01

    This program is primarily concerned with elucidation of the nature of DNA lesions produced by environmental and energy related mutagens, their mechanisms of action, and their repair. The main focus is on actions of chemical mutagens and electromagnetic radiations. Synergistic interactions between mutagens and the mutational processes that lead to synergism are being investigated. Mutagens are chosen for study on the basis of their potential for analysis of mutation (as genetic probes), for development of procedures for reducing mutational damage, for their potential importance to risk assessment, and for development of improved mutagen testing systems. Bacterial cells are used because of the rapidity and clarity of scientific results that can be obtained, the detailed genetic maps, and the many well-defined mutand strains available. The conventional tools of microbial and molecular genetics are used, along with intercomparison of genetically related strains. Advantage is taken of tcollective dose commitment will result in more attention being paid to potential releases of radionuclides at relatively short times after disposal

  11. A method for estimating the local area economic damages of Superfund waste sites

    International Nuclear Information System (INIS)

    Walker, D.R.

    1992-01-01

    National Priority List (NPL) sites, or more commonly called Superfund sites, are hazardous waste sites (HWS) deemed by the Environmental Protection Agency (EPA) to impose the greatest risks to human health or welfare or to the environment. HWS are placed and ranked for cleanup on the NPL based on a score derived from the Hazard Ranking System (HRS), which is a scientific assessment of the health and environmental risks posed by HWS. A concern of the HRS is that the rank of sites is not based on benefit-cost analysis. The main objective of this dissertation is to develop a method for estimating the local area economic damages associated with Superfund waste sites. Secondarily, the model is used to derive county-level damage estimates for use in ranking the county level damages from Superfund sites. The conceptual model used to describe the damages associated with Superfund sites is a household-firm location decision model. In this model assumes that households and firms make their location choice based on the local level of wages, rents and amenities. The model was empirically implemented using 1980 census microdata on households and workers in 253 counties across the US. The household sample includes data on the value and structural characteristics of homes. The worker sample includes the annual earnings of workers and a vector worker attributes. The microdata was combined with county level amenity data, including the number of Superfund sites. The hedonic pricing technique was used to estimate the effect of Superfund sites on average annual wages per household and on monthly expenditures on housing. The results show that Superfund sites impose statistically significant damages on households. The annual county damages from Superfund sites for a sample of 151 counties was over 14 billion dollars. The ranking of counties using the damage estimates is correlated with the rank of counties using the HRS

  12. Alkaline azide mutagenicity in cowpea

    Energy Technology Data Exchange (ETDEWEB)

    Mahna, S K; Bhargava, Anubha; Mohan, Lalit [Cytogenetics and Mycology Laboratory, Department of Botany, Government College, Ajmer (India)

    1990-07-01

    Sodium azide is known as a potent mutagen in cereals and legumes. It is very effective in acidic medium in barley. Here an attempt is made to measure the effectiveness of sodium azide in alkaline medium (pH 7.4) on cowpea (Vigna unguiculata (L.) Walp., variety FS-68). Seeds pre-soaked in distilled water for 5 hours were treated with different concentrations (10{sup -6}, 10{sup -5}, 10{sup -4} and 10{sup -3}M) of sodium azide (NaN{sub 3}) for 4 hours at 28{+-} 2 deg. C. Bottles were intermittently shaken, then the seeds were thoroughly washed in running tap water and subsequently planted in pots. The treatment caused significant biological damage such as reduction in seed germination, length of root and shoot, number of nodules and pods per plant and morphological leaf variations. Morphological, as well as chlorophyll mutants, were detected in M{sub 2}.

  13. Alkaline azide mutagenicity in cowpea

    International Nuclear Information System (INIS)

    Mahna, S.K.; Bhargava, Anubha; Mohan, Lalit

    1990-01-01

    Sodium azide is known as a potent mutagen in cereals and legumes. It is very effective in acidic medium in barley. Here an attempt is made to measure the effectiveness of sodium azide in alkaline medium (pH 7.4) on cowpea (Vigna unguiculata (L.) Walp., variety FS-68). Seeds pre-soaked in distilled water for 5 hours were treated with different concentrations (10 -6 , 10 -5 , 10 -4 and 10 -3 M) of sodium azide (NaN 3 ) for 4 hours at 28± 2 deg. C. Bottles were intermittently shaken, then the seeds were thoroughly washed in running tap water and subsequently planted in pots. The treatment caused significant biological damage such as reduction in seed germination, length of root and shoot, number of nodules and pods per plant and morphological leaf variations. Morphological, as well as chlorophyll mutants, were detected in M 2

  14. Tornado damage at the Grand Gulf, Mississippi nuclear power plant site: aerial and ground surveys

    International Nuclear Information System (INIS)

    Fujita, T.T.; McDonald, J.R.

    1978-05-01

    A tornado struck the Grand Gulf nuclear power generating station, Port Gibson, Mississippi, about 11:30 p.m. on April 17, 1978. Storm damage investigators from the University of Chicago and Texas Tech University were dispatched to survey the damage. The meteorological situation that spawned the Grand Gulf tornado and seven others in the area is discussed. Aerial surveys of the entire damage path and detailed surveys of the plant site are presented. An engineering evaluation of the damage is also presented based primarily on information gained from detailed ground surveys

  15. Stalled repair of lesions when present within a clustered DNA damage site

    International Nuclear Information System (INIS)

    Lomax, M.E.; Cunniffe, S.; O'Neill, P.

    2003-01-01

    Ionising radiation produces clustered DNA damages (two or more lesions within one or two helical turns of the DNA) which could challenge the repair mechanism(s) of the cell. Using purified base excision repair (BER) enzymes and synthetic oligonucleotides a number of recent studies have established the excision of a lesion within clustered damage sites is compromised. Evidence will be presented that the efficiency of repair of lesions within a clustered DNA damage site is reduced, relative to that of the isolated lesions, since the lifetime of both lesions is extended by up to four fold. Simple clustered damage sites, comprised of single-strand breaks, abasic sites and base damages, one or five bases 3' or 5' to each other, were synthesised in oligonucleotides and repair carried out in mammalian cell nuclear extracts. The rate of repair of the single-strand break/abasic site within these clustered damage sites is reduced, mainly due to inhibition of the DNA ligase. The mechanism of repair of the single-strand break/abasic site shows some asymmetry. Repair appears to be by the short-patch BER pathway when the lesions are 5' to each other. In contrast, when the lesions are 3' to each other repair appears to proceed along the long-patch BER pathway. The lesions within the cluster are processed sequentially, the single-strand break/abasic site being repaired before excision of 8-oxoG, limiting the formation of double-strand breaks to <2%. Stalled processing of clustered DNA damage extends the lifetime of the lesions to an extent that could have biological consequences, e.g. if the lesions are still present during transcription and/or at replication mutations could arise

  16. Hanford Site Tank 241-SY-101, damaged equipment removal

    International Nuclear Information System (INIS)

    Titzler, P.A.; Legare, D.E.; Barrus, H.G.

    1993-11-01

    Hanford Site Tank 241-SY-101 has a history of generating hydrogen-nitrous oxide gases. The gases are generated and trapped in the non-convective waste layer near the bottom of the 23-m- (75-ft-) diameter underground tank. Approximately every three months the pressure in the tank is relieved as the trapped gases are released through or around the surface crust into the tank dome. This process moves large amounts of liquid waste and crust material around in the tank. The moving waste displaced air lances and thermocouple assemblies (2-in. schedule-40 pipe) installed in four tank risers and permanently bent them to a maximum angle of 40 degrees. The bends were so severe that assemblies could not be removed from the tank using the originally designed hardware. Just after the tank releases the trapped gas, a 20-to-30-day work ''window'' opens

  17. A methodology for assessing the impact of mutagens on aquatic ecosystems. Final report

    International Nuclear Information System (INIS)

    Knezovich, J.P.; Martinelli, R.E.

    1995-03-01

    Assessments of impacts of hazardous agents (i.e., chemical and physical mutagens) on human health have focused on defining the effects of chronic exposure on individuals, with cancer being the main effect of concern. In contrast, impacts on ecosystems have traditionally been gauged by the assessment of near-term organism mortality, which is clearly not a useful endpoint for assessing the long-term effects of chronic exposures. Impacts on individual organisms that affect the long-term survival of populations are much more important but are also more difficult to define. Therefore, methods that provide accurate measures of sub-lethal effects that are linked to population survival are required so that accurate assessments of environmental damage can be made and remediation efforts, if required, can be initiated. Radioactive substances have entered aquatic environments as a result of research and production activities, intentional disposal, and accidental discharges. At several DOE sites, surface waters and sediments are contaminated with radioactive and mutagenic materials. The accident at the Chernobyl power station in the former Soviet Union (FSU) has resulted in the contamination of biota present in the Kiev Reservoir. This documents presents a methodology which addresses the effects of a direct-acting mutagen (radiation) on aquantic organisms by applying sensitive techniques for assessing damage to genetic material

  18. Dietary phenolics as anti-mutagens and inhibitors of tobacco-related DNA adduction in the urothelium of smokers.

    Science.gov (United States)

    Malaveille, C; Hautefeuille, A; Pignatelli, B; Talaska, G; Vineis, P; Bartsch, H

    1996-10-01

    Human urine is known to contain substances that strongly inhibit bacterial mutagenicity of aromatic and heterocyclic amines in vitro. The biological relevance of these anti-mutagens was examined by comparing levels of tobacco-related DNA adducts in exfoliated urothelial cells from smokers with the anti-mutagenic activity in corresponding 24-h urine samples. An inverse relationship was found between the inhibition of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-mutagenicity by urine extracts in vitro and two DNA adduct measurements: the level of the putatively identified N-(deoxyguanosine-8-yl)-4-aminobiphenyl adduct and the total level of all tobacco-smoke-related carcinogen adducts including those probably derived from PhIP. Urinary anti-mutagenicity in vitro appears thus to be a good indicator of the anti-genotoxicity exerted by substances excreted in urine, that protect the bladder mucosal cells (and possibly other cells) against DNA damage. These substances appear to be dietary phenolics and/or their metabolites because (i) the anti-mutagenic activity of urine extracts (n = 18) was linearly related to their content in phenolics; (ii) the concentration ranges of these substances in urine extracts were similar to those of various plant phenols (quercetin, isorhamnetin and naringenin) for which an inhibitory effect on the liver S9-mediated mutagenicity of PhIP was obtained; (iii) treatment of urines with beta-glucuronidase and arylsulfatase enhanced both anti-mutagenicity and the levels of phenolics in urinary extracts; (iv) urinary extracts inhibited noncompetitively the liver S9-mediated mutagenicity of PhIP as did quercetin, used as a model phenolics. Several structural features of the flavonoids were identified as necessary for the inhibition of PhIP and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxiline mutagenicity. Fractionation by reverse-phase HPLC and subsequent analysis of two urinary extracts, showed the presence of several anti-mutagenic

  19. Mutagenicity of complex mixtures

    International Nuclear Information System (INIS)

    Pelroy, R.A.

    1985-01-01

    The effect of coal-derived complex chemical mixtures on the mutagenicity of 6-aminochrysene (6-AC) was determined with Salmonella typhimurium TA98. Previous results suggested that the mutagenic potency of 6-AC for TA98 in the standard microsomal activation (Ames) assay increased if it was presented to the cells mixed with high-boiling coal liquids (CL) from the solvent refined coal (SRC) process. In this year's work, the apparent mutational synergism of CL and 6-AC was independently verified in a fluctuation bioassay which allowed quantitation of mutational frequencies and cell viability. The results of this assay system were similar to those in the Ames assay. Moreover, the fluctation assay revealed that mutagenesis and cellular toxicity induced by 6-AC were both strongly enhanced if 6-AC was presented to the cells mixed in a high-boiling CL. 4 figures

  20. A contribution to the study on the mutagenicity of atmospheres

    International Nuclear Information System (INIS)

    Blaise, Philipp

    1986-01-01

    Following a review of the literature, the genotoxic hazards of atmospheric pollutants at various locations (rural sites, motorway tolls, paint shops...) were evaluated by in vitro mutagenicity assays (Ames' test and SOS chromo-test) and analytical methods (gas chromatography and mass spectrometry). Instrumentation and procedures were developed for the sampling of volatile organic pollutants: adsorption on XAD 2 followed by acetone extraction of the compounds trapped. A comparative study allowed to assess the relative mutagenic action of the volatile organic compounds and to establish a mutagenicity scale. (author) [fr

  1. Incident laser modulation of a repaired damage site with a rim in fused silica rear subsurface

    Institute of Scientific and Technical Information of China (English)

    Li Li; Xiang Xia; Zu Xiao-Tao; Yuan Xiao-Dong; He Shao-Bo; Jiang Xiao-Dong; Zheng Wan-Guo

    2012-01-01

    Local CO2 laser treatment has proved to be an effective method to prevent the 351-nm laser-induced damage sitesin a fused silica surface from exponentially growing,which is responsible for limiting the lifetime of optics in high fluence laser systems.However,the CO2 laser induced ablation crater is often surrounded by a raised rim at the edge,which can also result in the intensification of transmitted ultraviolet light that may damage the downstream optics.In this work,the three-dimensional finite-difference time-domain method is developed to simulate the distribution of electrical field intensity in the vicinity of the CO2 laser mitigated damage site located in the exit subsurface of fused silica.The simulated results show that the repaired damage sites with raised rims cause more notable modulation to the incident laser than those without rims.Specifically,we present a theoretical model of using dimpled patterning to control the rim structure around the edge of repaired damage sites to avoid damage to downstream optics.The calculated results accord well with previous experimental results and the underlying physical mechanism is analysed in detail.

  2. AN OVERVIEW OF MUTAGENIC POTENTIAL OF PESTICIDES

    Directory of Open Access Journals (Sweden)

    Aurel Popescu

    2013-12-01

    Full Text Available This paper presents a synthesis of mutagenic potential of a few pesticides. Cytotoxicity tests, using plant test systems in vivo, such as Allium cepa, are validated by the similar results performed in animal testing in vitro. Cytogenetic tests are usefulness for identifying and evaluating the damaging effects of pesticides present in various concentrations under different exposure times on living organisms. Mutagenic potential of different pesticides used can be detected cytologically by cellular inhibition (mitotic index and replication index are used as indicators of adequate cell proliferation, disruption in metaphase, induction of chromosomal aberrations, numerical and structural, ranging from chromosomal fragmentation to the disorganization of the mitotic spindle, and consequently of all subsequent dependent mitotic phases.

  3. Structure-Activity Relationship Models for Rat Carcinogenesis and Assessing the Role Mutagens Play in Model Predictivity

    Science.gov (United States)

    Carrasquer, C. Alex; Batey, Kaylind; Qamar, Shahid; Cunningham, Albert R.; Cunningham, Suzanne L.

    2016-01-01

    We previously demonstrated that fragment based cat-SAR carcinogenesis models consisting solely of mutagenic or non-mutagenic carcinogens varied greatly in terms of their predictive accuracy. This led us to investigate how well the rat cancer cat-SAR model predicted mutagens and non-mutagens in their learning set. Four rat cancer cat-SAR models were developed: Complete Rat, Transgender Rat, Male Rat, and Female Rat, with leave-one-out (LOO) validation concordance values of 69%, 74%, 67%, and 73%, respectively. The mutagenic carcinogens produced concordance values in the range of 69–76% as compared to only 47–53% for non-mutagenic carcinogens. As a surrogate for mutagenicity comparisons between single site and multiple site carcinogen SAR models was analyzed. The LOO concordance values for models consisting of 1-site, 2-site, and 4+-site carcinogens were 66%, 71%, and 79%, respectively. As expected, the proportion of mutagens to non-mutagens also increased, rising from 54% for 1-site to 80% for 4+-site carcinogens. This study demonstrates that mutagenic chemicals, in both SAR learning sets and test sets, are influential in assessing model accuracy. This suggests that SAR models for carcinogens may require a two-step process in which mutagenicity is first determined before carcinogenicity can be accurately predicted. PMID:24697549

  4. Satellite imagery-based monitoring of archaeological site damage in the Syrian civil war.

    Science.gov (United States)

    Casana, Jesse; Laugier, Elise Jakoby

    2017-01-01

    Since the start of the Syrian civil war in 2011, the rich archaeological heritage of Syria and northern Iraq has faced severe threats, including looting, combat-related damage, and intentional demolition of monuments. However, the inaccessibility of the conflict zone to archaeologists or cultural heritage specialists has made it difficult to produce accurate damage assessments, impeding efforts to develop mitigation strategies and policies. This paper presents results of a project, undertaken in collaboration with the American Schools of Oriental Research (ASOR) and the US Department of State, to monitor damage to archaeological sites in Syria, northern Iraq, and southern Turkey using recent, high-resolution satellite imagery. Leveraging a large database of archaeological and heritage sites throughout the region, as well as access to continually updated satellite imagery from DigitalGlobe, this project has developed a flexible and efficient methodology to log observations of damage in a manner that facilitates spatial and temporal queries. With nearly 5000 sites carefully evaluated, analysis reveals unexpected patterns in the timing, severity, and location of damage, helping us to better understand the evolving cultural heritage crisis in Syria and Iraq. Results also offer a model for future remote sensing-based archaeological and heritage monitoring efforts in the Middle East and beyond.

  5. Satellite imagery-based monitoring of archaeological site damage in the Syrian civil war.

    Directory of Open Access Journals (Sweden)

    Jesse Casana

    Full Text Available Since the start of the Syrian civil war in 2011, the rich archaeological heritage of Syria and northern Iraq has faced severe threats, including looting, combat-related damage, and intentional demolition of monuments. However, the inaccessibility of the conflict zone to archaeologists or cultural heritage specialists has made it difficult to produce accurate damage assessments, impeding efforts to develop mitigation strategies and policies. This paper presents results of a project, undertaken in collaboration with the American Schools of Oriental Research (ASOR and the US Department of State, to monitor damage to archaeological sites in Syria, northern Iraq, and southern Turkey using recent, high-resolution satellite imagery. Leveraging a large database of archaeological and heritage sites throughout the region, as well as access to continually updated satellite imagery from DigitalGlobe, this project has developed a flexible and efficient methodology to log observations of damage in a manner that facilitates spatial and temporal queries. With nearly 5000 sites carefully evaluated, analysis reveals unexpected patterns in the timing, severity, and location of damage, helping us to better understand the evolving cultural heritage crisis in Syria and Iraq. Results also offer a model for future remote sensing-based archaeological and heritage monitoring efforts in the Middle East and beyond.

  6. The detection and analysis of mutagens: Final report, 1968--1986

    International Nuclear Information System (INIS)

    Ames, B.N.

    1989-01-01

    Our main objectives are: to develop and improve the Salmonella test for detecting environmental mutagens; to investigate the relationship between carcinogens and mutagens and to validate the Salmonella test for detecting carcinogens; to uncover significant unsuspected environmental mutagens/carcinogens; to investigate the theory of mutagenesis; to develop new methods for determining DNA damage by particular chemicals in individual people; to understand the role of oxygen radicals in DNA damage, cancer, and aging; and to investigate the role of anti-carcinogens in preventing DNA damage

  7. Recruitment of RNA polymerase II cofactor PC4 to DNA damage sites

    Science.gov (United States)

    Mortusewicz, Oliver; Roth, Wera; Li, Na; Cardoso, M. Cristina; Meisterernst, Michael; Leonhardt, Heinrich

    2008-01-01

    The multifunctional nuclear protein positive cofactor 4 (PC4) is involved in various cellular processes including transcription, replication, and chromatin organization. Recently, PC4 has been identified as a suppressor of oxidative mutagenesis in Escherichia coli and Saccharomyces cerevisiae. To investigate a potential role of PC4 in mammalian DNA repair, we used a combination of live cell microscopy, microirradiation, and fluorescence recovery after photobleaching analysis. We found a clear accumulation of endogenous PC4 at DNA damage sites introduced by either chemical agents or laser microirradiation. Using fluorescent fusion proteins and specific mutants, we demonstrated that the rapid recruitment of PC4 to laser-induced DNA damage sites is independent of poly(ADP-ribosyl)ation and γH2AX but depends on its single strand binding capacity. Furthermore, PC4 showed a high turnover at DNA damages sites compared with the repair factors replication protein A and proliferating cell nuclear antigen. We propose that PC4 plays a role in the early response to DNA damage by recognizing single-stranded DNA and may thus initiate or facilitate the subsequent steps of DNA repair. PMID:19047459

  8. New elements of molecular orchestra at radiation-induced damaged genomic sites

    International Nuclear Information System (INIS)

    Wani, Altaf A.; Battu, Aruna; Ray, Alo

    2012-01-01

    DNA damage promptly activates cell cycle checkpoints enabling cells to repair their genome. ATR and ATM kinases are central to the checkpoint activation in response to DNA damage and replication stress. Activated ATR and ATM phosphorylate several downstream proteins involved in DNA repair and cell cycle arrest. However, the nature of the signal, which initially activates these kinases in response to UV damage and how they interact with nucleotide excision repair (NER) pathway, is unclear. Our research has shown that DDB2 and XPC, two early damage recognition factors, promoted ATR and ATM recruitment and phosphorylation. ATR and ATM localized to the damage site and physically interact with XPC. ATR and ATM recruitment and their phosphorylation is negatively affected in cells defective in DDB2 and XPC functions while conversely ATR- and ATM-deficiency fail to influence the damage recruitment of DDB2 and XPC proteins. Consequently, the phosphorylation of ATR and ATM substrates, Chk1, Chk2, H2AX, and BRCA1 is significantly reduced or abrogated in mutant cells, indicating that defective DDB2 and XPC function impaired the checkpoint signal transduction cascade in response to UV damage. DDB2 and XPC also regulated the BRCA1 and Rad51 recruitment to the damage site, implicating their role in homologous recombination-mediated DNA repair pathway. Supporting data reveal that the depletion of ATR and ATM influenced the NER efficiency. Moreover, upon completion of NER, ordered restoration of chromatin structure and key epigenetic marks are necessary for resumption of the cell's normal function. We have demonstrated such a restoration role of H3K56 acetylation (H3K56Ac) mark in response to UV irradiation, In human cells a fast initial deacetylation of H3K56 is followed by full renewal of an acetylated state at ∼ 24-48 hr post-irradiation. Histone chaperone, anti-silencing function-1A (ASF1A), is crucial for post-repair H3K56Ac restoration, which in turn, is needed for the

  9. Spontaneous mutation by mutagenic repair of spontaneous lesions in DNA

    International Nuclear Information System (INIS)

    Hastings, P.J.; Quah, S.-K.; Borstel, R.C. von

    1976-01-01

    It is stated that strains of yeast carrying mutations in many of the steps in pathways repairing radiation-induced damage to DNA have enhanced spontaneous mutation rates. Most strains isolated because they have enhanced spontaneous mutation carry mutations in DNA repair systems. This suggests that much spontaneous mutation arises by mutagenic repair of spontaneous lesions. (author)

  10. Mutagenic potentials of crataegus and laxaricin in human blood ...

    African Journals Online (AJOL)

    Single cell gel electrophoresis (SCGE) or comet assay was introduced as a microelectrophoretic method for direct visualization of DNA damage in individual cells. Green plants in general contain mutagenic and carcinogenic substances, but there is little information. Due to the increased use and availability of herbal ...

  11. Codon cassette mutagenesis: a general method to insert or replace individual codons by using universal mutagenic cassettes.

    OpenAIRE

    Kegler-Ebo, D M; Docktor, C M; DiMaio, D

    1994-01-01

    We describe codon cassette mutagenesis, a simple method of mutagenesis that uses universal mutagenic cassettes to deposit single codons at specific sites in double-stranded DNA. A target molecule is first constructed that contains a blunt, double-strand break at the site targeted for mutagenesis. A double-stranded mutagenic codon cassette is then inserted at the target site. Each mutagenic codon cassette contains a three base pair direct terminal repeat and two head-to-head recognition sequen...

  12. A high-throughput and quantitative method to assess the mutagenic potential of translesion DNA synthesis

    Science.gov (United States)

    Taggart, David J.; Camerlengo, Terry L.; Harrison, Jason K.; Sherrer, Shanen M.; Kshetry, Ajay K.; Taylor, John-Stephen; Huang, Kun; Suo, Zucai

    2013-01-01

    Cellular genomes are constantly damaged by endogenous and exogenous agents that covalently and structurally modify DNA to produce DNA lesions. Although most lesions are mended by various DNA repair pathways in vivo, a significant number of damage sites persist during genomic replication. Our understanding of the mutagenic outcomes derived from these unrepaired DNA lesions has been hindered by the low throughput of existing sequencing methods. Therefore, we have developed a cost-effective high-throughput short oligonucleotide sequencing assay that uses next-generation DNA sequencing technology for the assessment of the mutagenic profiles of translesion DNA synthesis catalyzed by any error-prone DNA polymerase. The vast amount of sequencing data produced were aligned and quantified by using our novel software. As an example, the high-throughput short oligonucleotide sequencing assay was used to analyze the types and frequencies of mutations upstream, downstream and at a site-specifically placed cis–syn thymidine–thymidine dimer generated individually by three lesion-bypass human Y-family DNA polymerases. PMID:23470999

  13. Biological consequences of potential repair intermediates of clustered base damage site in Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Shikazono, Naoya, E-mail: shikazono.naoya@jaea.go.jp [Japan Atomic Energy Agency, Advanced Research Science Center, 2-4 Shirakata-Shirane, Tokai-mura, Naka-gun, Ibaraki 319-1195 (Japan); O' Neill, Peter [Gray Institute for Radiation Oncology and Biology, University of Oxford, Roosevelt Drive, Oxford OX3 7DQ (United Kingdom)

    2009-10-02

    Clustered DNA damage induced by a single radiation track is a unique feature of ionizing radiation. Using a plasmid-based assay in Escherichia coli, we previously found significantly higher mutation frequencies for bistranded clusters containing 7,8-dihydro-8-oxoguanine (8-oxoG) and 5,6-dihydrothymine (DHT) than for either a single 8-oxoG or a single DHT in wild type and in glycosylase-deficient strains of E. coli. This indicates that the removal of an 8-oxoG from a clustered damage site is most likely retarded compared to the removal of a single 8-oxoG. To gain further insights into the processing of bistranded base lesions, several potential repair intermediates following 8-oxoG removal were assessed. Clusters, such as DHT + apurinic/apyrimidinic (AP) and DHT + GAP have relatively low mutation frequencies, whereas clusters, such as AP + AP or GAP + AP, significantly reduce the number of transformed colonies, most probably through formation of a lethal double strand break (DSB). Bistranded AP sites placed 3' to each other with various interlesion distances also blocked replication. These results suggest that bistranded base lesions, i.e., single base lesions on each strand, but not clusters containing only AP sites and strand breaks, are repaired in a coordinated manner so that the formation of DSBs is avoided. We propose that, when either base lesion is initially excised from a bistranded base damage site, the remaining base lesion will only rarely be converted into an AP site or a single strand break in vivo.

  14. Biological consequences of potential repair intermediates of clustered base damage site in Escherichia coli

    International Nuclear Information System (INIS)

    Shikazono, Naoya; O'Neill, Peter

    2009-01-01

    Clustered DNA damage induced by a single radiation track is a unique feature of ionizing radiation. Using a plasmid-based assay in Escherichia coli, we previously found significantly higher mutation frequencies for bistranded clusters containing 7,8-dihydro-8-oxoguanine (8-oxoG) and 5,6-dihydrothymine (DHT) than for either a single 8-oxoG or a single DHT in wild type and in glycosylase-deficient strains of E. coli. This indicates that the removal of an 8-oxoG from a clustered damage site is most likely retarded compared to the removal of a single 8-oxoG. To gain further insights into the processing of bistranded base lesions, several potential repair intermediates following 8-oxoG removal were assessed. Clusters, such as DHT + apurinic/apyrimidinic (AP) and DHT + GAP have relatively low mutation frequencies, whereas clusters, such as AP + AP or GAP + AP, significantly reduce the number of transformed colonies, most probably through formation of a lethal double strand break (DSB). Bistranded AP sites placed 3' to each other with various interlesion distances also blocked replication. These results suggest that bistranded base lesions, i.e., single base lesions on each strand, but not clusters containing only AP sites and strand breaks, are repaired in a coordinated manner so that the formation of DSBs is avoided. We propose that, when either base lesion is initially excised from a bistranded base damage site, the remaining base lesion will only rarely be converted into an AP site or a single strand break in vivo.

  15. Direct detection and quantification of abasic sites for in vivo studies of DNA damage and repair

    International Nuclear Information System (INIS)

    Wang Yanming; Liu Lili; Wu Chunying; Bulgar, Alina; Somoza, Eduardo; Zhu Wenxia; Gerson, Stanton L.

    2009-01-01

    Use of chemotherapeutic agents to induce cytotoxic DNA damage and programmed cell death is a key strategy in cancer treatments. However, the efficacy of DNA-targeted agents such as temozolomide is often compromised by intrinsic cellular responses such as DNA base excision repair (BER). Previous studies have shown that BER pathway resulted in formation of abasic or apurinic/apyrimidinic (AP) sites, and blockage of AP sites led to a significant enhancement of drug sensitivity due to reduction of DNA base excision repair. Since a number of chemotherapeutic agents also induce formation of AP sites, monitoring of these sites as a clinical correlate of drug effect will provide a useful tool in the development of DNA-targeted chemotherapies aimed at blocking abasic sites from repair. Here we report an imaging technique based on positron emission tomography (PET) that allows for direct quantification of AP sites in vivo. For this purpose, positron-emitting carbon-11 has been incorporated into methoxyamine ([ 11 C]MX) that binds covalently to AP sites with high specificity. The binding specificity of [ 11 C]MX for AP sites was demonstrated by in vivo blocking experiments. Using [ 11 C]MX as a radiotracer, animal PET studies have been conducted in melanoma and glioma xenografts for quantification of AP sites. Following induction of AP sites by temozolomide, both tumor models showed significant increase of [ 11 C]MX uptake in tumor regions in terms of radioactivity concentration as a function of time, which correlates well with conventional aldehyde reactive probe (ARP)-based bioassays for AP sites.

  16. Handbook of mutagenicity test procedures

    International Nuclear Information System (INIS)

    Kilbey, B.J.; Legatov, M.

    1977-01-01

    27 articles are presented on particular techniques of mutagen testing. Background information is given in materials, experimental design, pitfalls and difficults, to enable the reader to perform these tests with minimal additional help. Also included is the use of data from population records, the handling and safety aspects of mutagens and carcinogens and some of the basic statistical concepts to be borne in mind when mutation experiments are designed. (C.F.)

  17. Absence of mutagenicity of plants used to treat gastrointestinal disorders

    Directory of Open Access Journals (Sweden)

    Santos F.V.

    2013-01-01

    Full Text Available The Brazilian Savanna (locally called “Cerrado” is an important biome presenting several plants that are used in popular medicine. However, the risks associated with the consumption of derivatives from these plants are generally unknown. Studies with compounds obtained from different species have shown the risks of DNA damage. The present work assessed the in vivo mutagenicity of three plant species used in popular medicine to treat human gastrointestinal disorders (Mouriri pusa, Qualea grandiflora and Qualea multiflora. The micronucleus assay was performed in peripheral blood of mice submitted to acute treatments. Results showed that no assessed extracts were mutagenic in vivo. In fact, the absence of mutagenicity in the present study indicates that the extracts do not contain compounds capable of inducing DNA breaks or chromosomal loss. However, further analysis should be performed in others systems to guarantee their safety, mainly to human chronic use.

  18. Histone peptide AKRHRK enhances H2O2-induced DNA damage and alters its site specificity

    International Nuclear Information System (INIS)

    Midorikawa, Kaoru; Murata, Mariko; Kawanishi, Shosuke

    2005-01-01

    Histone proteins are involved in compaction of DNA and the protection of cells from oxygen toxicity. However, several studies have demonstrated that the metal-binding histone reacts with H 2 O 2 , leading to oxidative damage to a nucleobase. We investigated whether histone can accelerate oxidative DNA damage, using a minimal model for the N-terminal tail of histone H4, CH 3 CO-AKRHRK-CONH 2 , which has a metal-binding site. This histone peptide enhanced DNA damage induced by H 2 O 2 and Cu(II), especially at cytosine residues, and induced additional DNA cleavage at the 5'-guanine of GGG sequences. The peptide also enhanced the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine and ESR spin-trapping signal from H 2 O 2 and Cu(II). Cyclic redox reactions involving histone-bound Cu(II) and H 2 O 2 , may give rise to multiple production of radicals leading to multiple hits in DNA. It is noteworthy that the histone H4 peptide with specific sequence AKRHRK can cause DNA damage rather than protection under metal-overloaded condition

  19. Analysis and prediction of Multiple-Site Damage (MSD) fatigue crack growth

    Science.gov (United States)

    Dawicke, D. S.; Newman, J. C., Jr.

    1992-08-01

    A technique was developed to calculate the stress intensity factor for multiple interacting cracks. The analysis was verified through comparison with accepted methods of calculating stress intensity factors. The technique was incorporated into a fatigue crack growth prediction model and used to predict the fatigue crack growth life for multiple-site damage (MSD). The analysis was verified through comparison with experiments conducted on uniaxially loaded flat panels with multiple cracks. Configuration with nearly equal and unequal crack distribution were examined. The fatigue crack growth predictions agreed within 20 percent of the experimental lives for all crack configurations considered.

  20. Analysis and prediction of Multiple-Site Damage (MSD) fatigue crack growth

    Science.gov (United States)

    Dawicke, D. S.; Newman, J. C., Jr.

    1992-01-01

    A technique was developed to calculate the stress intensity factor for multiple interacting cracks. The analysis was verified through comparison with accepted methods of calculating stress intensity factors. The technique was incorporated into a fatigue crack growth prediction model and used to predict the fatigue crack growth life for multiple-site damage (MSD). The analysis was verified through comparison with experiments conducted on uniaxially loaded flat panels with multiple cracks. Configuration with nearly equal and unequal crack distribution were examined. The fatigue crack growth predictions agreed within 20 percent of the experimental lives for all crack configurations considered.

  1. Time-dependent evolution of the excavation damaged zone in the argillaceous Tournemire site

    Energy Technology Data Exchange (ETDEWEB)

    Rejeb, A.; Cabrera, J. [Institut de Radioprotection et de Surete Nucleaire (IRSN/DEI/SARG), Lab. d' Etude Hydrodynamique et Geotechnique, 92 - Fontenay-aux-Roses (France)

    2006-07-01

    The experimental Tournemire site enables the assessment of the Excavation Damaged Zones (EDZ) around three structures excavated in argilites: the century-old tunnel, the ten year-old east and west galleries, and the three year-old main gallery. This paper discusses the main experimental results concerning the EDZ characterisation and their interpretation. EDZ fracture analyses from the galleries (cartography) and the radial boreholes (core analyses) allow for accurate structural characterisation of the EDZs. The tunnel has an EDZ with dense, homogeneous fracturing parallel to the wall, resembling onion skins. However, the new galleries do not have an EDZ similar to that of the tunnel. Unsaturated micro-cracks, mainly parallel to the bedding planes are observed on the non covered walls of each gallery. The extent of the EDZ does not seem to be affected by the age of the structure. It is approximately 20 % of the mean radius of the structure. Based on the modelling and experimental characterisation work completed, it is considered that the EDZ in this argillaceous Tournemire site is due to a deferred failure. At first time, when the wall of the structures are not covered the desaturation/re-saturation phenomena induced a tensile failure around the new galleries. During the time, these desaturation/re-saturation phenomena cause a gradual weakening of the material. The EDZ tunnel fractures are explained by this possible hydric damage and a decreasing mechanical strength with the time. These assumptions remain to be confirmed through coupled numerical modelling in unsaturated medium. (authors)

  2. Time-dependent evolution of the excavation damaged zone in the argillaceous Tournemire site

    International Nuclear Information System (INIS)

    Rejeb, A.; Cabrera, J.

    2006-01-01

    The experimental Tournemire site enables the assessment of the Excavation Damaged Zones (EDZ) around three structures excavated in argilites: the century-old tunnel, the ten year-old east and west galleries, and the three year-old main gallery. This paper discusses the main experimental results concerning the EDZ characterisation and their interpretation. EDZ fracture analyses from the galleries (cartography) and the radial boreholes (core analyses) allow for accurate structural characterisation of the EDZs. The tunnel has an EDZ with dense, homogeneous fracturing parallel to the wall, resembling onion skins. However, the new galleries do not have an EDZ similar to that of the tunnel. Unsaturated micro-cracks, mainly parallel to the bedding planes are observed on the non covered walls of each gallery. The extent of the EDZ does not seem to be affected by the age of the structure. It is approximately 20 % of the mean radius of the structure. Based on the modelling and experimental characterisation work completed, it is considered that the EDZ in this argillaceous Tournemire site is due to a deferred failure. At first time, when the wall of the structures are not covered the desaturation/re-saturation phenomena induced a tensile failure around the new galleries. During the time, these desaturation/re-saturation phenomena cause a gradual weakening of the material. The EDZ tunnel fractures are explained by this possible hydric damage and a decreasing mechanical strength with the time. These assumptions remain to be confirmed through coupled numerical modelling in unsaturated medium. (authors)

  3. Mutagenic activities of metal compounds in bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Nishioka, H

    1975-01-01

    Environmental contaminations by certain metal compounds are bringing about serious problems to human health, including genetic hazards. It has been reported that some compounds of iron, manganese and mercury induce point mutations in microorganisms. Also it has been observed that those of aluminum, antimony, arsenic, cadmium, lead and tellurium cause chromosome aberrations in plants, insects and cultured human cells. The mechanism of mutation induction by these metals remains, however, still obscure. For screening of chemical mutagens, Kada et al, recently developed a simple and efficient method named rec-assay by observing differential growth sensitivities to drugs in wild and recombination-deficient strains of Bacillus subtilis. When a chemical is more inhibitory for Rec/sup -/ than for Rec/sup +/ cells, it is reasonable to suspect mutagenicity based on its DNA-damaging capacity. In the present report, 56 metal compounds were tested by the rec-assay. Compounds showing positive results in the assay such as potassium dichromate (K/sub 2/Cr/sub 2/O/sub 7/), ammonium molybdate ((NH/sub 4/)/sub 6/Mo/sub 7/O/sub 24/) and sodium arsenite (NaAsO/sub 2/) were then examined as to their capacities to induce reversions in E. coli Trp/sup -/ strains possessing different DNA repair pathways. 11 references, 3 tables.

  4. Mutagenic azide metabolite is azidoalanine

    International Nuclear Information System (INIS)

    Owais, W.M.; Rosichan, J.L.; Ronald, R.C.; Kleinhofs, A.; Nilan, R.A.

    1981-01-01

    Sodium axide produces high mutation rates in a number of species. Azide mutagenicity is mediated through a metabolite in barley and bacteria. Many studies showed that azide affects the L-cysteine biosynthesis pathway. Cell-free extracts of Salmonella typhimurium convert azide and O-acetylserine to the mutagenic metabolite. O-acetylserine sulfhydrylase was identified as the enzyme responsible for the metabolite biosynthesis. To confirm the conclusion that the azide metabolite is formed through the β-substitution pathway of L-cysteine, we radioactively labeled the azide metabolite using 14 C-labeled precursors. Moreover, the mutagenic azide metabolite was purified and identified as azidoalanine based on mass spectroscopy and elemental analysis. 26 refs., 3 figs., 1 tab

  5. The impact of locally multiply damaged sites (LMDS) induced by ionizing radiation in mammalian cells

    International Nuclear Information System (INIS)

    Averbeck, D.; Boucher, D.

    2006-01-01

    Monte Carlo calculations have shown that ionising radiations produce a specific type of clustered cell damage called locally multiply damaged sites or LMDS. These lesions consist of closely positioned single-strand breaks, (oxidative) base damage and DNA double-strand breaks (DSB) in between one helical turn of DNA. As specific markers of radiation-induced damage these lesions are likely to condition biological responses and are thus of great interest for radiation protection. Calculations indicate that there should be more LMDS induced by high than by low LET radiation, and they should be absent in un-irradiated cells. Processes like K-shell activation and local Auger electron emission can be expected to add complex DSB or LMDS, producing significant chromosomal damage. In the discussion of the specificity of ionising radiation in comparison to other genotoxic agents, many arguments have been put forward that these lesions should be particularly deleterious for living cells. Complex lesions of that type should represent big obstacles for DNA repair and give rise to high lethality. Moreover, cellular attempts to repair them could accentuate harm, leading to mutations, genetic instability and cancer. In vitro experiments with oligonucleotides containing an artificially introduced set of base damage and SSB in different combinations have shown that depending on the close positioning of the damage on DNA, repair enzymes, and even whole cell extracts, are unable to repair properly and may stimulate mis-repair. Pulsed field gel electrophoresis (PFGE) in conjunction with enzymatic treatments has been used to detect LMDS in mammalian cells after high and low LET radiation. In order to further define the importance of LMDS for radiation induced cellular responses, we studied the induction of LMDS as a function of radiation dose and dose rate in mammalian cells (CHO and MRC5) using 137 Cs gamma-radiation. Using PFGE and specific glycosylases to convert oxidative damage into

  6. The impact of locally multiply damaged sites (LMDS) induced by ionizing radiation in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Averbeck, D.; Boucher, D. [Institut Curie-Section de Recherche, UMR2027 CNRS, LCR-V28 du CEA, Centre Universitaire, 91405 Orsay Cedex (France)

    2006-07-01

    Monte Carlo calculations have shown that ionising radiations produce a specific type of clustered cell damage called locally multiply damaged sites or LMDS. These lesions consist of closely positioned single-strand breaks, (oxidative) base damage and DNA double-strand breaks (DSB) in between one helical turn of DNA. As specific markers of radiation-induced damage these lesions are likely to condition biological responses and are thus of great interest for radiation protection. Calculations indicate that there should be more LMDS induced by high than by low LET radiation, and they should be absent in un-irradiated cells. Processes like K-shell activation and local Auger electron emission can be expected to add complex DSB or LMDS, producing significant chromosomal damage. In the discussion of the specificity of ionising radiation in comparison to other genotoxic agents, many arguments have been put forward that these lesions should be particularly deleterious for living cells. Complex lesions of that type should represent big obstacles for DNA repair and give rise to high lethality. Moreover, cellular attempts to repair them could accentuate harm, leading to mutations, genetic instability and cancer. In vitro experiments with oligonucleotides containing an artificially introduced set of base damage and SSB in different combinations have shown that depending on the close positioning of the damage on DNA, repair enzymes, and even whole cell extracts, are unable to repair properly and may stimulate mis-repair. Pulsed field gel electrophoresis (PFGE) in conjunction with enzymatic treatments has been used to detect LMDS in mammalian cells after high and low LET radiation. In order to further define the importance of LMDS for radiation induced cellular responses, we studied the induction of LMDS as a function of radiation dose and dose rate in mammalian cells (CHO and MRC5) using {sup 137}Cs gamma-radiation. Using PFGE and specific glycosylases to convert oxidative damage

  7. Sources of mutagenic activity in urban fine particles

    International Nuclear Information System (INIS)

    Stevens, R.K.; Lewis, C.W.; Dzubay, T.G.; Cupitt, L.T.; Lewtas, J.

    1990-01-01

    Samples were collected during the winter of 1984-1985 in the cities of Albuquerque, NM and Raleigh NC as part of a US Environmental Protection Agency study to evaluate methods to determine the emission sources contributing to the mutagenic properties of extractable organic matter (EOM) present in fine particles. Data derived from the analysis of the composition of these fine particles served as input to a multi-linear regression (MLR) model used to calculate the relative contribution of wood burning and motor vehicle sources to mutagenic activity observed in the extractable organic matter. At both sites the mutagenic potency of EOM was found to be greater (3-5 times) for mobile sources when compared to wood smoke extractable organics. Carbon-14 measurements which give a direct determination of the amount of EOM that originated from wood burning were in close agreement with the source apportionment results derived from the MLR model

  8. DNA replication after mutagenic treatment in Hordeum vulgare.

    Science.gov (United States)

    Kwasniewska, Jolanta; Kus, Arita; Swoboda, Monika; Braszewska-Zalewska, Agnieszka

    2016-12-01

    The temporal and spatial properties of DNA replication in plants related to DNA damage and mutagenesis is poorly understood. Experiments were carried out to explore the relationships between DNA replication, chromatin structure and DNA damage in nuclei from barley root tips. We quantitavely analysed the topological organisation of replication foci using pulse EdU labelling during the S phase and its relationship with the DNA damage induced by mutagenic treatment with maleic hydrazide (MH), nitroso-N-methyl-urea (MNU) and gamma ray. Treatment with mutagens did not change the characteristic S-phase patterns in the nuclei; however, the frequencies of the S-phase-labelled cells after treatment differed from those observed in the control cells. The analyses of DNA replication in barley nuclei were extended to the micronuclei induced by mutagens. Replication in the chromatin of the micronuclei was rare. The results of simultanous TUNEL reaction to identify cells with DNA strand breaks and the labelling of the S-phase cells with EdU revealed the possibility of DNA replication occurring in damaged nuclei. For the first time, the intensity of EdU fluorescence to study the rate of DNA replication was analysed. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Mutagenicity of cooked foods. Kuumennuskaesiteltyjen elintarvikkeiden mutageenisuus

    Energy Technology Data Exchange (ETDEWEB)

    Tikkanen, L. (Valtion teknillinen tutkimuskeskus, Espoo (Finland). Elintarvikelaboratorio)

    1989-09-01

    In this study the mutagenic activity in different kinds of ordinary Finnish foods was determined using mainly the Ames Salmonella bacterial assay. The purpose of this study was also to acquire the technical capability to study cooked food mutagens and to get basic informavtion about the mutagenic activity of foods under different cooking conditions. The samples tested were different kinds of ready-to-eat foods. Products were industrially heat-processed by frying and roasting, sterilization, smoking, deep-frying, spray-drying and UHT-treatment. According to the results, the majority of the fried and roasted food samples containing meat or fish were clearly or strongly mutagenic. Some of the products processed by sterilization and deep-frying were marginally mutagenic. The effect of the frying temperature on the mutagenicity in the Ames test was studied with minced meat. The mutagenic activity of the fried meat clearly correlated with the frying temperature. There were conspicuous differences in mutagenic activity between different fried and roasted products. Charcoal-grilled fish and the surface layers of the grilled meat and chicken were strongly mutagenic. Meat and fish hamburgers were in most cases only slightly mutagenic. The mutagenic activity was stronger in the surface layers of the products than in the inside. Also reheating by frying increased the mutagenicity of meat patties clearly. Differences in mutagenic activity between equivalent products of different manufacturers were evident in many cases. Variation of the mutagenicity was most conspicuous in the grilled products. This variation indicates that the industrial processing of food has a marked effect on the mutagenic activity of the final product, which thus might be reduced by modifying the process. The solvent extraction method used in this study was more effective than the Blue-Cotton method for the isolation of mutagenic compounds.

  10. Application of mammalian cytogenetics to mutagenicity studies

    International Nuclear Information System (INIS)

    Brewen, J.G.

    1977-01-01

    Studies on induction of chromosome damage in germ cells by triethylene melamine (TEM) included determination of frequencies of chromosomal aberrations observed in human leukocytes after treating different stages of the cell cycle with TEM, frequencies of chromatid aberrations in metaphase I oocytes and the female pronuclear chromosomes following treatment of female mice with TEM, and frequencies of labeled diplotene-diakinesis figures and chromosome abberations at various intervals after treatment of primary spermatocytes with TEM and 3 H-thymidine. Studies on effects of low linear energy transfer radiation on mouse oocytes showed that the frequency of aberrations increased as a function of time and remained constant 8 to 9 days post-exposure. It was concluded that cytogenetic procedures were adequate to evaluate certain mutagenic end points

  11. Spectroscopic study of site selective DNA damage induced by intense soft X-rays

    CERN Document Server

    Fujii, K

    2003-01-01

    To investigate the mechanisms of DNA damage induced by direct photon impact, we observed the near edge X-ray absorption fine structures (NEXAFS) of DNA nucleobases using monochromatic synchrotron soft X-rays around nitrogen and oxygen K-shell excitation regions. Each spectrum obtained has unique structure corresponding to pi* excitation of oxygen or nitrogen 1s electron. These aspects open a way of nucleobase-selective photo-excitation in a DNA molecule using high resolution monochromatized soft X-rays. From the analysis of polarization-dependent intensities of the pi* resonance peak, it is clarified that adenine, guanine an uracil form orientated surface structure. Furthermore from the direct measurement of positive ions desorbed from photon irradiated DNA components, it is revealed that the sugar moiety is a fragile site in a DNA molecule. (author)

  12. Site response, shallow shear-wave velocity, and damage in Los Gatos, California, from the 1989 Loma Prieta earthquake

    Science.gov (United States)

    Hartzell, S.; Carver, D.; Williams, R.A.

    2001-01-01

    Aftershock records of the 1989 Loma Prieta earthquake are used to calculate site response in the frequency band of 0.5-10 Hz at 24 locations in Los Gatos, California, on the edge of the Santa Clara Valley. Two different methods are used: spectral ratios relative to a reference site on rock and a source/site spectral inversion method. These two methods complement each other and give consistent results. Site amplification factors are compared with surficial geology, thickness of alluvium, shallow shear-wave velocity measurements, and ground deformation and structural damage resulting from the Loma Prieta earthquake. Higher values of site amplification are seen on Quaternary alluvium compared with older Miocene and Cretaceous units of Monterey and Franciscan Formation. However, other more detailed correlations with surficial geology are not evident. A complex pattern of alluvial sediment thickness, caused by crosscutting thrust faults, is interpreted as contributing to the variability in site response and the presence of spectral resonance peaks between 2 and 7 Hz at some sites. Within the range of our field measurements, there is a correlation between lower average shear-wave velocity of the top 30 m and 50% higher values of site amplification. An area of residential homes thrown from their foundations correlates with high site response. This damage may also have been aggravated by local ground deformation. Severe damage to commercial buildings in the business district, however, is attributed to poor masonry construction.

  13. Urine mutagenicity of steel workers exposed to coke oven emissions

    Energy Technology Data Exchange (ETDEWEB)

    De Meo, M.P.; Dumenil, G.; Botta, A.H.; Laget, M.; Zabaloueff, V.; Mathias, A.

    1987-03-01

    Urine mutagenicity of 19 individuals was investigated at a steel mill. All the subjects worked on the coal processing unit. Urine samples were collected at the end of a working day. Urine samples of two exposed workers were collected at the end of two periods of rest and two periods of working. Mutagens were extracted on XAD-2 resin and tested by the Salmonella microsomal assay and the SOS spot test. Mutagenic potencies of exposed smokers and exposed non-smokers were 8.62 +/- 6.56 and 1.1 +/- 0.48 revertants/mg creatinine respectively with Salmonella typhimurium strain TA98 + S9. Both values were significantly higher than those of unexposed smokers and non-smokers (5.07 +/- 3.33 and 0.47 +/- 0.72 revertants/mg creatinine respectively). The urinary mutagenic potency of the two exposed individuals increased at the end of periods of working (15.97 +/- 2.57 revertants/mg creatinine) and decreased at the end of periods of rest (12.31 +/- 2.45 revertants/mg creatinine). Urinary mutagens were detected with S. typhimurium strain TA100 + S9 to a lesser extent. No direct-acting mutagens were detected by the SOS spot test. Atmospheric benzo(a)pyrene (BaP) were also measured by h.p.l.c. on the coke battery. BaP concentrations ranged between 0.01 and 0.6 microgram/m3 air at the different working sites. Biological monitoring with short-term tests is discussed.

  14. Assessing Mutagenicity of Methanolic Exteract of Borage Flower (Echium amuenum Using Ames Bioassay

    Directory of Open Access Journals (Sweden)

    Meysam Moosavi

    2014-08-01

    Full Text Available Background: pyrrolizidine alkaloids have been isolated from Echium amuenum. These alkaloids knowing as hepatotoxic, damage the liver. Mutagenicity of pure pyrrolizidine alkaloids has been identified. Thus, the mutagenic effect of the methanolic flower extract was tested using Amest test. Materials and Methods: The long maceration process (for 48 hrs is carried out in order to extract all constitutes. Thin layer chromatography (TLC method was used to evaluate aflatoxin B1 contamination and histidine amino acid presence. Minimum inhibitory concentration (MIC was determined with the dilution method. Salmonella typhimurium strain TA100 was used to determination of mutagenicity. The genotype was confirmed by using histidine requirement, R- factor presence, rfa and uvrB mutations tests. The mutagenicity assay was performed by four extract concentrations (0.25, 0.5, 0.75 and 1mg/ml. Sodium azide (NaN3 and methanol were used as the mutagens (positive control and negative control, respectively in the absence or presence of liver-metabolizing enzymes. Results: The data indicate that Echium amuenum has not significant mutagenic activity against negative control. The presence of liver-metabolizing enzymes did not exhibit a significant change against the properties of extract. Conclusion: It seems that this extensive used plant in traditional medicine, doesn’t contain mutagenic or genotoxic effect in usual doses.

  15. Mutagenic effectiveness and efficiency of EMS, sodium azide and gamma radiation in chickpea (Cicer arietinum L.)

    International Nuclear Information System (INIS)

    Barshile, J.D.; Apparao, B.J.

    2006-01-01

    Mutagenic effectiveness and efficiency of Ethyl Methane Sulphonate (EMS), Sodium Azide (SA) and gamma radiation on two cultivars of chickpea (Cicer arietinum L), Vijay and Vishwas were evaluated by the biological damages caused by them in M 1 generation and on the basis of frequency of chlorophyll mutations produced in the M 2 generation. All mutagenic treatments of EMS, SA and gamma radiation decreased germination, seedling height, plant survival and pollen fertility in both the cultivars. The extent of effect was dose dependent. LD 50 values of mutagen were found to be helpful for planning experimental mutagenesis in chickpea. Frequency of chlorophyll mutations in M 2 generation was less in Vijay as compared to Vishwas. Mutagenic effectiveness is inversely proportional to the increasing concentrations/doses of mutagens in both the cultivars, except for gamma radiation treatments in the cultivar Vishwas. All three mutagens (except EMS in the Vijay and gamma radiation in the cultivar Vishwas) exhibited gradual decrease in mutagenic efficiency, with an increase in their concentration/dose. (author)

  16. Mutagenicity tests on irradiated food

    International Nuclear Information System (INIS)

    Johnston-Arthur, T.

    1979-01-01

    The mutagenicity of ''standard'' food pellets from three different suppliers was tested after radappertization and after sterilization with steam, respectively. The histidine-deficient mutants G-46 and TA-1530 of salmonella typhimurium were used as indicators in a hostmediated assay. The mutant TA-1530 showed a highly sighificant increase of the back-mutation frequency after feeding with pellets irradiated with 3 Mrad gamma radiation. There were, however, large quantitative differences between the products of different suppliers. (G.G.)

  17. Multiple-site damage crack growth behaviour in Fibre Metal Laminate structures

    NARCIS (Netherlands)

    Wang, W.

    2017-01-01

    Fibre metal laminates (FMLs)were developed and refined for their superior crack growth resistance and critical damage size that complimented the damage tolerance design philosophy utilized in the aerospace sector. Robust damage tolerance tools have been developed for FMLs. However, they tend to

  18. Differences in mutagenic and recombinational DNA repair in enterobacteria

    International Nuclear Information System (INIS)

    Sedgwick, S.G.; Goodwin, P.A.

    1985-01-01

    The incidence of recombinational DNA repair and inducible mutagenic DNA repair has been examined in Escherichia coli and 11 related species of enterobacteria. Recombinational repair was found to be a common feature of the DNA repair repertoire of at least 6 genera of enterobacteria. This conclusion is based on observations of (i) damage-induced synthesis of RecA-like proteins, (ii) nucleotide hybridization between E. coli recA sequences and some chromosomal DNAs, and (iii) recA-negative complementation by plasmids showing SOS-inducible expression of truncated E. coli recA genes. The mechanism of DNA damage-induced gene expression is therefore sufficiently conserved to allow non-E. coli regulatory elements to govern expression of these cloned truncated E. coli recA genes. In contrast, the process of mutagenic repair, which uses umuC+ umuD+ gene products in E. coli, appeared less widespread. Little ultraviolet light-induced mutagenesis to rifampicin resistance was detected outside the genus Escherichia, and even within the genus induced mutagenesis was detected in only 3 out of 6 species. Nucleotide hybridization showed that sequences like the E. coli umuCD+ gene are not found in these poorly mutable organisms. Evolutionary questions raised by the sporadic incidence of inducible mutagenic repair are discussed

  19. Tumor Suppressor Genes within Common Fragile Sites Are Active Players in the DNA Damage Response.

    Directory of Open Access Journals (Sweden)

    Idit Hazan

    2016-12-01

    Full Text Available The role of common fragile sites (CFSs in cancer remains controversial. Two main views dominate the discussion: one suggests that CFS loci are hotspots of genomic instability leading to inactivation of genes encoded within them, while the other view proposes that CFSs are functional units and that loss of the encoded genes confers selective pressure, leading to cancer development. The latter view is supported by emerging evidence showing that expression of a given CFS is associated with genome integrity and that inactivation of CFS-resident tumor suppressor genes leads to dysregulation of the DNA damage response (DDR and increased genomic instability. These two viewpoints of CFS function are not mutually exclusive but rather coexist; when breaks at CFSs are not repaired accurately, this can lead to deletions by which cells acquire growth advantage because of loss of tumor suppressor activities. Here, we review recent advances linking some CFS gene products with the DDR, genomic instability, and carcinogenesis and discuss how their inactivation might represent a selective advantage for cancer cells.

  20. Mutagenic effect of tritated water on spores of Bacillus subtilis

    International Nuclear Information System (INIS)

    Tanooka, H.; Munakata, N.

    1978-01-01

    The mutagenic effect of tritiated water was observed with spores of Bacillus subtilis polA strain suspended in 50 mCi/ml of tritiated water for various intervals. Dose rate given by tritium beta particles to spore core was estimated to be 400 rad/hr from some assumptions and E. coli data computed by Bockrath et al. and Sands et al. The initial mutation rate was 4.2 x 10 -9 mutants/rad, as compared with 2.4 x 10 -9 mutants/rad for 60 Co γ rays and 3.3 x 10 -9 mutants/rad for 30-kVp x rays. The mutagenic effect of tritiated water on spores is most likely due to beta particle ionizing radiation damage

  1. Radiation-induced mutagenicity and lethality in Salmonella typhimurium

    International Nuclear Information System (INIS)

    Isildar, M.; Bakale, G.

    1983-01-01

    The mutagenic and lethal effects of ionizing radiation on histidine-deficient auxotrophs of Salmonella typhimurium were studied to improve the understanding of radiation damage to DNA. The auxotrophs were divided into two groups - one which is sensitive to base-pair substitutions and another sensitive to frameshifts. These groups were composed of parent-daughter pairs in which the chemical mutagenicity enhancing plasmid, pKM101, is absent in the parent strain and present in the daughter. Co-60 #betta#-radiation and 250 kV x-rays were used to irradiate the bacteria. Irradiation of the frameshift - sensitive strains which carry the pKm101 plasmid doubled the absolute number of induced revertants whereas irradiation of the base-pair substitution sensitive strain which also carries the pKm101 plasmid produced nearly no change in the number of induced revertants. A nearly negligible effect on the mutation rate was observed for all parent strains

  2. Modeling the yield of double-strand breaks due to formation of multiply damaged sites in irradiated plasmid DNA

    International Nuclear Information System (INIS)

    Xapsos, M.A.; Pogozelski, W.K.

    1996-01-01

    Although double-strand breaks have long been recognized as an important type of DNa lesion, it is well established that this broad class of damage does not correlate well with indicators of the effectiveness of radiation as the cellular level. Assays of double-strand breaks do not distinguish the degree of complexity or clustering of singly damaged sites produced in a single energy deposition event, which is currently hypothesized to be key to understanding cellular end points. As a step toward this understanding, double-strand breaks that are formed proportionally to dose in plasmid DNA are analyzed from the mechanistic aspect to evaluate the yield that arises from multiply damaged sites as hypothesized by Ward (Prog. Nucleic Acid Res. Mol. Biol. 35, 95-125, 1988) and Goodhead (Int. J. Radiat. Biol. 65, 7-17, 1994) as opposed to the yield that arises form single hydroxyl radicals as hypothesized by Siddiqi and Bothe (Radiat. Res. 112, 449-463, 1987). For low-LET radiation such as γ rays, the importance of multiply damaged sites is shown to increase with the solution's hydroxyl radical scavenging capacity. For moderately high-LET radiation such as 100 keV/μm helium ions, a much different behavior is observed. In this case, a large fraction of double-strand breaks are formed as a result of multiply damaged sties over a broad range of scavenging conditions. Results also indicate that the RBE for common cellular end points correlates more closely with the RBE for common cellular end points correlates more closely with the RBE for multiply damaged sites than with the RBE for total double-strand breaks over a range of LET up to at least 100 keV/μm. 22 refs., 3 figs., 2 tabs

  3. Repair of oxidative DNA base damage in the host genome influences the HIV integration site sequence preference.

    Directory of Open Access Journals (Sweden)

    Geoffrey R Bennett

    Full Text Available Host base excision repair (BER proteins that repair oxidative damage enhance HIV infection. These proteins include the oxidative DNA damage glycosylases 8-oxo-guanine DNA glycosylase (OGG1 and mutY homolog (MYH as well as DNA polymerase beta (Polβ. While deletion of oxidative BER genes leads to decreased HIV infection and integration efficiency, the mechanism remains unknown. One hypothesis is that BER proteins repair the DNA gapped integration intermediate. An alternative hypothesis considers that the most common oxidative DNA base damages occur on guanines. The subtle consensus sequence preference at HIV integration sites includes multiple G:C base pairs surrounding the points of joining. These observations suggest a role for oxidative BER during integration targeting at the nucleotide level. We examined the hypothesis that BER repairs a gapped integration intermediate by measuring HIV infection efficiency in Polβ null cell lines complemented with active site point mutants of Polβ. A DNA synthesis defective mutant, but not a 5'dRP lyase mutant, rescued HIV infection efficiency to wild type levels; this suggested Polβ DNA synthesis activity is not necessary while 5'dRP lyase activity is required for efficient HIV infection. An alternate hypothesis that BER events in the host genome influence HIV integration site selection was examined by sequencing integration sites in OGG1 and MYH null cells. In the absence of these 8-oxo-guanine specific glycosylases the chromatin elements of HIV integration site selection remain the same as in wild type cells. However, the HIV integration site sequence preference at G:C base pairs is altered at several positions in OGG1 and MYH null cells. Inefficient HIV infection in the absence of oxidative BER proteins does not appear related to repair of the gapped integration intermediate; instead oxidative damage repair may participate in HIV integration site preference at the sequence level.

  4. Structural Basis of Mec1-Ddc2-RPA Assembly and Activation on Single-Stranded DNA at Sites of Damage.

    Science.gov (United States)

    Deshpande, Ishan; Seeber, Andrew; Shimada, Kenji; Keusch, Jeremy J; Gut, Heinz; Gasser, Susan M

    2017-10-19

    Mec1-Ddc2 (ATR-ATRIP) is a key DNA-damage-sensing kinase that is recruited through the single-stranded (ss) DNA-binding replication protein A (RPA) to initiate the DNA damage checkpoint response. Activation of ATR-ATRIP in the absence of DNA damage is lethal. Therefore, it is important that damage-specific recruitment precedes kinase activation, which is achieved at least in part by Mec1-Ddc2 homodimerization. Here, we report a structural, biochemical, and functional characterization of the yeast Mec1-Ddc2-RPA assembly. High-resolution co-crystal structures of Ddc2-Rfa1 and Ddc2-Rfa1-t11 (K45E mutant) N termini and of the Ddc2 coiled-coil domain (CCD) provide insight into Mec1-Ddc2 homodimerization and damage-site targeting. Based on our structural and functional findings, we present a Mec1-Ddc2-RPA-ssDNA composite structural model. By way of validation, we show that RPA-dependent recruitment of Mec1-Ddc2 is crucial for maintaining its homodimeric state at ssDNA and that Ddc2's recruitment domain and CCD are important for Mec1-dependent survival of UV-light-induced DNA damage. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Decision-making system for registration and prioritisation of potentially polluted sites adaptable for management of war damage risks

    International Nuclear Information System (INIS)

    Lanczos, T.; Pedersen, K. E.

    2002-01-01

    We would like to present a decision-support system developed for identification and storing data concerning with potentially polluted sites and their prioritising. This system could also be adapted for reviewing and evaluation of the war damages. The operation of the system comprises of three procedures: data collection, data handling and the prioritisation of the sites. The relevant data could be collected from different sources, represented mainly by administrative institutions, by sending questionnaires to site owners/operators and by site visits. The collected data should be handled by appropriate database. For this purpose the Contaminated Land Module of the GeoEnviron database application was developed. This application is also designed for providing the preliminary risk assessment scores, which results are used for the site prioritisation. As an example implementation of this system, we shortly present our experiences from testing the system in Slovakia

  6. New approaches to assessing the effects of mutagenic agents on the integrity of the human genome

    International Nuclear Information System (INIS)

    Elespuru, R.K.; Sankaranarayanan, K.

    2007-01-01

    Heritable genetic alterations, although individually rare, have a substantial collective health impact. Approximately 20% of these are new mutations of unknown cause. Assessment of the effect of exposures to DNA damaging agents, i.e. mutagenic chemicals and radiations, on the integrity of the human genome and on the occurrence of genetic disease remains a daunting challenge. Recent insights may explain why previous examination of human exposures to ionizing radiation, as in Hiroshima and Nagasaki, failed to reveal heritable genetic effects. New opportunities to assess the heritable genetic damaging effects of environmental mutagens are afforded by: (1) integration of knowledge on the molecular nature of genetic disorders and the molecular effects of mutagens; (2) the development of more practical assays for germline mutagenesis; (3) the likely use of population-based genetic screening in personalized medicine

  7. Mycobacterial nonhomologous end joining mediates mutagenic repair of chromosomal double-strand DNA breaks.

    Science.gov (United States)

    Stephanou, Nicolas C; Gao, Feng; Bongiorno, Paola; Ehrt, Sabine; Schnappinger, Dirk; Shuman, Stewart; Glickman, Michael S

    2007-07-01

    Bacterial nonhomologous end joining (NHEJ) is a recently described DNA repair pathway best characterized in mycobacteria. Bacterial NHEJ proteins LigD and Ku have been analyzed biochemically, and their roles in linear plasmid repair in vivo have been verified genetically; yet the contributions of NHEJ to repair of chromosomal DNA damage are unknown. Here we use an extensive set of NHEJ- and homologous recombination (HR)-deficient Mycobacterium smegmatis strains to probe the importance of HR and NHEJ in repairing diverse types of chromosomal DNA damage. An M. smegmatis Delta recA Delta ku double mutant has no apparent growth defect in vitro. Loss of the NHEJ components Ku and LigD had no effect on sensitivity to UV radiation, methyl methanesulfonate, or quinolone antibiotics. NHEJ deficiency had no effect on sensitivity to ionizing radiation in logarithmic- or early-stationary-phase cells but was required for ionizing radiation resistance in late stationary phase in 7H9 but not LB medium. In addition, NHEJ components were required for repair of I-SceI mediated chromosomal double-strand breaks (DSBs), and in the absence of HR, the NHEJ pathway rapidly mutates the chromosomal break site. The molecular outcomes of NHEJ-mediated chromosomal DSB repair involve predominantly single-nucleotide insertions at the break site, similar to previous findings using plasmid substrates. These findings demonstrate that prokaryotic NHEJ is specifically required for DSB repair in late stationary phase and can mediate mutagenic repair of homing endonuclease-generated chromosomal DSBs.

  8. Carcinogenicity and mutagenicity of chromium.

    Science.gov (United States)

    Léonard, A; Lauwerys, R R

    1980-11-01

    Occupational exposure represents the main source of human contamination by chromium. For non-occupationally exposed people the major environmental exposure to chromium occurs as a consequence of its presence in food. Chromium must be considered as an essential element. Its deficiency impairs glucose metabolism. Trivalent chromium salts are poorly absorbed through the gastro-intestinal and respiratory tracts because they do not cross membranes easily. Hexavalent chromium can be absorbed by the oral and pulmonary routes and probably also through the skin. After its absorption, hexavalent chromium is rapidly reduced to the trivalent form which is probably the only form to be found in biological material. Epidemiological studies have shown that some chromium salts (mainly the slightly soluble hexavalent salts) are carcinogens. Lung cancers have, indeed, often been reported among workers in chromate-producing industry and, to a lesser extent, in workers from the chrome-pigment industry. The first attempts to produce cancers in experimental animals by inhalation or parenteral introduction gave negative or equivocal results but, from 1960, positive results have been obtained with various chromium compounds. As for the carcinogenic activity, the mutagenicity of chromium has mainly been found with hexavalent salts. In the majority of assay systems used, trivalent chromium appears inactive. It can be considered as evident, however, that the ultimate mutagen which binds to the genetic material is the trivalent form produced intracellularly from hexavalent chromium, the apparent lack of activity of the trivalent form being due to its poor cellular uptake.

  9. Mutagenicity of vinyl chloride after metabolic activation

    Energy Technology Data Exchange (ETDEWEB)

    Rannug, U; Johansson, A; Ramel, C; Wachtmeister, C A

    1974-01-01

    Vinyl chloride has recently been shown to cause a malignant liver tumor disease in man after occupational exposure in PVC plants. This actualizes the problem of whether such hazards could be avoided or at least diminished in the future by a screening for mutagenicity of chemicals used in industries. The basis for such a screening procedure is the close correlation between carcinogenic and mutagenic effects of chemicals. Experiments with Salmonella bacteria showed that the carcinogenic hazard of vinyl chloride could have been traced by means of mutagenicity tests. The data indicate that vinyl chloride is not mutagenic per se but becomes mutagenic after a metabolic activation in the liver. 24 references, 1 figure, 4 tables.

  10. Vascular nanomedicine: Site specific delivery of elastin stabilizing therapeutics to damaged arteries

    Science.gov (United States)

    Sinha, Aditi

    improved resistance to elastolytic digestion. We further show that the same polyphenols interact with monomeric tropoelastin released by the vascular cells and dramatically increasing their self-assembly in-vitro. In addition, we demonstrate the elastogenic ability of these polyphenols in aiding the crosslinking of tropoelastin released by aneurysmal cells converting it into mature elastin. Finally, we developed a nanoparticle system functionalized with elastin antibody on the surface that, upon systemic delivery, can recognize and bind to sites of damaged elastin in the aorta. We are able to show that this nanoparticle system works in representative animal models for MAC and AAA. These nanoparticles demonstrated spatial and functional specificity for degraded elastin. In conclusion, our work is focused on understanding the role of elastin degradation in vascular calcification and aortic aneurysms. We tested approaches to halt elastin degradation and to regenerate elastin in arteries so that homeostasis can be achieved.

  11. Chromosome damage in Chinese hamster cells produced by 125I-UdR at the site of its incorporation

    International Nuclear Information System (INIS)

    Hughes, W.L.; Weinblatt, A.C.; Prensky, W.

    1978-01-01

    Metaphase chromosomal aberrations were produced by 125 I-labeled iododeoxyuridine ( 125 I-UdR) incorporated into Chinese hamster Don cells at the end of the S-period of the cell cycle. Chromosome damage and the number of autoradiographic silver grains were recorded for whole cells, for chromosome pairs 4 and 5 and for the X and the Y chromosomes. The X and the Y chromosomes, which label late in S, were at least twice as heavily labeled as chromosome pairs 4 and 5 - two readily recognizable autosomes of similar size. The incidence of chromosome damage was at least six times that which would have been expected from equivalent doses of X-rays and the incidence of damage was directly related to the number of silver grains over each chromosome. It is estimated that it takes four to ten disintegrations to produce a visible chromosome aberration. The finding that chromosome damage is localized at the site of the 125 I decay is most readily explained by the high flux of low energy Auger electrons occurring at the site of the decay of the incorporated 125 I atom. (Auth.)

  12. Similar distributions of repaired sites in chromatin of normal and xeroderma pigmentosum variant cells damaged by ultraviolet light

    International Nuclear Information System (INIS)

    Cleaver, J.E.

    1979-01-01

    Excision repair of damage from ultraviolet light in both normal and xeroderma pigmentosum variant fibroblasts at early times after irradiation occurred preferentially in regions of DNA accessible to micrococcal nuclease digestion. These regions are predominantly the linker regions between nucleosomes in chromatin. The alterations reported at polymerization and ligation steps of excision repair in the variant are therefore not associated with changes in the relative distributions of repair sites in linker and core particle regions of DNA. (Auth.)

  13. New method for estimating clustering of DNA lesions induced by physical/chemical mutagens using fluorescence anisotropy.

    Science.gov (United States)

    Akamatsu, Ken; Shikazono, Naoya; Saito, Takeshi

    2017-11-01

    We have developed a new method for estimating the localization of DNA damage such as apurinic/apyrimidinic sites (APs) on DNA using fluorescence anisotropy. This method is aimed at characterizing clustered DNA damage produced by DNA-damaging agents such as ionizing radiation and genotoxic chemicals. A fluorescent probe with an aminooxy group (AlexaFluor488) was used to label APs. We prepared a pUC19 plasmid with APs by heating under acidic conditions as a model for damaged DNA, and subsequently labeled the APs. We found that the observed fluorescence anisotropy (r obs ) decreases as averaged AP density (λ AP : number of APs per base pair) increases due to homo-FRET, and that the APs were randomly distributed. We applied this method to three DNA-damaging agents, 60 Co γ-rays, methyl methanesulfonate (MMS), and neocarzinostatin (NCS). We found that r obs -λ AP relationships differed significantly between MMS and NCS. At low AP density (λ AP  < 0.001), the APs induced by MMS seemed to not be closely distributed, whereas those induced by NCS were remarkably clustered. In contrast, the AP clustering induced by 60 Co γ-rays was similar to, but potentially more likely to occur than, random distribution. This simple method can be used to estimate mutagenicity of ionizing radiation and genotoxic chemicals. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Molecular basis of the mutagenic and lethal effects of ultraviolet irradiation

    International Nuclear Information System (INIS)

    Grossman, L.

    1982-01-01

    Using bacteria as a model, the molecular basis of the mutagenic and lethal effects of uv radiation is being studied. Attention is focused on the mechanism of action of uv-1 specific endonucleases in the repair of damaged DNA. The isolation and identification of similar enzymes in human cells are being conducted concurrently

  15. Fukushima Daiichi nuclear acccident. Damaged facilities of the site - Situation as on March 2018

    International Nuclear Information System (INIS)

    2018-03-01

    After a recall of the events that led to the Fukushima Daiichi accident, this note presents the situation in March 2018 of the actions of control of the damaged facilities and of their effluents. The last part presents the three steps of the facility control recovery plan retained by TEPCO

  16. Mutagenicity and genotoxicity of coal fly ash water leachate.

    Science.gov (United States)

    Chakraborty, Rajarshi; Mukherjee, Anita

    2009-03-01

    Fly ash is a by-product of coal-fired electricity generation plants. The prevalent practice of disposal is as slurry of ash and water to storage or ash ponds located near power stations. This has lain to waste thousands of hectares of land all over the world. Since leaching is often the cause of off-site contamination and pathway of introduction into the human environment, a study on the genotoxic effects of fly ash leachate is essential. Leachate prepared from the fly ash sample was analyzed for metal content, and tested for mutagenicity and genotoxicity. Analyses of metals show predominance of the metals-sodium, silicon, potassium, calcium, magnesium, iron, manganese, zinc, and sulphate. The Ames Salmonella mutagenicity assay, a short-term bacterial reverse mutation assay, was conducted on two-tester strains of Salmonella typhimurium strains TA97a and TA102. For genotoxicity, the alkaline version of comet assay on fly ash leachate was carried in vitro on human blood cells and in vivo on Nicotiana plants. The leachate was directly mutagenic and induced significant (Ppercentage (%), tail length (mum), and olive tail moment (arbitrary units). Our results indicate that leachate from fly ash dumpsites has the genotoxic potential and may lead to adverse effects on vegetation and on the health of exposed human populations.

  17. DNA repair in mutagen-injured higher plants

    International Nuclear Information System (INIS)

    Veleminsky, J.; Gichner, T.

    1978-01-01

    Data are summarized proving the occurrence of photoreactivation of UV-induced pyrimidine dimers in cells of Nicotiana tabucum, Gingko and carrot, the excision of dimers in cells of Nicotiana tabacum, Gingko and carrot, the excision of dimers in protoplasts of carrot and in embryos of Lathyrus sativus, and the repair of DNA single-strand breaks induced in carrot protoplasts and barley embryonic cells by ionizing radiation. In irradiated barley embryos the unscheduled DNA synthesis and higher accessibility of induced primers to DNA polymerase I of E. coli were observed preferentially in G 1 cells with diffused chromatin. These reactions were inhibited by caffeine and EDTA. Unscheduled DNA synthesis was also observed in synchronized irradiated root cuttings of Vicia faba and in barley embryos treated with 4-nitroquinoline oxide, the latter being inhibited by caffeine and hydroxyurea. Repair synthesis was also established in barley embryos treated with mutagenic N-methyl-N-nitrosourea under conditions that postponed the onset of germination after the treatment. The same conditions enhanced the repair of DNA single-strand breaks induced by this mutagen and several other monofunctional alkylating compounds. From tissues of barley and of Phaseolus multiflorus, endonucleases for apurinic sites were isolated and characterized. Some of them are located in chromatin, others in chloroplasts. The relation between DNA repair and genetic effects of mutagens in higher plants is also discussed. (Auth.)

  18. Codon cassette mutagenesis: a general method to insert or replace individual codons by using universal mutagenic cassettes.

    Science.gov (United States)

    Kegler-Ebo, D M; Docktor, C M; DiMaio, D

    1994-05-11

    We describe codon cassette mutagenesis, a simple method of mutagenesis that uses universal mutagenic cassettes to deposit single codons at specific sites in double-stranded DNA. A target molecule is first constructed that contains a blunt, double-strand break at the site targeted for mutagenesis. A double-stranded mutagenic codon cassette is then inserted at the target site. Each mutagenic codon cassette contains a three base pair direct terminal repeat and two head-to-head recognition sequences for the restriction endonuclease Sapl, an enzyme that cleaves outside of its recognition sequence. The intermediate molecule containing the mutagenic cassette is then digested with Sapl, thereby removing most of the mutagenic cassette, leaving only a three base cohesive overhang that is ligated to generate the final insertion or substitution mutation. A general method for constructing blunt-end target molecules suitable for this approach is also described. Because the mutagenic cassette is excised during this procedure and alters the target only by introducing the desired mutation, the same cassette can be used to introduce a particular codon at all target sites. Each cassette can deposit two different codons, depending on the orientation in which it is inserted into the target molecule. Therefore, a series of eleven cassettes is sufficient to insert all possible amino acids at any constructed target site. Thus codon cassettes are 'off-the-shelf' reagents, and this methodology should be a particularly useful and inexpensive approach for subjecting multiple different positions in a protein sequence to saturation mutagenesis.

  19. The formation of double-strand breaks at multiply damaged sites is driven by the kinetics of excision/incision at base damage in eukaryotic cells

    International Nuclear Information System (INIS)

    Kozmin, S.G.; Sedletska, Y.; Reynaud-Angelin, A.; Sage, E.; Kozmin, S.G.; Sedletska, Y.; Reynaud-Angelin, A.; Sage, E.; Gasparutto, D.

    2009-01-01

    It has been stipulated that repair of clustered DNA lesions may be compromised, possibly leading to the formation of double-strand breaks (DSB) and, thus, to deleterious events. Using a variety of model multiply damaged sites (MDS), we investigated parameters that govern the formation of DSB during the processing of MDS. Duplexes carrying MDS were inserted into replicative or integrative vectors, and used to transform yeast Saccharomyces cerevisiae. Formation of DSB was assessed by a relevant plasmid survival assay. Kinetics of excision/incision and DSB formation at MDS was explored using yeast cell extracts. We show that MDS composed of two uracils or abasic sites, were rapidly incised and readily converted into DSB in yeast cells. In marked contrast, none of the MDS carrying opposed oG and hU separated by 38 bp gave rise to DSB, despite the fact that some of them contained preexisting single-strand break (a 1-nt gap). Interestingly, the absence of DSB formation in this case correlated with slow excision/incision rates of lesions. We propose that the kinetics of the initial repair steps at MDS is a major parameter that direct towards the conversion of MDS into DSB. Data provides clues to the biological consequences of MDS in eukaryotic cells. (authors)

  20. MSD in fuselage lap joints: Requirements for inspection intervals for typical fuselage lap joint panels with Multiple Site Damage

    Science.gov (United States)

    Wit, G. P.

    1992-07-01

    Inspection of failed aircraft structures and fractography on fatigue specimens showed that after a high number of flights, cracks can appear simultaneously in riveted lap joints. When these crack tips approach each other, a mutual interaction causes an unexpected fast crack growth and new coalescence of cracks. The term Multiple Site Damage (MSD) is used when the mutual interaction of two or more damages is noticeable. A model to predict the fatigue life of a riveted lap joint and the minimum necessary inspection interval for safe aircraft operation is presented. The program was developed to simulate the fatigue process and aircraft inspection. Input for this analysis are scatter data for initiation, the stress distribution between frames and the geometry of the structure. Methods that can be used to avoid accidents due to MSD are reviewed. A test program to support the analysis is described.

  1. Multi-method Near-surface Geophysical Surveys for Site Response and Earthquake Damage Assessments at School Sites in Washington, USA

    Science.gov (United States)

    Cakir, R.; Walsh, T. J.; Norman, D. K.

    2017-12-01

    We, Washington Geological Survey (WGS), have been performing multi-method near surface geophysical surveys to help assess potential earthquake damage at public schools in Washington. We have been conducting active and passive seismic surveys, and estimating Shear-wave velocity (Vs) profiles, then determining the NEHRP soil classifications based on Vs30m values at school sites in Washington. The survey methods we have used: 1D and 2D MASW and MAM, P- and S-wave refraction, horizontal-to-vertical spectral ratio (H/V), and 2ST-SPAC to measure Vs and Vp at shallow (0-70m) and greater depths at the sites. We have also run Ground Penetrating Radar (GPR) surveys at the sites to check possible horizontal subsurface variations along and between the seismic survey lines and the actual locations of the school buildings. The seismic survey results were then used to calculate Vs30m for determining the NEHRP soil classifications at school sites, thus soil amplification effects on the ground motions. Resulting shear-wave velocity profiles generated from these studies can also be used for site response and liquefaction potential studies, as well as for improvement efforts of the national Vs30m database, essential information for ShakeMap and ground motion modeling efforts in Washington and Pacific Northwest. To estimate casualties, nonstructural, and structural losses caused by the potential earthquakes in the region, we used these seismic site characterization results associated with structural engineering evaluations based on ASCE41 or FEMA 154 (Rapid Visual Screening) as inputs in FEMA Hazus-Advanced Engineering Building Module (AEBM) analysis. Compelling example surveys will be presented for the school sites in western and eastern Washington.

  2. Mutagenicity studies with the mouse spot test

    Energy Technology Data Exchange (ETDEWEB)

    Gocke, E.; Wild, D.; Eckhardt, K.; King, M.T.

    1983-04-01

    The mammalian spot test, which detects somatic gene mutations in mouse embryos, was investigated with selected chemicals to (a) further validate this test system ethylnitrosourea, ethyl methanesulfonate, 2-acetylaminofluorene and colchicine (ENU, EMS, 2AAF), and (b) evaluate the mutagenic potential, in a whole-mammal system, of environmental compounds that had been previously recognized as mutagens in other mammalian or submammalian test systems (1,2-dichloroethane, hydroquinone, nitrofurantoin, o-phenylenediamine, fried sausage extract). Of these substances, ENU, EMS and 2AAF were significantly mutagenic, 1,2-dichloroethane was probably weakly mutagenic. The ENU data were used to estimate the number of pigment precursor cells present at the time of treatment (day 9.25). We also describe in this report the use of a fluorescence microscope for classification of hairs from spots on the coat of C57BL/6JHan X T hybrids.

  3. BRCA1-associated exclusion of 53BP1 from DNA damage sites underlies temporal control of DNA repair

    Science.gov (United States)

    Chapman, J. Ross; Sossick, Alex J.; Boulton, Simon J.; Jackson, Stephen P.

    2012-01-01

    Summary Following irradiation, numerous DNA-damage-responsive proteins rapidly redistribute into microscopically visible subnuclear aggregates, termed ionising-radiation-induced foci (IRIF). How the enrichment of proteins on damaged chromatin actually relates to DNA repair remains unclear. Here, we use super-resolution microscopy to examine the spatial distribution of BRCA1 and 53BP1 proteins within single IRIF at subdiffraction-limit resolution, yielding an unprecedented increase in detail that was not previously apparent by conventional microscopy. Consistent with a role for 53BP1 in promoting DNA double-strand break repair by non-homologous end joining, 53BP1 enrichment in IRIF is most prominent in the G0/G1 cell cycle phases, where it is enriched in dense globular structures. By contrast, as cells transition through S phase, the recruitment of BRCA1 into the core of IRIF is associated with an exclusion of 53BP1 to the focal periphery, leading to an overall reduction of 53BP1 occupancy at DNA damage sites. Our data suggest that the BRCA1-associated IRIF core corresponds to chromatin regions associated with repair by homologous recombination, and the enrichment of BRCA1 in IRIF represents a temporal switch in the DNA repair program. We propose that BRCA1 antagonises 53BP1-dependent DNA repair in S phase by inhibiting its interaction with chromatin proximal to damage sites. Furthermore, the genomic instability exhibited by BRCA1-deficient cells might result from a failure to efficiently exclude 53BP1 from such regions during S phase. PMID:22553214

  4. Mutagenic activities of biochars from pyrolysis.

    Science.gov (United States)

    Piterina, Anna V; Chipman, J Kevin; Pembroke, J Tony; Hayes, Michael H B

    2017-08-15

    Biochar production, from pyrolysis of lignocellulosic feedstocks, agricultural residues, and animal and poultry manures are emerging globally as novel industrial and commercial products. It is important to develop and to validate a series of suitable protocols for the ecological monitoring of the qualities and properties of biochars. The highly sensitive Salmonella mutagenicity assays (the Ames test) are used widely by the toxicology community and, via the rat liver extract (S9), can reflect the potential for mammalian metabolic activation. We examined the Ames test for analyses of the mutagenic activities of dimethylsulphoxide (DMSO) extracts of biochars using two bacterial models (S. typhimurium strains TA98 and TA100) in the presence and in the absence of the metabolic activation with the S9-mix. Tester strain TA98 was most sensitive in detecting mutagenic biochar products, and the contribution of S9 was established. Temperature and times of pyrolysis are important. Biochar pyrolysed at 400°C for 10min, from a lignocellulose precursor was mutagenic, but not when formed at 800°C for 60min, or at 600°C for 30min. Biochars from poultry litter, and manures of calves fed on grass had low mutagenicities. Biochar from pig manure had high mutagenicity; biochars from manures of cows fed on a grass plus cereals, those of calves fed on mother's milk, and biochars from solid industrial waste had intermediate mutagenicities. The methods outlined can indicate the need for further studies for screening and detection of the mutagenic residuals in a variety of biochar products. Copyright © 2017. Published by Elsevier B.V.

  5. Hygiene assessment of irradiated potato mutagenic activity

    International Nuclear Information System (INIS)

    Uralova, M.; Grunt, J.; Patzeltova, N.

    1977-01-01

    Albino rat males were fed on gamma-irradiated potatoes for one month and mated with two intact female rats each. The dominant lethal mutation method was then used for the study of possible mutagenic activity of the irradiated potatoes. No statistically significant differences were observed and no mutagenic activity was found. Thus, the test showed that potatoes irradiated with a dose of 10 krad of gamma radiation does not present genetic hazards for albino rats. (L.O.)

  6. Mutagenic and carcinogenic properties of drinking water

    International Nuclear Information System (INIS)

    Kool, H.J.; van Kreijl, C.F.; Hrubec, J.

    1985-01-01

    In this chapter results of oxidation treatments with chlorine, ozone, chlorine dioxide, and ultraviolet (UV), with respect to their effects on activity (Ames test) in drinking water supplies are reviewed. In addition, the authors present the preliminary results of a pilot plant study on the effects of chlorine and chlorine dioxide on mutagenicity. Furthermore, results of several carcinogenicity studies performed with organic drinking water concentrates are discussed in relation to the results of a Dutch carcinogenicity study with mutagenic drinking water concentrates

  7. Kaempferol, a mutagenic flavonol from Helichrysum simillimum.

    Science.gov (United States)

    Elgorashi, Ee; van Heerden, Fr; van Staden, J

    2008-11-01

    Helichrysum simillimum is native to South Africa. It is used for the treatment of coughs, colds, fever, infections, headache, and menstrual pain. Extracts of this species showed mutagenic effects in the Salmonella/microsome assay. The aim of this study was to isolate and determine the mutagenic constituents of H. simillimum. Bioassay-guided fractionation of 90% aqueous methanol extracts, using Salmonella typhimurium TA98, led to the isolation of the flavonol kaempferol.

  8. Modulation of mutagen-induced biological effects by inhibitors of DNA repair

    International Nuclear Information System (INIS)

    Natarajan, A.T.; Mullenders, L.F.H.; Zwanenburg, T.S.B.

    1986-01-01

    When lesions are induced in the DNA by mutagenic agents, they are subjected to cellular repair. Unrepaired and misrepaired lesions lead to biological effects, such as cell killing, point mutations and chromosomal alterations (aberrations and sister chromatid exchanges - SCEs). It is very difficult to directly correlate any particular type of lesion to a specific biological effect. However, in specific cases, this has been done. For example, short wave UV induced biological effects (cell killing, chromosomal alterations) result predominantly from induced cyclobutane dimers and by photoreactivation experiments, one can demonstrate that with the removal of dimers all types biological effects are diminished. In cases where many types of lesions are considered responsible for the observed biological effects other strategies have been employed to identify the possible lesion. The frequencies of induced chromosomal alterations and point mutations increase with the dose of the mutagen employed and an inhibition of DNA repair following treatment with the mutagen. Prevention of the cells from dividing following mutagen treatment allows them to repair premutational damage, thus reducing the biological effects induced. By comprehensive studies involving quantification of primary DNA lesions, their repair and biological effects will enable us to understand to some extent the complex processes involved in the manifestation of specific biological effects that follow the treatment of cells with mutagenic carcinogens

  9. Mutagenic and genotoxic activity of particulate matter MP2,5, in Pamplona, North Santander, Colombia

    Directory of Open Access Journals (Sweden)

    Martínez Montañez, Mónica Liseth

    2012-10-01

    Full Text Available Objective: To study the mutagenic and genotoxic activities of particulate material (MP2,5 collected in Pamplona, Norte de Santander, Colombia.Materials and methods: MP2,5 was monitored by means of a Partisol 2025 sequential air sampler with Plus Palmflex quartz filters. The latter were subjected to two extraction procedures: Soxhlet extraction using dichloromethane-acetone; and ultrasonic extraction using dichloromethane, acetone and dichloromethane/ acetone mix. The mutagenic and genotoxic activities were determined for each extract.Results: This is the first study conducted in Colombia that reports the mutagenic and genotoxic activities associated with particulate matter (MP2,5 taken from vehicular emissions in Pamplona, Norte de Santander. The mutagenic assay determined by the Ames test using Salmonella typhimurium strains TA98 and TA100 showed a high direct mutagenic activity in the analyzed extracts. On the other hand, the genotoxic activity, determined by means of the comet assay, was high too.Conclusion: Particulate material (MP2,5 present in air samples in Pamplona (northeastern Colombia is a risk factor for the exposed population because it can directly induce mutations and also cause genotoxic damage.

  10. Mutagenic effect of ionizing radiation and chemical and environmental agents in Tradescantia

    International Nuclear Information System (INIS)

    Cebulska-Wasilewska, A.

    1988-01-01

    The studies covered the following problems: an influence of some environmental agents on the mutagenic effectiveness of ionizing radiation, interaction between ionizing radiation and chemical mutagens in the induction of somatic mutations and also an application of Tradescantia model system for biological monitoring. The studies showed that the pretreatment of Tradescantia plants with sodium fluoride or the modification of the soil composition with dolomite admixture, visibly influences plants radiosensitivity. The analysis of the changes in the dose-response curves suggested that the employed agents were influencing in different ways the repair processes of the DNA. The studies on the interaction between agents proved that the synergistic effect occurs in case of combined action of ionizing radiation with such chemical mutagens as ethyl methansulfonate or 1,2 dibromomethane. It was also discovered that in the range of low doses the effect was proportional to radiation dose and total exposition to chemical mutagen. The field application of Tradescantia method defined the mutagenicity of air pollution in the Cracow area. The highest frequencies of mutations were detected after the Chernobyl accident and after the damage of the filters in the Pharmaceutical Plant. The applied method was evaluated in respect of its usefulness for biological monitoring of environmental pollution. 163 refs. (author)

  11. Radionuclide toxicity in cultured mammalian cells: elucidation of the primary site of radiation damage

    International Nuclear Information System (INIS)

    Warters, R.L.; Hofer, K.G.; Harris, C.R.; Smith, J.M.

    1978-01-01

    Synchronized suspension cultures of Chinese hamster ovary cells (CHO) were labeled with various doses of 3 H-thymidine or 125 I-iododeoxyuridine to evaluate the cytocidal effects of intranuclear radionuclide decay. Damage produced by radionuclide decay outside the cell nucleus was studied on cells exposed to 125 I labeled, monovalent concanavalin A. After labeling, the cells were resynchronized in G 1 -phase and incubated for 36 h at 4 0 C to permit dose accumulation. Cell lethality was evaluated by the standard colony assay. Based on radionuclide incorporation data, cellular dimensions, and subcellular radionuclide distributions, the cumulative dose to whole cells, cell nuclei, and cellular cytoplasm was calculated from the known decay properties of 3 H and 125 I. (Auth.)

  12. Mutagenicity and co-mutagenicity of static magnetic field in SOD-deficient Escherichia coli

    International Nuclear Information System (INIS)

    Yoshie, Sachiko; Ikehata, Masateru; Hayakawa, Toshio; Hirota, Noriyuki; Takemura, Taro; Minowa, Takashi; Hanagata, Nobutaka

    2008-01-01

    The effects of strong static magnetic fields (SMFs) on mutagenesis related to reactive oxygen species were investigated. To estimate mutagenicity of SMFs, superoxide dismutase (SOD)-deficient Escherichia coli QC774 and its parental strain GC4468 were employed. Tester strains were exposed to 5, 10 and 13 T SMFs for 24 hr at 37 C degrees in LB medium. After exposure, mutation frequency on thymine synthesis genes was determined for evaluation of mutagenicity of SMFs exposure. In the result, no statistically significant difference in mutation frequency on thymine synthesis genes was observed between SMF-exposed cells and unexposed cells in all of magnetic flux densities. Furthermore, SMFs up to 13 T did not affect mutagenicity of plumbagine under its presence of 25 μM, respectively. It suggests that SMF did not have either mutagenicity or co-mutagenicity in SOD-deficient and its parental E. coli strains under the condition in this study. (author)

  13. Protein kinase CK2 localizes to sites of DNA double-strand break regulating the cellular response to DNA damage

    Directory of Open Access Journals (Sweden)

    Olsen Birgitte B

    2012-03-01

    Full Text Available Abstract Background The DNA-dependent protein kinase (DNA-PK is a nuclear complex composed of a large catalytic subunit (DNA-PKcs and a heterodimeric DNA-targeting subunit Ku. DNA-PK is a major component of the non-homologous end-joining (NHEJ repair mechanism, which is activated in the presence of DNA double-strand breaks induced by ionizing radiation, reactive oxygen species and radiomimetic drugs. We have recently reported that down-regulation of protein kinase CK2 by siRNA interference results in enhanced cell death specifically in DNA-PKcs-proficient human glioblastoma cells, and this event is accompanied by decreased autophosphorylation of DNA-PKcs at S2056 and delayed repair of DNA double-strand breaks. Results In the present study, we show that CK2 co-localizes with phosphorylated histone H2AX to sites of DNA damage and while CK2 gene knockdown is associated with delayed DNA damage repair, its overexpression accelerates this process. We report for the first time evidence that lack of CK2 destabilizes the interaction of DNA-PKcs with DNA and with Ku80 at sites of genetic lesions. Furthermore, we show that CK2 regulates the phosphorylation levels of DNA-PKcs only in response to direct induction of DNA double-strand breaks. Conclusions Taken together, these results strongly indicate that CK2 plays a prominent role in NHEJ by facilitating and/or stabilizing the binding of DNA-PKcs and, possibly other repair proteins, to the DNA ends contributing to efficient DNA damage repair in mammalian cells.

  14. Analysis of potential urban unstable areas and landslide-induced damages on Volterra historical site through a remote sensing approach

    Science.gov (United States)

    Del Soldato, Matteo; Bianchini, Silvia; Nolesini, Teresa; Frodella, William; Casagli, Nicola

    2017-04-01

    Multisystem remote sensing techniques were exploited to provide a comprehensive overview of Volterra (Italy) site stability with regards to its landscape, urban fabric and cultural heritage. Interferometric Synthetic Aperture Radar (InSAR) techniques allow precise measurements of Earth surface displacement, as well as the detection of building deformations on large urban areas. In the field of cultural heritage conservation Infrared thermography (IRT) provides surface temperature mapping and therefore detects various potential criticalities, such as moisture, seepage areas, cracks and structural anomalies. Between winter 2014 and spring 2015 the historical center and south-western sectors of Volterra (Tuscany region, central Italy) were affected by instability phenomena. The spatial distribution, typology and effect on the urban fabrics of the landslide phenomena were investigated by analyzing the geological and geomorphological settings, traditional geotechnical monitoring and advanced remote sensing data such as Persistent Scatterers Interferometry (PSI). The ground deformation rates and the maximum settlement values derived from SAR acquisitions of historical ENVISAT and recent COSMO-SkyMed sensors, in 2003-2009 and 2010-2015 respectively, were compared with background geological data, constructive features, in situ evidences and detailed field inspections in order to classify landslide-damaged buildings. In this way, the detected movements and their potential correspondences with recognized damages were investigated in order to perform an assessment of the built-up areas deformations and damages on Volterra. The IRT technique was applied in order to survey the surface temperature of the historical Volterra wall-enclosure, and allowed highlighting thermal anomalies on this cultural heritage element of the site. The obtained results permitted to better correlate the landslide effects of the recognized deformations in the urban fabric, in order to provide useful

  15. Repair of endogenous and ionizing radiation-induced DNA damages: mechanisms and biological functions

    International Nuclear Information System (INIS)

    Boiteux, S.

    2002-01-01

    The cellular DNA is continuously exposed to endogenous and exogenous stress. Oxidative stress due to cellular metabolism is the major cause of endogenous DNA damage. On the other hand, ionizing radiation (IR) is an important exogenous stress. Both induce similar DNA damages: damaged bases, abasic sites and strand breakage. Most of these lesions are lethal and/or mutagenic. The survival of the cell is managed by efficient and accurate DNA repair mechanisms that remove lesions before their replication or transcription. DNA repair pathways involved in the removal of IR-induced lesions are briefly described. Base excision repair (BER) is mostly involved in the removal of base damage, abasic sites and single strand breaks. In contrast, DNA double strand breaks are mostly repaired by non-homologous end joining (NHEJ) or homologous recombination (HR). How DNA repair pathways prevent cancer process is also discussed. (author)

  16. Mutagenic effect of cadmium on tetranucleotide repeats in human cells

    Energy Technology Data Exchange (ETDEWEB)

    Slebos, Robbert J.C. [Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States) and Department of Otolaryngology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States)]. E-mail: r.slebos@vanderbilt.edu; Li Ming [Department of Biostatistics, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States); Evjen, Amy N. [Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States); Coffa, Jordy [Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States); Shyr, Yu [Department of Biostatistics, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States); Yarbrough, Wendell G. [Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States); Department of Otolaryngology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States)

    2006-12-01

    Cadmium is a human carcinogen that affects cell proliferation, apoptosis and DNA repair processes that are all important to carcinogenesis. We previously demonstrated that cadmium inhibits DNA mismatch repair (MMR) in yeast cells and in human cell-free extracts (H.W. Jin, A.B. Clark, R.J.C. Slebos, H. Al-Refai, J.A. Taylor, T.A. Kunkel, M.A. Resnick, D.A. Gordenin, Cadmium is a mutagen that acts by inhibiting mismatch repair, Nat. Genet. 34 (3) (2003) 326-329), but cadmium also inhibits DNA excision repair. For this study, we selected a panel of three hypermutable tetranucleotide markers (MycL1, D7S1482 and DXS981) and studied their suitability as readout for the mutagenic effects of cadmium. We used a clonal derivative of the human fibrosarcoma cell line HT1080 to assess mutation levels in microsatellites after cadmium and/or N-methyl-N-nitro-N-nitrosoguanidine (MNNG) exposure to study effects of cadmium in the presence or absence of base damage. Mutations were measured in clonally expanded cells obtained by limiting dilution after exposure to zero dose, 0.5 {mu}M cadmium, 5 nM MNNG or a combination of 0.5 {mu}M cadmium and 5 nM MNNG. Exposure of HT1080-C1 to cadmium led to statistically significant increases in microsatellite mutations, either with or without concurrent exposure to MNNG. A majority of the observed mutant molecules involved 4-nucleotide shifts consistent with DNA slippage mutations that are normally repaired by MMR. These results provide evidence for the mutagenic effects of low, environmentally relevant levels of cadmium in intact human cells and suggest that inhibition of DNA repair is involved.

  17. Mutagenicity assessment of two herbal medicines, Urtan and Carmint in human leukocytes by single cell gel electrophoresis

    International Nuclear Information System (INIS)

    Jalili, M.; Hatami, A.; Kalantari, H.; Kalantar, E.

    2006-01-01

    The use of herbal medicine is an old and still widespread particle, which makes studies their genotoxicity essential. Urtan and Carmint are examples of herbal medicines used in Iran which used for the treatment of hyperplasia, diuretic, urinary diffusion and antispasmodic action, carminative gastrointestinal disfunction respectively. The aim of this study was to evaluate the mutagenicity of these herbal medicines in human leukocytes by Single Cell Gel Electrophoresis (SCGE). Both the herbal medicines were used at four concentrations (0.046, 0.092, 0.138 and 0.184/ 100 ml). The results were compared against positive (Cr VI) and negative (no mutagen) control groups. Fluorescence microscope was used to observe the DNA damage in randomly selected cells, which were stained with ethidium bromide. Microscopic observation of the affected cells due to Urtan and Carmint was encouraging as compared to previous studies using SCGE. Both Urtan and Carmint exhibited considerable DNA damage to the blood cells. For example, Urtan at o.184 g/100ml concentration had almost 23% mutagenic effect and as the concentration increased the mutagenic effect also increased. Similarly Carmint exhibited considerable DNA damage on blood cells. Therefore, both the herbal medicines may have some mutagenic effect. (author)

  18. Radiation exposure and health damage of residents at Semipalatinsk nuclear test site

    International Nuclear Information System (INIS)

    Tolebay, Rakhypbekov; Noso, Yoshihiro; Takechi, Nobuo

    2016-01-01

    Although the nuclear test site of Semipalatinsk (former Soviet Union and presently the Republic of Kazakhstan) stopped nuclear tests 25 years ago, there are presumably more than 200,000 victims near the site, including persons with a low dose and a high dose. Semey Medical University and Shimane University, together with the Kazakh Scientific Institute for Radiation Medicine and Ecology, have been conducting the measurement of radiation concentration of soil and the thyroid screening of residents. The following were surveyed: (1) chromosomal abnormality for 55 female residents (average 45 years in age) in heavily polluted areas and 25 female residents (average 42 years in age) in non-polluted areas, (2) mental abnormality of residents in polluted areas and non-polluted areas of Semey City, and (3) changes in the frequency of surgery cases for cancer between 1989 and 2014 at Semey Medical University Cancer Center. As for chromosomal abnormality, 3-5 times many mutation cases were observed in heavily polluted areas than in non-polluted areas. The nodules of thyroid gland were four times more frequent in heavily polluted areas. The frequency of a whole variety of cancers was nearly twice in polluted areas compared with in non-polluted areas, most of which were digestive system cancer, lung cancer, and breast cancer in the order. The frequency of mental abnormality has also increased nearly twice as compared to non-polluted areas, and it included neurological disorder, adjustment disorder, neuralgia, moderate depression, and learning disability. These results suggest that some physical effects can be caused by exposure. In the future, this study will investigate the effects of radiation exposure at the nuclear test site. (A.O.)

  19. Mutagens in urine of carbon electrode workers

    Energy Technology Data Exchange (ETDEWEB)

    Pasquini, R; Monarca, S; Sforzolini, G S; Conti, R; Fagioli, F

    1982-01-01

    Following previous work carried out in an Italian factory producing carbon electrodes and evaluating the occupational mutagenic-carcinogenic hazards, the authors studied the presence of mutagen metabolites in the urine of workers in the same factory who were exposed to petroleum coke and pitch and in the urine of a control group of unexposed workers. The urine samples were concentrated by absorption on XAD-2 columns and were tested using the Salmonella/microsome assay (strain TA98, TA100, TA1535, TA1538) with and without the addition of beta-glucuronidase and metabolizing system. The collection of urine samples was carried out twice, with an interval of 2 months; 'before working time', 'after working time', and also during Sunday. The results showed that urine samples collected 'before' occupational exposure (upon waking) or on Sunday revealed no mutagenic activity in either worker groups and that the urine samples collected after or during occupational exposure revealed high mutagenic activity in the exposed workers, with a statistically significant difference between the mean of the revertants/plate values for exposed and unexposed workers. On the basis of the previous and the present research, the authors suggest that application of the Salmonella/microsome test to work environments could offer useful and suitable tool for evaluating the health hazards due to mutagenic/carcinogenic substances from occupational exposure.

  20. Drug eruptions presenting at sites of prior radiation damage (sunlight and electron beam)

    International Nuclear Information System (INIS)

    Shelley, W.B.; Shelley, E.D.; Campbell, A.C.; Weigensberg, I.J.

    1984-01-01

    Two patients are described in whom sunburn and electron beam radiodermatitis, respectively, were critical determinants in localizing the initial presentation of drug eruptions. In the first instance, a severe sunburn of the back and thighs was followed 7 months later by the appearance of a toxic epidermal necrolysis drug reaction to trimethoprim-sulfamethoxazole in the exact sites of the previous bullous sunburn reaction. In the second patient, a radiodermatitis of the left upper arm due to electron beam therapy for metastatic breast cancer was followed 7 weeks later by a codeine drug reaction confined to the area of the radiodermatitis. In both instances, oral rechallenge with the offending drug reproduced the eruption

  1. Can Spirulina maxima reduce the mutagenic potential of sibutramine?

    Science.gov (United States)

    Araldi, R P; Santos, N P; Mendes, T B; Carvalho, L B; Ito, E T; de-Sá-Júnior, P L; Souza, E B

    2015-12-28

    The worldwide obesity pandemic requires the use of anti-obesity drugs. Sibutramine is an anti-obesity drug that has been used worldwide but is indiscriminately consumed in Brazil. Several studies have demonstrated that sibutramine promotes weight loss and weight maintenance, but several side effects have been associated with its systematic consumption. For this reason, sibutramine was withdrawn from the European and American markets, but still remains legal for use in Brazil. Studies have shown that a 5-10% reduction in body weight results in outstanding health benefits for obese patients. However, in order to promote significant weight loss, it is necessary to use sibutramine for at least 2 years. This long-term exposure has carcinogenic potential, as sibutramine causes DNA damage. Thus, this study evaluated the in vivo mutagenic potential of sibutramine alone (5, 7, 10, 15, and 20 mg/kg) and in association with Spirulina maxima (150 and 300 mg/kg), a cyanobacterium with antioxidant potential, using the polychromatic erythrocyte micronucleus test. Our results reinforced the mutagenic potential of sibutramine alone, which showed a time-dependent action. Combinatory treatments with S. maxima were not able to reduce the genotoxicity of sibutramine. These results were confirmed in vitro with the cytokinesis-blocked micronucleus test. In conclusion, our data showed that new alternative anti-obesity treatments are needed since the consumption of sibutramine can increase the risk of cancer in overweight patients.

  2. Mutagenicity evaluation of forty-one metal salts by the umu test.

    Science.gov (United States)

    Yamamoto, Akiko; Kohyama, Yuko; Hanawa, Takao

    2002-01-01

    Metallic biomaterials implanted in a human body may corrode and wear, releasing metal ions and debris which may induce adverse reactions such as inflammation, allergy, neoplastic formation, developmental malformation, etc. Mutagenicity is a very fundamental and important toxicity related to carcinogenicity and reproductive/developmental toxicity because the damages to genes or DNA can be a cause of carcinogenesis and developmental abnormalities. However, available mutagenic data on metallic ions and compounds are restricted to the number of elements. Therefore, to obtain the systematic data necessary for metal ion mutagenicity, 41 metal salts encompassing 36 metals and 5 metallic elements tested with different valences, were evaluated on their mutagenicity by a microbial test, the umu test. As a result, K(2)Cr(2)O(7), RhCl(3), IrCl(4), and MgCl(2) are positive without metabolic activation. Concentrations having the maximum mutagenic effect (C(max)) are 9.65 x 10(-5), 1.00 x 10(-4), 3.11 x 10(-3), 4.12 x 10(-3) mol. L(-1), respectively. CuCl(2), VCl(3), CuCl, RhCl(3), K(2)Cr(2)O(7), and IrCl(4) are positive with metabolic activation by S-9 mix with C(max) of 1.60 x 10(-5), 3.91 x 10(-5), 1.57 x 10(-4), 2.00 x 10(-4), 3.86 x 10(-4), 1.56 x 10(-2) mol. L(-1), respectively. Thirty-five metal salts were negative for tests performed both with and without metabolic activation, whereas it was impossible to evaluate the mutagenicity of MoCl(5) and ZrCl(4) by the umu test because of their colorimetric reaction to testing reagents. Copyright 2001 John Wiley & Sons, Inc.

  3. THE GENOTOXICITY OF AMBIENT OUTDOOR AIR, A REVIEW: SALMONELLA MUTAGENICITY

    Science.gov (United States)

    The genotoxicity of ambient outdoor air, a review: Salmonella mutagenicityAbstractMutagens in urban air pollution come from anthropogenic sources (especially combustion sources) and are products of airborne chemical reactions. Bacterial mutation tests have been used ...

  4. Concept and methodology for evaluating core damage frequency considering failure correlation at multi units and sites and its application

    Energy Technology Data Exchange (ETDEWEB)

    Ebisawa, K.; Teragaki, T.; Nomura, S. [Former Incorporated Administrative Agency, Japan Nuclear Safety Organization (Japan); Abe, H., E-mail: Hiroshi_abe@nsr.go.jp [Former Incorporated Administrative Agency, Japan Nuclear Safety Organization (Japan); Shigemori, M.; Shimomoto, M. [Mizuho Information & Research Institute, 2-3, Kanda-Nishikicho, Chiyoda-ku, Tokyo (Japan)

    2015-07-15

    Highlights: • We develop a method to evaluate CDF considering failure correlation at multi units. • We develop a procedure to evaluate correlation coefficient between multi components. • We evaluate CDF at two different BWR units using correlation coefficients. • We confirm the validity of method and correlation coefficient through the evaluation. - Abstract: The Tohoku earthquake (Mw9.0) occurred on March 11, 2011 and caused a large tsunami. The Fukushima Daiichi Nuclear Power Plant with six units were overwhelmed by the tsunami and core damage occurred. Authors proposed the concept and method for evaluating core damage frequency (CDF) considering failure correlation at the multi units and sites. Based on the above method, one of authors developed the procedure for evaluating the failure correlation coefficient and response correlation coefficient between the multi components under the strong seismic motion. These method and failure correlation coefficients were applied to two different BWR units and their CDF was evaluated by seismic probabilistic risk assessment technology. Through this quantitative evaluation, the validity of the method and failure correlation coefficient was confirmed.

  5. Concept and methodology for evaluating core damage frequency considering failure correlation at multi units and sites and its application

    International Nuclear Information System (INIS)

    Ebisawa, K.; Teragaki, T.; Nomura, S.; Abe, H.; Shigemori, M.; Shimomoto, M.

    2015-01-01

    Highlights: • We develop a method to evaluate CDF considering failure correlation at multi units. • We develop a procedure to evaluate correlation coefficient between multi components. • We evaluate CDF at two different BWR units using correlation coefficients. • We confirm the validity of method and correlation coefficient through the evaluation. - Abstract: The Tohoku earthquake (Mw9.0) occurred on March 11, 2011 and caused a large tsunami. The Fukushima Daiichi Nuclear Power Plant with six units were overwhelmed by the tsunami and core damage occurred. Authors proposed the concept and method for evaluating core damage frequency (CDF) considering failure correlation at the multi units and sites. Based on the above method, one of authors developed the procedure for evaluating the failure correlation coefficient and response correlation coefficient between the multi components under the strong seismic motion. These method and failure correlation coefficients were applied to two different BWR units and their CDF was evaluated by seismic probabilistic risk assessment technology. Through this quantitative evaluation, the validity of the method and failure correlation coefficient was confirmed

  6. Spore membrane(s) as the site of damage within heated Clostridium perfringens spores.

    Science.gov (United States)

    Flowers, R S; Adams, D M

    1976-02-01

    Clostridium perfringens spores were injured by ultrahigh-temperature treatment at 105 C for 5 min. Injury was manifested as an increased sensitivity to polymyxin and neomycin. Since many of the survivors could not germinate normally the ultrahigh-temperature-treated spores were sensitized to and germinated by lysozyme. Polymyxin reportedly acts upon the cell membrane. Neomycin may inhibit protein synthesis and has surface-active properties. Injured spores were increasingly sensitive to known surface-active agents, sodium lauryl sulfate, sodium deoxycholate, and Roccal, a quaternary ammonium compound. Injured spores sensitive to polymyxin and neomycin also were osmotically fragile and died during outgrowth in a liquid medium unless the medium was supplemented with 20% sucrose, 10% dextran, or 10% polyvinylpyrrolidone. The results suggested that a spore structure destined to become cell membrane or cell wall was the site of injury. Repair of injury during outgrowth in the presence of protein, deoxyribonucleic acid, ribonucleic acid and cell wall synthesis inhibitors was consistent with this hypothesis.

  7. Mutagens and carcinogens in foods. Epidemiologic review.

    OpenAIRE

    Hislop, T. G.

    1993-01-01

    Evidence that diet contributes to the development of cancer is strengthening. This paper examines mutagens and carcinogens, such as naturally occurring substances, products of cooking and food processing, intentional and unintentional additives, and contaminants, found in foods. Such substances are present in minute quantities in the diets of average Canadians. Indication of health risk is largely limited to experimental laboratory evidence.

  8. Mutagens and carcinogens in foods. Epidemiologic review.

    Science.gov (United States)

    Hislop, T. G.

    1993-01-01

    Evidence that diet contributes to the development of cancer is strengthening. This paper examines mutagens and carcinogens, such as naturally occurring substances, products of cooking and food processing, intentional and unintentional additives, and contaminants, found in foods. Such substances are present in minute quantities in the diets of average Canadians. Indication of health risk is largely limited to experimental laboratory evidence. PMID:8499796

  9. Simultaneous Determination of Mutagenicity and Toxicity of ...

    African Journals Online (AJOL)

    A demonstration of cytotoxicity is required (measurement of cell number, culture confluency and inhibition of mitotic index) for in vitro cytogenetic assays. The study therefore investigated whether delayed cytotoxicity can be used to simultaneously predict mutagenicity and cytotoxicty. Chinese hamster lung cells were ...

  10. Synthesis and radiolabeling of heterocyclic food mutagens

    International Nuclear Information System (INIS)

    Rapoport, H.; Waterhouse, A.L.; Thompson, C.M.; O'Connell, J.F.

    1986-01-01

    The imidazoquinoline and imidazoquinoxaline food mutagens found in cooked meat are being synthesized by unambiguous methods that allow for the preparation of sufficient quantities of material for biological studies. These methods avoid difficult separations of regioisomeric mixtures of products and are designed to allow incorporation of specific high level tritium labeling

  11. Predictive Models for Carcinogenicity and Mutagenicity ...

    Science.gov (United States)

    Mutagenicity and carcinogenicity are endpoints of major environmental and regulatory concern. These endpoints are also important targets for development of alternative methods for screening and prediction due to the large number of chemicals of potential concern and the tremendous cost (in time, money, animals) of rodent carcinogenicity bioassays. Both mutagenicity and carcinogenicity involve complex, cellular processes that are only partially understood. Advances in technologies and generation of new data will permit a much deeper understanding. In silico methods for predicting mutagenicity and rodent carcinogenicity based on chemical structural features, along with current mutagenicity and carcinogenicity data sets, have performed well for local prediction (i.e., within specific chemical classes), but are less successful for global prediction (i.e., for a broad range of chemicals). The predictivity of in silico methods can be improved by improving the quality of the data base and endpoints used for modelling. In particular, in vitro assays for clastogenicity need to be improved to reduce false positives (relative to rodent carcinogenicity) and to detect compounds that do not interact directly with DNA or have epigenetic activities. New assays emerging to complement or replace some of the standard assays include VitotoxTM, GreenScreenGC, and RadarScreen. The needs of industry and regulators to assess thousands of compounds necessitate the development of high-t

  12. Mutagenic interactions between near-ultraviolet (365 nm) radiation and alkylating agents in Escherichia coli

    International Nuclear Information System (INIS)

    Moraes, E.C. de; Tyrell, R.M.

    1981-01-01

    The mutagenic interaction between near-ultrviolet (365 nm) radiation and the alkylting agents ehtyl methanesulponate (EMS) and methyl methanesulphonate (MMS) was studied in a repair-component and an excision-deficient stram of Escherichia coli. Near-UV raditation modified the metabolic response of of exposure to these chemicals and either reduced or increased their mutagenic efficiency. Based on these results, an experimental model was formulated to explain the mutagenic interactions that occur between near-UV and various agents that induce prototrophic reverants cia error-prone repair of DNA. According to this model, low doses of near-UV provoke conditions for mutation frequency decline (MFI) and lead to a mutagenic antagonism. With increasing near-Uv doses, damage to constitutive error-free repairs system increases, favouring the error-prone system and inhibiting the MFD. Under these conditions there will be a progressive decrease in antagonism until at high doses an enhancement of mutation frequency (positive interaction) will occur. (orig.)

  13. Mutagenicity and antimutagenicity of Baccharis dracunculifolia extract in chromosomal aberration assays in Chinese hamster ovary cells.

    Science.gov (United States)

    Munari, Carla Carolina; Resende, Flávia Aparecida; Alves, Jacqueline Morais; de Sousa, João Paulo; Bastos, Jairo Kenupp; Tavares, Denise Crispim

    2008-09-01

    Baccharis dracunculifolia De Candole (Asteraceae), a native plant from the Brazilian "cerrado", is widely used in folk medicine as an anti-inflammatory agent and for the treatment of gastrointestinal diseases. B. dracunculifolia has been described as the most important plant source of propolis in southeastern Brazil, which is called green propolis due to its color. The aim of the present study was to evaluate the mutagenic and antimutagenic effects of the ethyl acetate extract of B. dracunculifolia leaves (Bd-EAE) on Chinese hamster ovary cells. On one hand, the results showed a significant increase in the frequencies of chromosome aberrations at the highest Bd-EAE concentration tested (100 microg/mL). On the other hand, the lowest Bd-EAE concentration tested (12.5 micro/mL) significantly reduced the chromosome damage induced by the chemotherapeutic agent doxorubicin. The present results indicate that Bd-EAE has the characteristics of a so-called Janus compound, that is, Bd-EAE is mutagenic at higher concentrations, whereas it displays a chemopreventive effect on doxorubicin-induced mutagenicity at lower concentrations. The constituents of B. dracunculifolia responsible for its mutagenic and antimutagenic effects are probably flavonoids and phenylpropanoids, since these compounds can act either as pro-oxidants or as free radical scavengers depending on their concentration.

  14. Mutagenic effect of cyclophosphan on bone marrow cells of irradiated rats

    International Nuclear Information System (INIS)

    Barkan, R.S.; Yakovleva, T.K.

    1979-01-01

    The frequency of chromosome aberrations in bone marrow cells of male rats was studied 24 hours after the intraperitoneal injection of cyclophosphane (25 mg/kg weight). Cyclophosphane (CP) was injected to animals that had been earlier (15 days before, 1, 3, 4, 6 and 9 months earlier) exposed to X-ray and γ-irradiation at the dose of 400 rad. It has been shown that the preliminary irradiation of animals results in a higher mutagenic CP effect as against its effect for non irradiated rats. The effect was recorded during four months following the acute single x-irradiation (dose rate of 70 rad/min) and within one month following chronic γ-irradiation (dose rate of 100 rad/day). At later periods, the above effect fully disappeared. Chronic irradiation was less effective with regard to the subsequent mutagenic CP action than the acute irradiation. In most experiments with acute irradiation an increase in mutagenic CP efficiency revealed itself both in an increase in the frequency of cells with chromosome aberrations and in the cell damage rate. The possible mechanisms of the effect of preliminary irradiation on the subsequent mutagenic effect of chemical compounds are discussed

  15. In vivo and in vitro evaluation of the mutagenic potential of carbamazepine: does melatonin have anti-mutagenic activity?

    Science.gov (United States)

    Awara, W M; El-Gohary, M; El-Nabi, S H; Fadel, W A

    1998-01-16

    The mutagenic potential of carbamazepine (CBZ) therapy has been evaluated both in vivo and in vitro. Analysis of chromosome aberrations (CA), sister chromatid exchanges (SCEs), mitotic and proliferation indices (PRI) were performed. The in vivo study was carried out on 30 patients with idiopathic epilepsy end undergoing treatment with CBZ for different periods starting from 6 months up to 15 years. Plasma CBZ levels were also determined for each patient. The results showed that the total CA and SCEs were significantly increased in CBZ-treated patients. There was no significant correlation between CA and either duration of treatment or the plasma CBZ levels for each patient. The mitotic and proliferation indices were found to be slightly but non-significantly decreased compared to control values. On the other hand, in vitro analysis showed a significant dose-dependent increase in CA and SCEs in human lymphocyte cultures treated with CBZ (4-12 microg/ml). The mitotic and proliferation indices were also found to be decreased but only significantly in case of high doses of CBZ (12 microg/ml). Pretreatment of human lymphocytes with melatonin (0.5 mM) exhibited a significant decrease in the frequencies of CBZ-induced CA and SCEs as compared with non-treated cultures. The depressed mitotic and proliferation indices were also found to be improved in cultures pretreated with melatonin. In conclusion, these observations suggest that CBZ monotherapy may lead to chromosome damaging effects (genotoxic) and the use of melatonin as anti-mutagenic agent for human protection against CBZ-induced chromosome damage should be considered.

  16. Single cell gel electrophoresis as a tool to assess genetic damage in Heleobia cf. australis (Mollusca: Gastropoda as sentinel for industrial and domestic pollution in Montevideo bay (Uruguay

    Directory of Open Access Journals (Sweden)

    Silvia Villar

    2015-09-01

    Full Text Available AbstractThe knowledge of the extent of DNA damage in aquatic organisms in polluted areas is an important issue because contamination may alter their health at sublethal levels. Although molluscs have been widely used to monitor water pollution, there are no records of in vivo genotoxicity studies. Heleobia cf. australis, is distributed in almost all Uruguayan coastal ecosystems, including highly polluted sites. The comet assay is a damage genetic biomarker based on the migration of negatively charged DNA fragments produced by mutagenic agents in individual cells. Live individuals were collected in the Montevideo Bay (impacted area and Laguna Garzón (control to analyze the presence of mutagenic agents in the former site through comet assay. Cells from organisms of the impacted area showed significantly higher levels of genetic damage than those obtained in the control population, measured by percentage of DNA in the tail. Although preliminary, this approach supports the idea that H. cf. australis could be used as a sentinel to evaluate the presence of mutagenic agents in estuarine environments, alerting to the impact of contamination in its early stages.

  17. Chemistry of mutagens and carcinogens in broiled food.

    Science.gov (United States)

    Nishimura, S

    1986-01-01

    From a chemical point of view, the following subjects are important areas in studies on mutagens and carcinogens in broiled foods. In addition to heterocyclic amines which need microsomal activation, the structural elucidation of more labile direct-acting mutagens is necessary. It is known that there are still various unknown minor mutagens in broiled foods. Although the structural characterization of such compounds is more difficult, it is important since they might be hazardous in spite of their low mutagenicity. A more feasible and easier method for quantitative analysis of mutagens, in addition to HPLC and GC/MS methods presently employed, must be developed. The mechanism of formation of mutagens by broiling of food should be studied. An effective chemical method to prevent formation of mutagens or to destroy them, once formed, should be developed. PMID:3757944

  18. Probe for the mutagenic activity of the carcinogen 4-aminobiphenyl: synthesis and characterization of an M13mp10 genome containing the major carcinogen-DNA adduct at a unique site

    International Nuclear Information System (INIS)

    Lasko, D.D.; Basu, A.K.; Kadlubar, F.F.; Evans, F.E.; Lay, J.O. Jr.; Essigmann, J.M.

    1987-01-01

    The duplex genome of Escherichia coli virus M13mp10 was modified at a unique site to contain N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG/sup 8-ABP/), the major carcinogen-DNA adduct of the human bladder carcinogen 4-aminobiphenyl. A tetradeoxynucleotide containing a single dG/sup 8-ABP/ residue was synthesized by reacting 5'-d(TpGpCpA)-3' with N-acetoxy-N-(trifluoroacetyl)-4-aminobiphenyl, followed by high-performance liquid chromatography purification of the principal reaction product 5'-d(TpG/sup 8-ABP/pCpA)-3' (yield 15-30%). Characterization by fast atom bombardment mass spectrometry confirmed the structure as an intact 4-aminobiphenyl-modified tetranucleotide, while 1 H nuclear magnetic resonance spectroscopy established the site of substitution and the existence of ring stacking between the carcinogen residue and DNA bases. Experiments in which the tetranucleotides were 5' end labeled with [ 32 P]phosphate revealed the following: 1)the adducted oligomer, when incubated in a 1000-fold molar excess in the presence of T4 DNA ligase and ATP, was found to be incorporated into the gapped DNA molecules with an efficiency of approximately 30%, as compared to the unadducted d(pTpGpCpA), which was incorporated with 60% ligation efficiency; 2)radioactivity from the 5' end of each tetranucleotide was physically mapped to a restriction fragment that contained the PstI site and represented 0.2% of the genome; 3) the presence of the lesion within the PstI recognition site inhibited the ability of PstI to cleave the genome at this site; 4)in genomes in which ligation occurred, T4 DNA ligase was capable of covalently joining both modified and unmodified tetranucleotides to the gapped structures on both the 5' and the 3' ends with at least 90% efficiency. On the basis of these and other data, the dG/sup 8-ABP/-modified genome was judged to be a useful probe for investigation of site-specific mutagenesis in E. coli

  19. Molecular Modeling of the Major DNA Adduct Formed from Food Mutagen Ochratoxin A in NarI Two-Base Deletion Duplexes: Impact of Sequence Context and Adduct Ionization on Conformational Preference and Mutagenicity.

    Science.gov (United States)

    Kathuria, Preetleen; Sharma, Purshotam; Manderville, Richard A; Wetmore, Stacey D

    2017-08-21

    Exposure to ochratoxin A (OTA), a possible human carcinogen, leads to many different DNA mutations. As a first step toward understanding the structural basis of OTA-induced mutagenicity, the present work uses a robust computational approach and a slipped mutagenic intermediate model previously studied for C 8 -dG aromatic amine adducts to analyze the conformational features of postreplication two-base deletion DNA duplexes containing OT-dG, the major OTA lesion at the C 8 position of guanine. Specifically, a total of 960 ns of molecular dynamics simulations (excluding trial simulations) were carried out on four OT-dG ionization states in three sequence contexts within oligomers containing the NarI recognition sequence, a known hotspot for deletion mutations induced by related adducts formed from known carcinogens. Our results indicate that the structural properties and relative stability of the competing "major groove" and "stacked" conformations of OTA adducted two-base deletion duplexes depend on both the OTA ionization state and the sequence context, mainly due to conformation-dependent deviations in discrete local (hydrogen-bonding and stacking) interactions at the lesion site, as well as DNA bending. When the structural characteristics of the OT-dG adducted two-base deletion duplexes are compared to those associated with previously studied C 8 -dG adducts, a greater understanding of the effects of the nucleobase-carcinogen linkage, and size of the carcinogenic moiety on the conformational preferences of damaged DNA is obtained. Most importantly, our work predicts key structural features for OT-dG-adducted deletion DNA duplexes, which in turn allow us to develop hypotheses regarding OT-dG replication outcomes. Thus, our computational results are valuable for the design and interpretation of future biochemical studies on the potentially carcinogenic OT-dG lesion.

  20. Studies on tritium (tritiated water) mutagenicity and teratogenicity in rats

    International Nuclear Information System (INIS)

    Yagova, A.Kh.

    1979-01-01

    Single parental exposures to a range of tritium (tritiated water) activities, injecterd intraperitoneally, were used to study induction of genetic damage and effects on prenatal development in rats. In the male, treatment of postmeiotic stages of spermatogenesis was found to produce genetic damage, as judged by the dominant lethality test, at activity levels of the order of 1.0 microcurie/g body weight and above; when treating spermatogonia, no genetic damage was detected by this test. In the female, induced dominant lethality was observed after exposing oocytes in growing follicles to a tritium activity level of 10 microcurie/g b.w. Cytogenetic analysis of spermatocytes in meiosis disclosed increased frequency of reciprocal translocations after exposure of premeiotic cells (spermatogonia) to activities above 7 microcurie/g b.w., the effect tending to rise with increase in activity aministered per gram of body weight. Maternal treatment during early pregnancy was shown to raise prenatal death rate only at activities above 0.1 microcurie/g b.w; with such low activities, no discernible effects on postnatal development were noted, judging by postnatal death rate and increase in offspring body weight with time. In conclusion, experimental evidence was obthained that a tritiated water activity level of 0.1 microcurie per gram body weight (which is one order of magnitude above the annual limit of intake of tritiated water for members of the public) appears to produce no mutagenic effect and exert no influence upon the embryo

  1. Urinary 1-hydroxypyrene and mutagenicity in bus drivers and mail carriers exposed to urban air pollution in Denmark

    DEFF Research Database (Denmark)

    Hansen, Åse Marie; Wallin, Håkan; Binderup, Mona Lise

    2004-01-01

    BACKGROUND: Previous studies in Denmark have shown that bus drivers and tramway employees were at an increased risk for developing several types of cancer and that bus drives from central Copenhagen have high levels of biomarkers of DNA damage.AIMS: The present study evaluates 1-hydroxypyrene....../mol creatinine [CI: 0.37-1.47] and female bus drivers 1.90 revertants/mol creatinine [CI: 1.01-2.79] higher mutagenic activity in urine than mail carriers. CONCLUSION: The present study indicates that bus drivers are more exposed to polycyclic aromatic hydrocarbons (PAH) and mutagens than mail carriers. Mail...

  2. Economic Valuation of On Site Material Damages of High Water on Economic Activities based in the City of Venice: Results from a Dose-Response-Expert-Based Valuation Approach

    OpenAIRE

    Paulo A.L.D. Nunes; Margaretha Breil; Gretel Gambarelli

    2005-01-01

    The paper focuses on the economic assessment of damages caused by high water in the city of Venice. In particular, we focus our attention on a valuation exercise that addresses the estimation of monetary, short period, on-site damages due to high water events on the different business activities located in Venice. On-site damages include both mitigation costs, which refer to all types of financial expenditure undergone to avert physical and material damages caused by flooding, and remediation...

  3. FANCI Regulates Recruitment of the FA Core Complex at Sites of DNA Damage Independently of FANCD2.

    Directory of Open Access Journals (Sweden)

    Maria Castella

    2015-10-01

    Full Text Available The Fanconi anemia (FA-BRCA pathway mediates repair of DNA interstrand crosslinks. The FA core complex, a multi-subunit ubiquitin ligase, participates in the detection of DNA lesions and monoubiquitinates two downstream FA proteins, FANCD2 and FANCI (or the ID complex. However, the regulation of the FA core complex itself is poorly understood. Here we show that the FA core complex proteins are recruited to sites of DNA damage and form nuclear foci in S and G2 phases of the cell cycle. ATR kinase activity, an intact FA core complex and FANCM-FAAP24 were crucial for this recruitment. Surprisingly, FANCI, but not its partner FANCD2, was needed for efficient FA core complex foci formation. Monoubiquitination or ATR-dependent phosphorylation of FANCI were not required for the FA core complex recruitment, but FANCI deubiquitination by USP1 was. Additionally, BRCA1 was required for efficient FA core complex foci formation. These findings indicate that FANCI functions upstream of FA core complex recruitment independently of FANCD2, and alter the current view of the FA-BRCA pathway.

  4. Computational study of hydration at the TD damaged site of DNA in complex with repair enzyme T4 endonuclease V

    International Nuclear Information System (INIS)

    Pinak, Miroslav

    2000-02-01

    An analysis of the distribution of water around DNA surface focusing on the role of the distribution of water molecules in the proper recognition of damaged site by repair enzyme T4 Endonuclease V was performed. The native DNA dodecamer, dodecamer with the thymine dimer (TD) and complex of DNA and part of repair enzyme T4 Endonuclease V were examined throughout the 500 ps of molecular dynamics simulation. During simulation the number of water molecules close to the DNA atoms and the residence time were calculated. There is an increase in number of water molecules lying in the close vicinity to TD if compared with those lying close to two native thymines (TT). Densely populated area with water molecules around TD is one of the factors detected by enzyme during scanning process. The residence time was found higher for molecule of the complex and the six water molecules were found occupying the stabile positions between the TD and catalytic center close to atoms P, C3' and N3. These molecules originate water mediated hydrogen bond network that contribute to the stability of complex required for the onset of repair process. (author)

  5. Computational study of hydration at the TD damaged site of DNA in complex with repair enzyme T4 endonuclease V

    Energy Technology Data Exchange (ETDEWEB)

    Pinak, Miroslav [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2000-02-01

    An analysis of the distribution of water around DNA surface focusing on the role of the distribution of water molecules in the proper recognition of damaged site by repair enzyme T4 Endonuclease V was performed. The native DNA dodecamer, dodecamer with the thymine dimer (TD) and complex of DNA and part of repair enzyme T4 Endonuclease V were examined throughout the 500 ps of molecular dynamics simulation. During simulation the number of water molecules close to the DNA atoms and the residence time were calculated. There is an increase in number of water molecules lying in the close vicinity to TD if compared with those lying close to two native thymines (TT). Densely populated area with water molecules around TD is one of the factors detected by enzyme during scanning process. The residence time was found higher for molecule of the complex and the six water molecules were found occupying the stabile positions between the TD and catalytic center close to atoms P, C3' and N3. These molecules originate water mediated hydrogen bond network that contribute to the stability of complex required for the onset of repair process. (author)

  6. [Mutagenicity of radon and radon daughters

    International Nuclear Information System (INIS)

    1990-01-01

    The current objective of our research is to investigate the dose-response relationship of the lethal and mutagenic effects of exposure of cells to radon and its decay products. Dose-rate dependence will be studied, as well as the nature of the DNA lesions. The effect of DNA repair on the lethal and mutagenic effects of exposure and on the character of the DNA lesions will be investigated by comparing the response of L5178Y strains which differ in their ability to rejoin X radiation-induced DNA double-strand breaks. This report discusses progress incurred from 4/1/1988--10/1/1990. 5 refs., 9 figs., 6 tabs

  7. Mutagenicity potential of commercial broth cubes at varying concentrations

    International Nuclear Information System (INIS)

    De Torres, Nelson Velasquez; Talain, Augusto Nicolas.

    1997-01-01

    Today, there has been a growing concern on the mutagenicity potential of environmental chemical systems. These environmental chemicals such as pesticides, food additives, synthetic drugs, water and atmospheric pollutants are possible causes of mutagenic activity. Meat products and some meat flavorings, were also reported to exhibit mutagenic activity. And since these products are normal part of the daily human diet, there is a need for extensive studies regarding the possible mutagenic activity associated with these products. This study aimed to evaluate the mutagenicity potential of commercial broth cubes at varying concentration. The researchers sought to answer the following questions: 1. Do beef, pork and chicken broth cubes exhibit mutagenic activity? 2. Are there significant differences in the mutagenic activity among the three samples? 3. Are these significant differences in the mutagenic activity exhibited by each of the samples compared to that of Mitomycin-C (positive control)? 4. Which of the sample of each specific concentration exhibit the greatest mutagenic activity? Three specific concentrations of beef, pork and chicken broth cubes were prepared and their mutagenicity potential was evaluated by using the Micronucleus test. The formation of micro nucleated polychromatic and micro nucleated normo chromatic erythrocytes in bone marrow cells of mice treated with these samples were detected using a Carl-Zeiss photo microscope. The statistical tool used to test the validity of the null hypothesis was analysis of variance using randomized complete block design and independent T- test. (author)

  8. Mutagenicity potential of commercial broth cubes at varying concentrations

    Energy Technology Data Exchange (ETDEWEB)

    De Torres, Nelson Velasquez; Talain, Augusto Nicolas

    1998-12-31

    Today, there has been a growing concern on the mutagenicity potential of environmental chemical systems. These environmental chemicals such as pesticides, food additives, synthetic drugs, water and atmospheric pollutants are possible causes of mutagenic activity. Meat products and some meat flavorings, were also reported to exhibit mutagenic activity. And since these products are normal part of the daily human diet, there is a need for extensive studies regarding the possible mutagenic activity associated with these products. This study aimed to evaluate the mutagenicity potential of commercial broth cubes at varying concentration. The researchers sought to answer the following questions: 1. Do beef, pork and chicken broth cubes exhibit mutagenic activity? 2. Are there significant differences in the mutagenic activity among the three samples? 3. Are these significant differences in the mutagenic activity exhibited by each of the samples compared to that of Mitomycin-C (positive control)? 4. Which of the sample of each specific concentration exhibit the greatest mutagenic activity? Three specific concentrations of beef, pork and chicken broth cubes were prepared and their mutagenicity potential was evaluated by using the Micronucleus test. The formation of micro nucleated polychromatic and micro nucleated normo chromatic erythrocytes in bone marrow cells of mice treated with these samples were detected using a Carl-Zeiss photo microscope. The statistical tool used to test the validity of the null hypothesis was analysis of variance using randomized complete block design and independent T- test. (author). 28 refs., 9 figs., 26 tabs.

  9. Different damage observed in the villages of Pescara del Tronto and Vezzano after the M6.0 August 24, 2016 central Italy earthquake and site effects analysis

    Directory of Open Access Journals (Sweden)

    Angelo Masi

    2017-01-01

    Full Text Available The authors have surveyed many damaged villages located at the epicentre of the ML=6.0 earthquake which occurred on August 24, 2016 in central Italy. Some unexpected anomalies were discovered such as very different levels of damage in Vezzano and Pescara del Tronto villages (Arquata del Tronto Municipality, Ascoli Piceno province. The two villages are situated just 1300 meters from each other. Pescara del Tronto suffered very heavy damage with many masonry building collapses and 48 fatalities, while Vezzano suffered only light damage to few buildings. This paper provides a preliminar analysis from an engineering and geophysics perspective. Particularly, rapid visual surveys were carried out in the two villages in order to detect possible significant differences in the vulnerability of their building stocks and site geophysical investigations were performed to detect possible local amplification effects.

  10. Space mutagenic effect of Trichoderma reesei

    International Nuclear Information System (INIS)

    Tian Xingshan; Zhou Fengzheng; Huang Xiaoguang; Kuang Zheshi; Pan Mushui; Li Guoli; Guo Yong

    2005-01-01

    The slant mycelia cultured with or without mutagenic agent diethyl sulfate (DS) and spores of Trichoderma reesei were loaded in the 18th returning satellite. Systematical screening showed that the life cycle and morphology of some strains had changed after space flight. After selection and domestication, 3 mutant strains with high cellulose enzyme activity were isolated. The cellulose enzyme productivities of the mutants were significantly increased more than 50%, and the mutant were generically stable. (authors)

  11. Mutagenic DNA repair in Escherichia coli. VII

    International Nuclear Information System (INIS)

    Bridges, B.A.; Mottershead, R.P.

    1978-01-01

    Incubation of E. coli WP2 in the presence of chloramphenicol (CAP) for 90 min before and 60 min after γ-irradiation had no effect on the induction of Trp + mutations. Bacteria that had been treated with CAP for 90 min prior to UV irradiation showed normal or near normal yields of induced mutations to streptomycin or colicin E2 resistance. Most of these mutations lost their photoreversibility (indicating 'fixation') during continued incubation with CAP for a further 60 min after irradiation, during which time neither protein nor DNA synthesis was detectable. It is suggested that CAP-sensitive protein synthesis is not required for mutagenic (error-prone) repair of lesions in pre-existing DNA, arguing against an inducible component in this repair. In contrast the frequency of UV-induced mutations to Trp + (largely at suppressor loci) was drastically reduced by CAP pretreatment, confirming the need for an active replication fork for UV-mutagenesis at these loci. It is known from the work of others that CAP given after UV abolishes mutagenesis at these loci. It is concluded that CAP-sensitive protein synthesis (consistent with a requirement for an inducible function) is necessary for mutagenic repair only in newly-replicated DNA (presumably at daughter strand gaps) and not in pre-existing DNA. The data are consistent with but do not prove the hypothesis that CAP-sensitive and insensitive modes of mutagenesis reflect minor differences in the operation of a single basic mutagenic repair system. (Auth.)

  12. Using the Salmonella assay to delineate the dispersion routes of mutagenic compounds from coal wastes in contaminated soil.

    Science.gov (United States)

    da Silva Júnior, Flavio Manoel Rodrigues; Vargas, Vera Maria Ferrão

    2009-03-17

    The mutagenicity of acidic and organic extracts of surface soil under the influence of a coal-fired power plant was evaluated by Salmonella/microsome assay using strains TA97a, TA98 and TA100 in the absence and presence of exogenous metabolic systems (S9 mix). Additionally, strains YG1041 and YG1042 (sensitive to nitroderivatives) were used for the organic extracts. In general, the responses were higher in the organic extracts in the presence of S9 mix. The comparison between strains TA98 and TA100 and their derived strains YG1041 and YG1042, respectively, allowed the detection of the presence of nitro-aromatic compounds in some sampling areas, which was confirmed by chemical analysis. The interpretation of the set of mutagenesis data suggests that there are two important mutagenic compound dispersion routes in the area of study: frameshift mutagens were dispersed predominantly by runoff and leaching, while base-pair substitution mutagens were dispersed mainly by the atmosphere. This mutagenic damage might be attributed to the effects of several substances detected in the area, such as aliphatic hydrocarbons and the metals aluminum, cadmium, lead and iron.

  13. Radiation-induced mutagenicity and lethality in Ames tester strains of Salmonella

    International Nuclear Information System (INIS)

    Isildar, M.; Bakale, G.

    1984-01-01

    Mutation and killing induced by X radiation and 60 Co γ radiation were studied in six different histidine-requiring auxotrophs of Salmonella typhimurium. Strain TA100, which is sensitive to base-pair substitutions, and strains TA2637 and TA98, which are sensitive to frameshifts, carry the pKM101 plasmid and exhibit significantly higher radiation-induced mutations compared to their plasmidless parent strains TA1535, TA1537, and TA1538, respectively. Among the plasmid-containing strains, TA98 and TA2637 are much more sensitive to the mutagenic action of radiation than is TA100 based on a comparison with their respective spontaneous mutation rates; however, no uniformity was observed in the responses of the strains to the lethal action of ionizing radiation. The following conclusions are consistent with these observations: (1) the standard Ames Salmonella assay correctly identifies ionizing radiation as a mutagenic agent; (2) frameshift-sensitive parent strains are more sensitive to the mutagenic effects of ionizing radiation than is the only strain studied that is sensitive to base-pair substitutions; and (3) enhancement of mutagenesis and survival is related to plasmid-mediated repair of DNA damage induced by ionizing radiation and does not involve damage induced by Cerenkov-generated uv radiation which is negligible for our irradiation conditions

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

    Science.gov (United States)

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

    2000-01-01

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

  15. A comprehensive survey of the mutagenic impact of common cancer cytotoxics

    DEFF Research Database (Denmark)

    Szikriszt, Bernadett; Poti, Adam; Pipek, Orsolya

    2016-01-01

    system, is well suited to accurately assay genomic mutations. Results: We use whole genome sequencing of multiple DT40 clones to determine the mutagenic effect of eight common cytotoxics used for the treatment of millions of patients worldwide. We determine the spontaneous mutagenesis rate at 2.3 x 10......-10 per base per cell division and find that cisplatin, cyclophosphamide and etoposide induce extra base substitutions with distinct spectra. After four cycles of exposure, cisplatin induces 0.8 mutations per Mb, equivalent to the median mutational burden in common leukaemias. Cisplatin-induced mutations......, hydroxyurea, doxorubicin and paclitaxel have no measurable mutagenic effect. The cisplatin-induced mutation spectrum shows good correlation with cancer mutation signatures attributed to smoking and other sources of guanine-directed base damage. Conclusion: This study provides support for the use of cell line...

  16. Mutagenic effects on indica rice carried by satellite

    International Nuclear Information System (INIS)

    Wu Dezhi; Liu Yongzhu; Guo Tao; Zhang Jianguo; Chen Zhiqiang; Wang Hui

    2010-01-01

    Dried seeds of four indica rice varieties were carried into space by satellite Shijia No.8, the mutagenic effects of space condition on the seeds vigor and agronomic traits in the SP 1 generation, and on the agronomic traits, amylose conent and bacterial resistance in the SP 2 generation were studied. The results showed that the space condition slightly damaged rice seeds, with the physiological damage rate of germination rate, bud length, plant height and seed-setting rate in the SP 1 ranged from 0 to 26.9%. Different varieties responded differently to the space conditions, and the order from strong to weak was Gui 99, Hanghui 7, R998, Jinhang 138. Compared with the control, no trait showed segregation in the SP 1 generation. Some traits appeared larger segregation in the SP 2 generation, and the mutants of plant height, number of tillers, weight of grain, amylose content and bacterial blight resistance were isolated in the SP 2 generation, and these mutation traits could be inherited the SP 3 generation. Space conditions not only produced mutants of rice agronomic traits, but also produced mutants of rice quality and disease resistance. (authors)

  17. The contribution to site core damage frequency from independent occurrences of initiators in two or more units: How low is it?

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong-San; Park, Jin Hee; Lim, Ho Gon [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2016-10-15

    Stutzke estimated the site risk by summing the contribution from common cause initiators and the contribution from single-unit initiators. He considered some kinds of multi-unit accident sequences caused by single-unit initiators. However, the contribution from independent occurrences of initiators in two or more units at a site was not taken into account. The purpose of this study is to estimate the contribution to site core damage frequency (CDF) from simultaneous occurrences of independent initiators in two or more units at the same site. Some assumptions and methods used in this analysis are firstly described, and the results and conclusions of the analysis are described. In this study, the contribution to site core damage frequency (CDF) from simultaneous occurrences of independent initiators in two or more units at the same site was estimated. A Korean six-unit site was selected as the reference site and the at-power internal events Level 1 PSA model for an OPR1000 unit at the reference site was used as the base model, and was modified to deal with some major dependencies between units at the site. Specifically, the availability of the AAC D/G, dependencies between offsite power recovery actions in different unis, and inter-unit CCF modeling for risk-significant components such as diesel generators were taken into account. As a result, the sum of dual-unit CDF due to independent occurrences of initiators in two units at the reference site was estimated to be sufficiently low to be neglected.

  18. Mutagenic activity of phthalate esters in bacterial liquid suspension assays.

    OpenAIRE

    Seed, J L

    1982-01-01

    The mutagenic activities of several phthalate esters have been evaluated in an 8-azaguanine resistance assay in Salmonella typhimurium. Three phthalate esters were found to be mutagenic: dimethyl phthalate, diethyl phthalate and di-n-butyl phthalate. A number of other phthalate esters were not found to be mutagenic, including di(2-ethylhexyl) phthalate, di-n-octyl phthalate, diallyl phthalate, diisobutyl phthalate and diisodecyl phthalate. A metabolite of di(2-ethylhexyl) phthalate, 2-ethylhe...

  19. Past, present, and future of mutagens in cooked foods.

    Science.gov (United States)

    Sugimura, T

    1986-08-01

    Mutation assay with Salmonella typhimurium enabled us to detect various types of mutagens in cooked foods. A series of mutagenic heterocyclic amines has been isolated and identified in broiled fish and meat and in pyrolyzates of amino acids and proteins. Feeding experiments showed these mutagens to be carcinogenic in mice and rats. The mechanism of formation and pathway of metabolic activation of these heterocyclic amines have been elucidated. Their contents in various cooked foods have been determined. The presence of mutagenic nitropyrenes (some of which were confirmed as carcinogens) in grilled chicken was also established. Roasted coffee beans also yield mutagens such as methylglyoxal. The formation of mutagen precursors, including beta-carboline derivatives and tyramine which become mutagens with nitrite treatment, was found during food processing. Oncogene activation in animal tumors induced by some of these food mutagens/carcinogens has been confirmed. The role of mutagens/carcinogens in cooked foods in human cancer development has not yet been exactly evaluated. In order to do this, more information on their carcinogenic potency, human intake, metabolism in the human body, and the effects of combined administration with other initiators, promoters and other modifying factors in food is required.

  20. Urinary 1-hydroxypyrene and mutagenicity in bus drivers and mail carriers exposed to urban air pollution in Denmark.

    Science.gov (United States)

    Hansen, Ase Marie; Wallin, Håkan; Binderup, Mona Lise; Dybdahl, Marianne; Autrup, Herman; Loft, Steffen; Knudsen, Lisbeth Ehlert

    2004-01-10

    Previous studies in Denmark have shown that bus drivers and tramway employees were at an increased risk for developing several types of cancer and that bus drives from central Copenhagen have high levels of biomarkers of DNA damage. The present study evaluates 1-hydroxypyrene concentrations and mutagenic activity in urine as biomarkers of exposure in non-smoking bus drivers in city and rural areas on a work day and a day off and in non-smoking mail carriers working outdoors (in the streets) and indoors (in the office). Twenty-four hour urine samples were collected on a working day and a day off from 60 non-smoking bus drivers in city and rural areas and from 88 non-smoking mail carriers working outdoors (in the streets) and indoors (in the office). The concentration of 1-hydroxypyrene was measured by means of HPLC and the mutagenic activity was assessed by the Ames assay with Salmonella tester strain YG1021 and S9 mix. The N-acetyltransferase (NAT2) phenotype was used as a biomarker for susceptibility to mutagenic/carcinogenic compounds. Bus drivers excreted more 1-hydroxypyrene in urine than did mail carriers. The differences were slightly smaller when NAT2 phenotype, cooking at home, exposure to vehicle exhaust, and performing physical exercise after work were included. The NAT2 slow acetylators had 29% (1.29 [CI: 1.15-1.98]) higher 1-hydroxypyrene concentrations in urine than the fast acetylators. Male bus drivers had 0.92 revertants/mol creatinine [CI: 0.37-1.47] and female bus drivers 1.90 revertants/mol creatinine [CI: 1.01-2.79] higher mutagenic activity in urine than mail carriers. The present study indicates that bus drivers are more exposed to polycyclic aromatic hydrocarbons (PAH) and mutagens than mail carriers. Mail carriers who worked outdoors had higher urinary concentration of 1-hydroxypyrene, a marker of exposure to PAH, than those working indoors. The individual levels of urinary mutagenic activity were not correlated to excretion of 1

  1. Estimated airborne release of plutonium from Westinghouse Cheswick site as a result of postulated damage from severe wind and seismic hazard

    International Nuclear Information System (INIS)

    Mishima, J.; Schwendiman, L.C.; Ayer, J.E.

    1979-06-01

    The potential airborne releases of plutonium (source terms) from postulated damage sustained by the Westinghouse Plutonium Fuel Development Laboratories at the Cheswick site in Pennsylvania as a result of various levels of wind and seismic hazard are estimated. The source terms are based on damage scenarios originated by other specialists and range up to 260 mph for wind hazard and in excess of 0.39 g ground acceleration for seismic hazard. The approaches and factors used to estimate the source terms (inventories of dispersible materials at risk, damage levels and ratios, fractional airborne releases of dispersible materials under stress, atmosphere exchange rates, and source term ranges) are discussed. Source term estimates range from less than 10 -7 g plutonium to greater than 130 g plutonium over a four-day period

  2. Mutagenicity testing of diethylene glycol monobutyl ether.

    Science.gov (United States)

    Thompson, E D; Coppinger, W J; Valencia, R; Iavicoli, J

    1984-01-01

    The mutagenic potential of diethylene glycol monobutyl ether (diEGBE) was examined with a Tier I battery of in vitro assays followed by a Tier II in vivo Drosophila sex-linked recessive lethal assay. The in vitro battery consisted of: the Salmonella mutagenicity test, the L5178Y mouse lymphoma test, a cytogenetics assay using Chinese hamster ovary cells and the unscheduled DNA synthesis (UDS) assay in rat hepatocytes. Results of the Salmonella mutagenicity test, the cytogenetics test, and the rat hepatocyte assay were negative at concentrations up to 20 microL/plate, 7.92 microL/mL, and 4.4 microL/mL, respectively. Toxicity was clearly demonstrated at all high doses. A weak, but dose-related increase in the mutation frequency (4-fold increase over the solvent control at 5.6 microL/mL with 12% survival) was obtained in the L5178Y lymphoma test in the absence of metabolic activation. Results of the mouse lymphoma assay were negative in the presence of the S-9 activation system. The significance of the mouse lymphoma assay were negative in the presence of the S-9 activation system. The significance of the mouse lymphoma assay results were assessed by performing the Tier II sex-linked recessive lethal assay in Drosophila in which the target tissue is maturing germinal cells. Both feeding (11,000 ppm for 3 days) and injection (0.3 microL of approximately 14,000 ppm solution) routes of administration were employed in the Drosophila assay. Approximately 11,000 individual crosses with an equal number of negative controls were performed for each route of administration. diEGBE produced no increase in recessive lethals under these conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6389113

  3. Cytotoxic, mutagenicity, and genotoxicity effects of guanylhydrazone derivatives.

    Science.gov (United States)

    Pinhatti, Valéria Rodrigues; da Silva, Juliana; Martins, Tales Leandro Costa; Moura, Dinara Jaqueline; Rosa, Renato Moreira; Villela, Izabel; Stopiglia, Cheila Denise Ottonelli; da Silva Santos, Selma; Scroferneker, Maria Lúcia; Machado, Carlos Renato; Saffi, Jenifer; Henriques, João Antonio Pêgas

    2016-08-01

    Several studies have reported that guanylhydrazones display a variety of desirable biological properties, such as antihypertensive, antibacterial, and antimalarial behaviour. They furthermore promote anti-pneumocystosis and anti-trypanosomiasis, exhibit antitumor activity, and show significant cytotoxicity against cancer cell lines. In this work, we have evaluated the cytotoxicity, mutagenicity, and genotoxicity of two guanylhydrazones derivatives, (E)-2-[(2,3-dimethoxyphenyl) methylene] hydrazine carboxymidamide hydrochloride (2,3-DMeB) and (E)-2-[(3,4-dimethoxyphenyl) methylene] hydrazine carboxymidamide hydrochloride (3,4-DMeB), in different biological models. Both 2,3-DMeB and 3,4-DMeB induce weak cytotoxic and mutagenic effects in bacteria and yeast. The genotoxicity of these compounds was determined in a fibroblast cell line (V79) using alkaline comet assay, as well as a modified comet assay with bacterial enzymes formamidopyrimidine DNA-glycosylase (FPG) and endonuclease III (EndoIII). Both guanylhydrazone derivatives induced DNA damage. Treatment of V79 cells with EndoIII and FPG proteins demonstrated a significant effect of 2,3-DMeB and 3,4-DMeB with respect to oxidized bases. In addition, the derivatives induced a significant increase in the frequency of micronucleated cells at high doses. The antifungal and anti-trypanosomal properties of these guanylhydrazone derivatives were also evaluated, and the obtained results suggest that 2,3-DMeB is more effective than 3,4-DMeB. The biological activity of 2,3-DMeB and 3,4-DMeB may thus be related, at least in part, to their oxidative potential, as well as to their ability to interact with DNA. Considering the previously reported in vitro antitumor activity of guanylhydrazone derivatives in combination with the lack of acute toxicity and the fact that DNA damage is only observed at high doses should render both compounds good candidates for in vivo studies on antitumor activity. Copyright © 2016 Elsevier B

  4. Analysis of commercial bouillons for trace levels of mutagens.

    Science.gov (United States)

    Stavric, B; Matula, T I; Klassen, R; Downie, R H

    1993-12-01

    A new method, developed specifically for the extraction of heterocyclic aromatic amine (HAA) type mutagens from different food matrices, was applied to various forms of commercially available bouillons. This procedure is based on liquid-liquid extraction of the sample at different pH values. Recovery and reproducibility of the procedure was determined by processing spiked samples using a mutagenicity bioassay technique as an endpoint. The mutagenicity was tested in the Salmonella/microsome assay using strain TA98 with metabolic activation. 22 bouillon samples in liquid, cube or powder forms from seven manufacturers were extracted and tested for potential mutagenicity. The mutagenic activity of these samples varied and ranged from non-detectable to about 1200 induced revertants per gram of solid material, with a median value of approximately 250 revertants/g. The mutagenic response appeared to be dependent on the source rather than the type or form of the product tested. A negative response was obtained from only one chicken bouillon, and the highest positive response was obtained from a beef bouillon in cube form. It appears that the average beef sample, regardless of form, has a higher mutagenic potency than chicken or chicken and turkey samples. Overall, the intake of mutagens from commercial bouillons (obtained as cubes, concentrates or dry mixes) to prepare one serving (as bouillon, soup, casseroles, etc.) is considerably less than that reported in the literature for one serving of fried beef or pork. The extractability and mutagenic characteristics of these samples indicate the presence of HAA-type mutagens. Work is in progress to identify the mutagenic factors in bouillons.

  5. Assessing chemical mutagens: the risk to humans

    International Nuclear Information System (INIS)

    Brewen, J.G.

    1978-01-01

    Some topics discussed are as follows: chromosomal aberrations induced by x radiation, tritiated thymidine, maleic hydrazide, and nitrogen mustard; removal of pyrimidine dimers by photoreactivation in amphibian cells following uv radiation; effects of 4-nitroquinoline-oxide on leukocytes from XP and normal patients; DNA as a target for alkylating agents; sensitivity of spermatogonia to chemical mutagens; chromosomal aberrations induced by 8-ethoxycaffeine, methoxycaffeine, cytosine arabinoside, streptonigrin, bleomycin, and phleomycin; effects of MMS and triethylenemelamine on germ cells; and use of chromosomal aberrations for improving risk estimates for ionizing radiation

  6. DNA damage, acetylcholinesterase activity and lysosomal stability in native and transplanted mussels (Mytilus edulis) in areas close to coastal chemical dumping sites in Denmark

    DEFF Research Database (Denmark)

    Rank, J.; Lehtonen, K. K.; Strand, J.

    2007-01-01

    of chemical pollution complex, as seen especially in the variability in results on DNA damage, and also in regard to AChE activity. These investigations further stress the importance of understanding the effects of natural factors (salinity, temperature, water levels, rain and storm events) in correct......Biomarkers of genotoxicity (DNA damage, measured as tail moment in the Comet assay), neurotoxicity (acetylcholinesterase inhibition, AChE) and general stress (lysosomal membrane stability, LMS) were studied in native and transplanted blue mussels (Mytilus edulis) in coastal areas of western Denmark...... potentially affected by anthropogenic pollution originating from chemical dumping sites. The results indicate responses to pollution in all the biomarkers applied at the suspected areas, but the results were not consistent. Seasonal fluctuations in exposure situations at the study sites make interpretation...

  7. Direct Binding to Replication Protein A (RPA)-coated Single-stranded DNA Allows Recruitment of the ATR Activator TopBP1 to Sites of DNA Damage*

    Science.gov (United States)

    Acevedo, Julyana; Yan, Shan; Michael, W. Matthew

    2016-01-01

    A critical event for the ability of cells to tolerate DNA damage and replication stress is activation of the ATR kinase. ATR activation is dependent on the BRCT (BRCA1 C terminus) repeat-containing protein TopBP1. Previous work has shown that recruitment of TopBP1 to sites of DNA damage and stalled replication forks is necessary for downstream events in ATR activation; however, the mechanism for this recruitment was not known. Here, we use protein binding assays and functional studies in Xenopus egg extracts to show that TopBP1 makes a direct interaction, via its BRCT2 domain, with RPA-coated single-stranded DNA. We identify a point mutant that abrogates this interaction and show that this mutant fails to accumulate at sites of DNA damage and that the mutant cannot activate ATR. These data thus supply a mechanism for how the critical ATR activator, TopBP1, senses DNA damage and stalled replication forks to initiate assembly of checkpoint signaling complexes. PMID:27129245

  8. FTIR analysis and evaluation of carcinogenic and mutagenic risks of nitro-polycyclic aromatic hydrocarbons in PM1.0.

    Science.gov (United States)

    Schneider, Ismael Luís; Teixeira, Elba Calesso; Agudelo-Castañeda, Dayana Milena; Silva E Silva, Gabriel; Balzaretti, Naira; Braga, Marcel Ferreira; Oliveira, Luís Felipe Silva

    2016-01-15

    Nitro-polycyclic aromatic hydrocarbons (NPAHs) represent a group of organic compounds of significant interest due to their presence in airborne particulates of urban centers, wide distribution in the environment, and mutagenic and carcinogenic properties. These compounds, associated with atmospheric particles of size PM1.0) using infrared spectrometry. Carcinogenic and mutagenic risks of the studied NPAHs associated with PM1.0 samples were also determined for two sampling sites: Canoas and Sapucaia do Sul. The results showed that NPAH standard spectra can effectively identify NPAHs in PM1.0 samples. The transmittance and emissivity sample spectra showed broader bands and lower relative intensity than the standard NPAH spectra. The carcinogenic risk and the total mutagenic risk were calculated using the toxic equivalent factors and mutagenic potency factors, respectively. Canoas showed the highest total carcinogenic risk, while Sapucaia do Sul had the highest mutagenic risk. The seasonal analysis suggested that in the study area the ambient air is more toxic during the cold periods. These findings might of significant importance for the decision and policy making authorities.

  9. Relationship between DNA replication and DNA repair in human lymphocytes proliferating in vitro in the presence and in absence of mutagen

    International Nuclear Information System (INIS)

    Szyfter, K.; Wielgosz, M.Sz.; Kujawski, M.; Jaloszynski, P.; Zajaczek, S.

    1995-01-01

    The effects of mutagens on DNA replication and DNA repair were studied in peripheral blood lymphocytes (PBL) obtained from 21 healthy subjects, 2 samples from healthy heterozygote of ''Xeroderma pigmentosum'' (XP) and 2 samples from patient with clinically recognised XP. Inter-individual variations were found in DNA replication and in the level of spontaneous DNA repair measured under standard culture condition. Exposure of human PBL proliferating in vitro to B(a)P was followed by a partial inhibition of replicative DNA synthesis in all subjects and by an induction of DNA repair in healthy subjects. In XP patients DNA repair synthesis remained at the level attributed to spontaneous DNA repair. The response to mutagen varied individually. Results were analysed statistically. It was established that the studied indices of DNA synthesis correlate well with each other. The highest correlation was found between the levels of spontaneous and B(a)P-induced DNA repair. It is concluded that the level of spontaneous DNA repair is predictive for an estimation of cells ability to repair DNA damage. Inter-individual variations in the inhibition of DNA replication and in DNA repair synthesis are also dependent on the type of mutagen as shown by effects of other mutagens. Different effects of mutagen exposure on the inhibition of DNA replicative synthesis and induction of DNA repair can be explained by genetically controlled differences in the activity of enzymes responsible for mutagen processing and lesion removal. (author). 37 refs, 2 figs, 2 tabs

  10. Studies on mutagenic effectiveness and efficiency in Fenugreek ...

    African Journals Online (AJOL)

    shagufta

    2013-05-01

    May 1, 2013 ... improvement, the basic studies on effectiveness and efficiency of a mutagen in a crop are necessary to recover high frequency of desirable mutations (Kumar and Mani, 1997; Badere and Chaudhary, 2007). Mutagenic effectiveness is an index of the response of a genotype to the increasing doses of the ...

  11. Is Tobacco Smoke a Germ-Cell Mutagen?

    Science.gov (United States)

    Although no international organization exists to declare whether an agent is a germ-cell mutagen, tobacco smoke may be a human germ-cell mutagen. In the mouse, tobacco smoke induces a significant increase in the mutation frequency at an expanded simple tandem repeat (ESTR) locus....

  12. Mutagenicity of quaternary ammonium salts containing carbohydrate moieties

    Energy Technology Data Exchange (ETDEWEB)

    Dmochowska, Barbara [Department of Carbohydrate Chemistry, University of Gdansk, Sobieskiego 18, 80-952 Gdansk (Poland); Piosik, Jacek; Woziwodzka, Anna [Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Kladki 24, 80-822 Gdansk (Poland); Sikora, Karol; Wisniewski, Andrzej [Department of Carbohydrate Chemistry, University of Gdansk, Sobieskiego 18, 80-952 Gdansk (Poland); Wegrzyn, Grzegorz, E-mail: wegrzyn@biotech.univ.gda.pl [Department of Molecular Biology, University of Gdansk, Kladki 24, 80-822 Gdansk (Poland)

    2011-10-15

    Highlights: {yields} A series of quaternary ammonium salts containing carbohydrate moieties, with configuration D-galacto, D-gluco and D-manno, was synthesized and characterized. {yields} The quaternary ammonium salts containing carbohydrate moieties revealed potent mutagenic activities, as assessed by using the Vibrio harveyi bioluminescence mutagenicity test. {yields} The N-[2-(D-glycopyranosyloxy)ethyl]-N,N,N-trimethylaminium salts were of the highest activity in the mutagenicity assay. {yields} We suggest that quaternary ammonium salts may be more hazardous than previously supposed. - Abstract: Quaternary ammonium salts are widely used in industrial, agricultural, healthcare and domestic applications. They are believed to be safe compounds, with little or no health hazard to humans. However, in this report, we demonstrate that a series of newly synthesized quaternary ammonium salts containing carbohydrate moieties reveal potent mutagenic activities, as assessed by using the Vibrio harveyi bioluminescence mutagenicity test. D-Gluco- and D-galacto-derivatives were found to have a higher mutagenic potential than D-manno-derivatives. Among the former groups of compounds, the N-[2-(D-glycopyranosyloxy)ethyl]-N,N,N-trimethylaminium salts were of the highest activity in the mutagenicity assay. These results suggest that the safety of quaternary ammonium salts may be lower than previously supposed, indicating a need for testing such compounds for their mutagenicity.

  13. QSAR ligand dataset for modelling mutagenicity, genotoxicity, and rodent carcinogenicity

    Directory of Open Access Journals (Sweden)

    Davy Guan

    2018-04-01

    Full Text Available Five datasets were constructed from ligand and bioassay result data from the literature. These datasets include bioassay results from the Ames mutagenicity assay, Greenscreen GADD-45a-GFP assay, Syrian Hamster Embryo (SHE assay, and 2 year rat carcinogenicity assay results. These datasets provide information about chemical mutagenicity, genotoxicity and carcinogenicity.

  14. Mutagenicity of quaternary ammonium salts containing carbohydrate moieties

    International Nuclear Information System (INIS)

    Dmochowska, Barbara; Piosik, Jacek; Woziwodzka, Anna; Sikora, Karol; Wisniewski, Andrzej; Wegrzyn, Grzegorz

    2011-01-01

    Highlights: → A series of quaternary ammonium salts containing carbohydrate moieties, with configuration D-galacto, D-gluco and D-manno, was synthesized and characterized. → The quaternary ammonium salts containing carbohydrate moieties revealed potent mutagenic activities, as assessed by using the Vibrio harveyi bioluminescence mutagenicity test. → The N-[2-(D-glycopyranosyloxy)ethyl]-N,N,N-trimethylaminium salts were of the highest activity in the mutagenicity assay. → We suggest that quaternary ammonium salts may be more hazardous than previously supposed. - Abstract: Quaternary ammonium salts are widely used in industrial, agricultural, healthcare and domestic applications. They are believed to be safe compounds, with little or no health hazard to humans. However, in this report, we demonstrate that a series of newly synthesized quaternary ammonium salts containing carbohydrate moieties reveal potent mutagenic activities, as assessed by using the Vibrio harveyi bioluminescence mutagenicity test. D-Gluco- and D-galacto-derivatives were found to have a higher mutagenic potential than D-manno-derivatives. Among the former groups of compounds, the N-[2-(D-glycopyranosyloxy)ethyl]-N,N,N-trimethylaminium salts were of the highest activity in the mutagenicity assay. These results suggest that the safety of quaternary ammonium salts may be lower than previously supposed, indicating a need for testing such compounds for their mutagenicity.

  15. Changes in mutagenicity of protein pyrolyzates by reaction with nitrite.

    Science.gov (United States)

    Yoshida, D; Matsumoto, T

    1978-09-01

    Pyrolyzates of protein and related materials were treated with nitrite under acidic conditions, and the mutagenic activity toward Salmonella tester strains was determined. After treatment with nitrite in acidic solution, casein pyrolyzate, an extract of roasted chicken meat, tobacco-smoke condensate and some aromatic amines showed appreciable decreases in their mutagenic activities toward Salmonella typhimurium TA 98. Aromatic amines in the pyrolyzates may be changed by nitrite treatment to other forms having no or lower mutagenic activity toward Salmonella typhimurium TA 98. The contribution by aromatic amines to the total mutagenic activity of the pyrolyzates was as high as 80% in both casein pyrolyzate and extract of roasted chicken meat and 50% in tobacco-smoke condensate. Pyrolyzates of protein and related materials did not show a decrease in the mutagenic activity toward Salmonella typhimurium TA 100 with the same treatment.

  16. Lead induces DNA damage and alteration of ALAD and antioxidant genes mRNA expression in construction site workers.

    Science.gov (United States)

    Akram, Zertashia; Riaz, Sadaf; Kayani, Mahmood Akhtar; Jahan, Sarwat; Ahmad, Malik Waqar; Ullah, Muhammad Abaid; Wazir, Hizbullah; Mahjabeen, Ishrat

    2018-01-16

    Oxidative stress and DNA damage are considered as possible mechanisms involved in lead toxicity. To test this hypothesis, DNA damage and expression variations of aminolevulinic acid dehydratase (ALAD), superoxide dismutase 2 (SOD2), and 8-oxoguanine DNA glycosylase 2a (OGG1-2a) genes was studied in a cohort of 100 exposed workers and 100 controls with comet assay and real-time polymerse chain reaction (PCR). Results indicated that increased number of comets was observed in exposed workers versus controls (p gene.

  17. Mutagenicity screening: General principles and minimal criteria. Report of a committee of the European Environmental Mutagen Society

    NARCIS (Netherlands)

    Kilbey, B.J.; Igali, S.; Lohman, P.H.M.

    1978-01-01

    A statement of general principles and minimal criteria for the screening of chemicals for potential mutagenicity in man that may be used as guidelines for regulatory agencies and industrial organisations. To make clear the potentialities and current limitations of short-term mutagenicity testing for

  18. The relative cytotoxicity and mutagenicity of cyclobutane pyrimidine dimers and photoproducts in Escherichia coli cells

    International Nuclear Information System (INIS)

    Tang, Moon-shong; Hrncir, J.; Mitchell, D.; Ross, J.; Clarkson, J.

    1986-01-01

    In order to calculate the relative cytotoxicity and mutagenicity of cyclobutane pyrimidine dimers and photoproducts, the authors have measured survival and mutation induction in UV-irradiated excision-deficient E. coli uvrA cells, with or without complete photoreactivation of the dimers. Radioimmunoassays with specificity for dimers or photoproducts have shown that maximum photoreactivation eliminates all of the dimers produce up to 10 Jm -2 254-nm light, while it has no effect on photoproducts. These results were confirmed by measuring the frequency of T4 endonuclease V-sensitive sites. Based on the best fit equations for survival and mutation induction, the authors have found that the calculated cytotoxicity of photoproducts is similar to that of dimers; however, the former is much more mutagenic than the latter. (Auth.)

  19. Pharmaceutical wastewater being composite mixture of environmental pollutants may be associated with mutagenicity and genotoxicity.

    Science.gov (United States)

    Sharif, Ali; Ashraf, Muhammad; Anjum, Aftab Ahmed; Javeed, Aqeel; Altaf, Imran; Akhtar, Muhammad Furqan; Abbas, Mateen; Akhtar, Bushra; Saleem, Ammara

    2016-02-01

    Pharmaceutical industries are amongst the foremost contributor to industrial waste. Ecological well-being is endangered owing to its facile discharge. In the present study, heavy metals and organic contaminants in waste water were characterized using atomic absorption spectrophotometer and GC-MS, respectively. Mutagenicity and genotoxic potential of pharmaceutical waste water were investigated through bacterial reverse mutation assay and in vitro comet assay, respectively. Ames test and comet assay of first sample were carried out at concentrations of 100, 50, 25, 12.5, 6.25 % v/v effluent with distilled water. Chromium (Cr), lead (Pb), arsenic (As), and cadmium (Cd) were found in high concentrations as compared to WHO- and EPA-recommended maximum limits. Arsenic was found to be the most abundant metal and its maximum concentration was 0.8 mg.L(-1). GC-MS revealed the presence of lignocaine, digitoxin, trimethoprim, caffeine, and vitamin E in waste water. Dose-dependent decrease in mutagenic index was observed in both strains. Substantial increase in mutagenicity was observed for TA-100, when assay was done by incorporating an enzyme activation system, whereas a slight increase was detected for TA-102. In vitro comet assay of waste water exhibited decrease in damage index and percentage fragmentation with the increase in dilution of waste water. Tail length also decreased with an increase in the dilution factor of waste water. These findings suggest that pharmaceutical waste water being a mix of different heavy metals and organic contaminants may have a potent mutagenic and genotoxic effect on exposed living organisms.

  20. Practical aspects of mutagenicity testing strategy: an industrial perspective.

    Science.gov (United States)

    Gollapudi, B B; Krishna, G

    2000-11-20

    Genetic toxicology studies play a central role in the development and marketing of new chemicals for pharmaceutical, agricultural, industrial, and consumer use. During the discovery phase of product development, rapid screening tests that require minimal amounts of test materials are used to assist in the design and prioritization of new molecules. At this stage, a modified Salmonella reverse mutation assay and an in vitro micronucleus test with mammalian cell culture are frequently used for screening. Regulatory genetic toxicology studies are conducted with a short list of compounds using protocols that conform to various international guidelines. A set of four assays usually constitutes the minimum test battery that satisfies global requirements. This set includes a bacterial reverse mutation assay, an in vitro cytogenetic test with mammalian cell culture, an in vitro gene mutation assay in mammalian cell cultures, and an in vivo rodent bone marrow micronucleus test. Supplementary studies are conducted in certain instances either as a follow-up to the findings from this initial testing battery and/or to satisfy a regulatory requirement. Currently available genetic toxicology assays have helped the scientific and industrial community over the past several decades in evaluating the mutagenic potential of chemical agents. The emerging field of toxicogenomics has the potential to redefine our ability to study the response of cells to genetic damage and hence our ability to study threshold phenomenon.

  1. Brief communication: On-site data collection of damage caused by flash floods: Experiences from Braunsbach, Germany, in May/June 2016

    Science.gov (United States)

    Laudan, Jonas; Rözer, Viktor; Sieg, Tobias; Vogel, Kristin; Thieken, Annegret

    2017-04-01

    At the end of May and beginning of June 2016, several municipalities in Southern Germany suffered from severe flash floods and debris flows which have been triggered by intense rainfall in Central Europe. Overall, the insured losses of these events amounted to EUR 1.2 billion in Germany. Especially the strong and unexpected flash flood on May 29th in Braunsbach (Baden Wurttemberg) - a small village counting about 1,000 residents - attracted media and policymakers due to its devastating character. The understanding of damage caused by flash floods requires ex-post collection of relevant but yet sparsely available information, linking process intensities to damage by using adequate methods of data gathering. Thus, on-site data collection was carried out after the flash flood event in Braunsbach, using open source software as helpful and efficient tool for data acquisition and evaluation. A digital survey was designed and conducted by a team of five researchers who investigated all buildings affected by water and debris flows. The collected data includes an estimation of a particular damage class, the inundation depth, and other relevant information. A post - hoc data analysis was done with R 3.3.1 and QGIS 2.14.3, performing both, a Random Forest Model (RF) and Random Generalized Linear Model (RGLM) as well as preparing a Spearman's rank correlation matrix. For visual interpretation and better overview of the study area and analysis results, a "process intensity" map was created, revealing important links of damage driving factors. We find that not only the water depth, which is often considered as only damage driving factor in riverine flood loss modelling, but also the exposition of a building to the flow direction and susceptible building parts like e.g. shop windows seem to be risk factors in flash-flood prone regions. Although no significant correlations were found, the analyses indicate that also building material (i.e. half-timbered or masonry) and structural

  2. Repair in unicellular green algae under the chronic action of mutagenic factors

    International Nuclear Information System (INIS)

    Sergeeva, S.A.; Ptitsina, S.N.; Shevchenko, V.A.

    1986-01-01

    Repair of single-standed DNA breaks in different strains of unicellular green Chlamidomonas reinhardii algae under the chronic action of mutagenic factors after γ-radiation was studied. It is shown, that the highest DNA break repair efficiency is observed in M γ mt++ strain, resistant to radiation. Strains, sensitive to UV-rays, possess the same repair efficiency as a wild type strain. UVS-1 strain demonstrated a higher repair efficiency, than a wild type strain. All that gives evidence of the difference in Chlamidomonas reinhardii of repair ways, leading to repair of damages, induced by γ-radiation and UV-rays

  3. [Evaluation of the mutagenicity of detergents by tests on bacteria, plant cells and human leucocytes.].

    Science.gov (United States)

    Feretti, Donatella; Pedrazzani, Roberta; Ceretti, Elisabetta; Zerbini, Ilaria; Gozio, Eleonora; Belotti, Caterina; Alias, Carlotta; Donato, Francesco; Gelatti, Umberto

    2009-01-01

    The aim of this study was to evaluate the mutagenicity of several traditional detergents and that of newer more biodegradable detergents, by using a bacterial test (Ames test), a plant cell test (Allium cepa micronuclei test) and a human leucocyte test (Comet test). All tests were conducted using a wide range of doses (1-2000 mg/l). None of the examined detergents induced mutations in S.typhimurium. One traditional detergent showed a genotoxic effect with the A. cepa test, while all newer detergents and one traditional detergent were shown by the Comet test to be capable of inducing DNA damage.

  4. Recent perspectives on the relations between faecal mutagenicity, genotoxicity and diet

    Directory of Open Access Journals (Sweden)

    Silvia eGratz

    2011-03-01

    Full Text Available DNA damage is an essential component of the genesis of colonic cancer. Gut microbial products and food components are thought to be principally responsible for the damage that initiates disease progression. Modified Ames tests and Comet assays have been developed for measuring mutagenicity and genotoxicity. Their relevance to oncogenesis remains to be confirmed, as does the relative importance of different mutagenic and genotoxic compounds present in faecal water and the bacteria involved in their metabolism. Dietary intervention studies provide clues to the likely risks of oncogenesis. High-protein diets lead to increases in N-nitroso compounds in faecal water and greater DNA damage as measured by the Comet assay, for example. Other dietary interventions, such as non-digestible carbohydrates and probiotics, may lead to lower faecal genotoxicity. In order to make recommendations to the general public, we must develop a better understanding of how genotoxic compounds are formed in the colon, how accurate the Ames and Comet assays are, and how diet affects genotoxicity.

  5. Mitotic catastrophe is the mechanism of lethality for mutations that confer mutagen sensitivity in Aspergillus nidulans.

    Science.gov (United States)

    Denison, S H; May, G S

    1994-01-16

    We have examined the consequences of treatment with DNA-damaging agents of uvs mutants and the bimD6 mutant of Aspergillus nidulans. We first established that wild-type Aspergillus undergoes a cell cycle delay following treatment with the DNA-damaging agents methyl methanesulfonate (MMS) or ultraviolet light (UV). We have also determined that strains carrying the bimD6, uvsB110, uvsH77, uvsF201 and the uvsC114 mutations, all of which cause an increased sensitivity to DNA-damaging agents, undergo a cell-cycle delay following DNA damage. These mutations therefore do not represent nonfunctional checkpoints in Aspergillus. However, all of the mutant strains accumulated nuclear defects after a period of delay following mutagen treatment. The nuclear defects in the uvsB110 and bimD6 strains following MMS treatment were shown to be dependent on passage through mitosis after DNA damage, as the defects were prevented with benomyl. Checkpoint controls responding to DNA damage thus only temporarily halt cell-cycle progression in response to DNA damage. The conditional bimD6 mutation also results in a defective mitosis at restrictive temperatures. This mitotic defect is similar to that seen with MMS treatment at temperatures permissive for the mitotic defect. Thus the bimD gene product may perform dual roles, one in DNA repair and the other during the mitotic cell cycle in the absence of damage.

  6. Assessment of DNA Damage by RAPD in Paracentrotus lividus Embryos Exposed to Amniotic Fluid from Residents Living Close to Waste Landfill Sites

    Directory of Open Access Journals (Sweden)

    Maurizio Guida

    2010-01-01

    Full Text Available The aim of this study was to assess the genotoxic effects of environmental chemicals on residents living near landfills. The study was based on samples of amniotic fluid from women living in the intensely polluted areas around the Campania region of Italy compared to a nonexposed control group. We evaluated the genetic effects that this amniotic fluids collected in contaminated sites had on Paracentrotus lividus embryos. DNA damage was detected through changes in RAPD (Random Amplified Polymorphism DNA profiles. The absence of the amplified DNA fragments indicated deletions in Paracentrotus lividus DNA exposed to the contaminated amniotic fluids when compared to equal exposure to uncontaminated fluids. These results show the ability of RAPD-PCR to detect and isolate DNA sequences representing genetic alterations induced in P. lividus embryos. Using this method, we identified two candidate target regions for DNA alterations in the genome of P. lividus. Our research indicates that RAPD-PCR in P. lividus embryo DNA can provide a molecular approach for studying DNA damage from pollutants that can impact human health. To our knowledge, this is the first time that assessment of DNA damage in P. lividus embryos has been tested using the RAPD strategy after exposure to amniotic fluid from residents near waste landfill sites.

  7. Comparing the use of 4.6 um lasers versus 10.6 um lasers for mitigating damage site growth on fused silica surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Yang, S T; Matthews, M J; Elhadj, S; Cooke, D; Guss, G M; Draggoo, V G; Wegner, P J

    2010-10-21

    The advantage of using mid-infrared (IR) 4.6 {micro}m lasers, versus far-infrared 10.6 {micro}m lasers, for mitigating damage growth on fused silica is investigated. In contrast to fused silica's high absorption at 10.6 {micro}m, silica absorption at 4.6 {micro}m is two orders of magnitude less. The much reduced absorption at 4.6 {micro}m enables deep heat penetration into fused silica when it is heated using the mid-IR laser, which in turn leads to more effective mitigation of damage sites with deep cracks. The advantage of using mid-IR versus far-IR laser for damage growth mitigation under non-evaporative condition is quantified by defining a figure of merit (FOM) that relates the crack healing depth to laser power required. Based on our FOM, we show that for damage cracks up to at least 500 {micro}m in depth, mitigation using a 4.6 {micro}m mid-IR laser is more efficient than mitigation using a 10.6 {micro}m far-IR laser.

  8. Damages to DNA that result in neoplastic transformation

    International Nuclear Information System (INIS)

    Setlow, R.B.

    1975-01-01

    Some topics discussed are: correlation between carcinogens and mutagens; defective DNA repair in uv-damaged xeroderma pigmentosum cells; analysis of nucleotide damage to DNA following exposure to chemicals or radiations; photoreactivation in uv-irradiated Escherichia coli; tumor development in fish; excision repair as an aid in identifying damage; detection of excision repair; role of endonucleases in repair of uv damage; and alkylation products and tumors

  9. Mutagenic effects of ion implantation on stevia

    International Nuclear Information System (INIS)

    Wang Cailian; Shen Mei; Chen Qiufang; Lu Ting; Shu Shizhen

    1998-01-01

    Dry seeds of Stevia were implanted by 75 keV nitrogen and carbon ions with various doses. The biological effects in M 1 and mutation in M 2 were studied. The results showed that ion beam was able to induce variation on chromosome structure in root tip cells. The rate of cells with chromosome aberration was increased with ion beam dose. The rate of cells with chromosomal aberration was lower than that induced with γ-rays. Frequency of the mutation induced by implantation of N + and C + ions were higher than those induced by γ-rays. The rate of cell with chromosome aberration and in M 2 useful mutation induced by implantation of C + ion was higher than those induced by implantation of N + ion. Mutagenic effects Feng 1 x Riyuan and Riyuan x Feng 2 by implantation of N + and C + were higher than that of Jining and Feng 2

  10. Core damage vulnerability due to the loss of ESW [essential service water] systems at multiplant sites: An assessment and options

    International Nuclear Information System (INIS)

    Kohut, P.; Musicki, Z.; Fitzpatrick, R.

    1989-01-01

    The main objective of this study is to establish the core damage vulnerability caused by the failure of the ESW systems in multiplant units that have only two sw pumps per unit with crosstie capability. Design and operating data have been surveyed to derive system failure frequency. A core damage model is constructed including operating configurations, specific recovery actions, and time and leak rate dependent RCP seal LOCA model. The estimated CDF SW = 2.55 x 10 -4 /yr is significant indicating the potential vulnerability of this particular SW design arrangement. A number of different potential improvements have been considered. The addition of a swing pump serving both units is shown to have the most significant CDF reduction potential (∼50%) combined with advantageous cost/benefit aspects. 2 refs., 2 tabs

  11. Metabolic aspects of pyrolysis mutagens in food

    International Nuclear Information System (INIS)

    Sato, S.; Negishi, C.; Umemoto, A.; Sugimura, T.

    1986-01-01

    The first step in metabolic activation of mutagenic and carcinogenic heterocyclic amines has been elucidated to be N-hydroxylation by cytochrome P-448. N-Hydroxyamino compounds are further activated to form N-O-acyl derivatives that readily react with DNA. The adducts between the metabolites of Trp-P-2 and Glu-P-1 and DNA were shown to have a C 8 -guanylamino structure. In the case of Glu-P-1, modification of guanine in GC clusters occurred preferentially. Glutathione transferases and myeloperoxidase were shown to inactivate some heterocyclic amines or their active metabolites. Hemin and fatty acids bind to and inactivate them. Fibers and other factors from vegetables also work to inactivate heterocyclic amines. Nitrite at low pH also degraded some heterocyclic amines, but those with an imidazole moiety were resistant. Glu-P-1 induced intestinal tumors in a high incidence when fed orally to rats. When 14 C-Glu-P-1 was administered by gavage into rats about 50% and 35% were excreted into feces and urine, respectively, within 24 hr. When the bile was collected, around 60% of radioactivity was excreted into it within 24 hr. In the bile, N-acetyl-Glu-P-1 was identified as one of the metabolites of Glu-P-1. It showed a mutagenic activity of about one fourth that of Glu-P-1 with S9 mix. Some radioactivity was also detected in the blood. At 24 hr after administration, most of the radioactivity was found to be bound to erythrocyte β-globins and serum proteins including albumin

  12. Multi-site damage localization in anisotropic plate-like structures using an active guided wave structural health monitoring system

    International Nuclear Information System (INIS)

    Moll, J; Schulte, R T; Fritzen, C-P; Hartmann, B; Nelles, O

    2010-01-01

    A new approach for structural health monitoring using guided waves in plate-like structures has been developed. In contrast to previous approaches, which mainly focused on isotropic or quasi-isotropic plates, the proposed algorithm does not assume any simplifications regarding anisotropic wave propagation. Thus, it can be used to improve the probability of detection. In this paper the mathematical background for damage localization in anisotropic plates will be introduced. This is an extension of the widely known ellipse method. The formalism is based on a distributed sensor network, where each piezoelectric sensor acts in turn as an actuator. The automatic extraction of the onset time of the first waveform in the differential signal in combination with a statistical post-processing via a two-dimensional probability density function and the application of the expectation-maximization algorithm allows a completely automatic localization procedure. Thus, multiple damages can be identified at the same time. The present study uses ultrasonic signals provided by the spectral element method. This simulation approach shows good agreement with experimental measurements. A local linear neural network is used to model the nonlinear dispersion curves. The benefit of using a neural network approach is to increase the angular resolution that results from the sparse sensor network. Furthermore, it can be used to shorten the computational time for the damage localization procedure

  13. Mutagenicity of anthraquinone and hydroxylated anthraquinones in the Ames/Salmonella microsome system.

    Science.gov (United States)

    Liberman, D F; Fink, R C; Schaefer, F L; Mulcahy, R J; Stark, A A

    1982-01-01

    The mutagenicity of anthracene, anthraquinone, and four structurally similar compounds of each was evaluated in the Ames/Salmonella microsome assay. Anthraquinone was shown to be mutagenic for strains TA1537, TA1538, and TA98 in the absence of rat liver homogenate. The four anthraquinone derivatives tested were mutagenic for TA1537 exclusively. None of the anthracenes exhibited mutagenic activity. PMID:7103489

  14. Mutagenicity of anthraquinone and hydroxylated anthraquinones in the Ames/Salmonella microsome system.

    OpenAIRE

    Liberman, D F; Fink, R C; Schaefer, F L; Mulcahy, R J; Stark, A A

    1982-01-01

    The mutagenicity of anthracene, anthraquinone, and four structurally similar compounds of each was evaluated in the Ames/Salmonella microsome assay. Anthraquinone was shown to be mutagenic for strains TA1537, TA1538, and TA98 in the absence of rat liver homogenate. The four anthraquinone derivatives tested were mutagenic for TA1537 exclusively. None of the anthracenes exhibited mutagenic activity.

  15. Site specific X-ray induced changes in organic and metal organic compounds and their influence on global radiation damage

    International Nuclear Information System (INIS)

    Heintz, Desiree Ellen

    2012-07-01

    The aim of this work was to systematically investigate the effects of specific and global X-ray radiation damage to biological samples and obtain a conclusive model to describe the underlying principles. Based on the systematic studies performed in this work, it was possible to propose two conclusive mechanisms to describe X-ray induced photoreduction and global radiation damage. The influence of chemical composition, temperature and solvent on X-ray induced photoreduction was investigated by X-ray Absorption Near Edge Spectroscopy and single crystal X-ray diffraction of two B12 cofactors - cyano- and methylcobalamin - as well as iron(II) and iron(III) complexes. The obtained results revealed that X-ray induced photoreduction is a ligand dependent process, with a redox reaction taking place within the complex. It could further be shown that selective hydrogen abstraction plays an important role in the process of X-ray induced photoreduction. Based on the experimental results of this work, a model to describe X-ray induced photoreduction of metal organic complexes could be proposed. The process of X-ray induced hydrogen abstraction was further investigated in a combined X-ray and neutron diffraction study on the amino acids L-serine and L-alanine, which were used as model compounds for proteins, and the nucleoside deoxythymidine (thymidine) as a model for DNA. A damage mechanism for L-serine could be found. It involves the abstraction of two hydrogen atoms, one from the hydroxyl group and one from the adjacent methylene group. Such a hydrogen abstraction results in the formation of a carbonyl group. X-ray diffraction measurements on cyano- and methylcobalamin as well as on three metal amino acid complexes, containing nickel(II) and copper(II), respectively, were conducted to investigate the contribution of X-ray induced photoreduction to global radiation damage. Results from these measurements combined with the results from L-serine, L-alanine and thymidine allowed

  16. Site specific X-ray induced changes in organic and metal organic compounds and their influence on global radiation damage

    Energy Technology Data Exchange (ETDEWEB)

    Heintz, Desiree Ellen

    2012-07-15

    The aim of this work was to systematically investigate the effects of specific and global X-ray radiation damage to biological samples and obtain a conclusive model to describe the underlying principles. Based on the systematic studies performed in this work, it was possible to propose two conclusive mechanisms to describe X-ray induced photoreduction and global radiation damage. The influence of chemical composition, temperature and solvent on X-ray induced photoreduction was investigated by X-ray Absorption Near Edge Spectroscopy and single crystal X-ray diffraction of two B12 cofactors - cyano- and methylcobalamin - as well as iron(II) and iron(III) complexes. The obtained results revealed that X-ray induced photoreduction is a ligand dependent process, with a redox reaction taking place within the complex. It could further be shown that selective hydrogen abstraction plays an important role in the process of X-ray induced photoreduction. Based on the experimental results of this work, a model to describe X-ray induced photoreduction of metal organic complexes could be proposed. The process of X-ray induced hydrogen abstraction was further investigated in a combined X-ray and neutron diffraction study on the amino acids L-serine and L-alanine, which were used as model compounds for proteins, and the nucleoside deoxythymidine (thymidine) as a model for DNA. A damage mechanism for L-serine could be found. It involves the abstraction of two hydrogen atoms, one from the hydroxyl group and one from the adjacent methylene group. Such a hydrogen abstraction results in the formation of a carbonyl group. X-ray diffraction measurements on cyano- and methylcobalamin as well as on three metal amino acid complexes, containing nickel(II) and copper(II), respectively, were conducted to investigate the contribution of X-ray induced photoreduction to global radiation damage. Results from these measurements combined with the results from L-serine, L-alanine and thymidine allowed

  17. [Smoked sausages and food additives: evaluation of total mutagenic activity].

    Science.gov (United States)

    Dugan, A M; Tkacheva, D L

    2011-01-01

    The paper deals with the evaluation of the total mutagenic activity of samples of the inorganic and organic fractions of three technology smoked sausages (boiled-smoked, semi-smoked, and raw-smoked) and some food additives used to manufacture the above sausages. Their mild and moderate mutagenic effects were recorded in a Salmonella typhimurium bacterial test system with a metabolic activation system. Physicochemical analysis of the fractions of the smoked sausages has shown that their study samples are substantially contaminated with heavy metals and representatives of polycyclic aromatic hydrocarbons, partially causing the mutagenic effects observed.

  18. Mutagenicity in drug development: interpretation and significance of test results.

    Science.gov (United States)

    Clive, D

    1985-03-01

    The use of mutagenicity data has been proposed and widely accepted as a relatively fast and inexpensive means of predicting long-term risk to man (i.e., cancer in somatic cells, heritable mutations in germ cells). This view is based on the universal nature of the genetic material, the somatic mutation model of carcinogenesis, and a number of studies showing correlations between mutagenicity and carcinogenicity. An uncritical acceptance of this approach by some regulatory and industrial concerns is over-conservative, naive, and scientifically unjustifiable on a number of grounds: Human cancers are largely life-style related (e.g., cigarettes, diet, tanning). Mutagens (both natural and man-made) are far more prevalent in the environment than was originally assumed (e.g., the natural bases and nucleosides, protein pyrolysates, fluorescent lights, typewriter ribbon, red wine, diesel fuel exhausts, viruses, our own leukocytes). "False-positive" (relative to carcinogenicity) and "false-negative" mutagenicity results occur, often with rational explanations (e.g., high threshold, inappropriate metabolism, inadequate genetic endpoint), and thereby confound any straightforward interpretation of mutagenicity test results. Test battery composition affects both the proper identification of mutagens and, in many instances, the ability to make preliminary risk assessments. In vitro mutagenicity assays ignore whole animal protective mechanisms, may provide unphysiological metabolism, and may be either too sensitive (e.g., testing at orders-of-magnitude higher doses than can be ingested) or not sensitive enough (e.g., short-term treatments inadequately model chronic exposure in bioassay). Bacterial systems, particularly the Ames assay, cannot in principle detect chromosomal events which are involved in both carcinogenesis and germ line mutations in man. Some compounds induce only chromosomal events and little or no detectable single-gene events (e.g., acyclovir, caffeine

  19. Mutagenic effectiveness and efficiency of gamma rays and ethyl methanesulhonate in Indian mustard

    International Nuclear Information System (INIS)

    Prasad, Rajendra; Singh, Basudeo

    1986-01-01

    Mutagenic effectiveness is a measure of the frequency of mutations induced by unit dose of a mutagen while mutagenic efficiency gives the proportion of mutations in relation to other associated undesirable biological effects such as gross chromosomal aberrations, lethality and sterility induced by the mutagen in question (Konzak, et al., 1965). The usefulness of any mutagen in plant breeding depends not only on its mutagenic effectiveness but also on its mutagenic efficiency. The efficiency and effectiveness of ethyl methanesulphonate (EMS) in relation to gamma rays in Indian mustard [Brassica juncea (L.) Czern and Coss] was studied. (author)

  20. Efficacy of plastic mesh tubes in reducing herbivory damage by the invasive nutria (Myocastor coypus) in an urban restoration site

    Science.gov (United States)

    Sheffels, Trevor R.; Systma, Mark D.; Carter, Jacoby; Taylor, Jimmy D.

    2014-01-01

    The restoration of stream corridors is becoming an increasingly important component of urban landscape planning, and the high cost of these projects necessitates the need to understand and address potential ecological obstacles to project success. The nutria(Myocastor coypus) is an invasive, semi-aquatic rodent native to South America that causes detrimental ecological impacts in riparian and wetland habitats throughout its introduced range, and techniques are needed to reduce nutria herbivory damage to urban stream restoration projects. We assessed the efficacy of standard Vexar® plastic mesh tubes in reducing nutria herbivory damage to newly established woody plants. The study was conducted in winter-spring 2009 at Delta Ponds, a 60-ha urban waterway in Eugene, Oregon. Woody plants protected by Vexar® tubes demonstrated 100% survival over the 3-month initial establishment period, while only 17% of unprotected plantings survived. Nutria demonstrated a preference for black cottonwood (Populus balsamifera ssp trichocarpa) over red osier dogwood (Cornussericea) and willow (Salix spp). Camera surveillance showed that nutria were more active in unprotected rather than protected treatments. Our results suggest that Vexar® plastic mesh tubing can be an effective short-term herbivory mitigation tool when habitat use by nutria is low. Additionally, planting functionally equivalent woody plant species that are less preferred by nutria, and other herbivores, may be another method for reducing herbivory and improving revegetation success. This study highlights the need to address potential wildlife damage conflicts in the planning process for stream restoration in urban landscapes.

  1. Damage estimates for European and U.S.sites using the U.S. high-cycle fatigue data base

    Energy Technology Data Exchange (ETDEWEB)

    Sutherland, H J [Wind Energy Technology, Sandia National Lab., Albuquerque, NM (United States)

    1996-09-01

    This paper uses two high-cycle fatigue data bases, one for typical U.S. blade materials and one for European materials, to analyze the service lifetime of a wind turbine blade subjected to the WISPER load spectrum for northern European sites and the WISPER protocol load spectrum for U.S. wind farm sites. The U.S. data base contains over 2200 data points that were obtained using coupon testing procedures. These data are used to construct a Goodman diagram that is suitable for analyzing wind turbine blades. This result is compared to the Goodman diagram derived from the European fatigue data base FACT. The LIFE2 fatigue analysis code for wind turbines is then used to predict the service lifetime of a turbine blade subjected to the two loading histories. The results of this study indicate that the WISPER load spectrum from northern European sites significantly underestimates the WISPER protocol load spectrum from a U.S. wind farm site, i.e., the WISPER load spectrum significantly underestimates the number and magnitude of the loads observed at a U.S. wind farm site. Further, the analysis demonstrate that the European and the U.S. fatigue material data bases are in general agreement for the prediction of tensile failures. However, for compressive failures, the two data bases are significantly different, with the U.S. data base predicting significantly shorter service lifetimes than the European data base. (au) 14 refs.

  2. Nonmutagenicity of betel leaf and its antimutagenic action against environmental mutagens.

    Science.gov (United States)

    Nagabhushan, M; Amonkar, A J; D'Souza, A V; Bhide, S V

    1987-01-01

    Betel leaf (Piper betel) water and acetone extract are nonmutagenic in S. typhimurium strains with and without S9 mix. Both the extracts suppress the mutagenicity of betel quid mutagens in a dose dependent manner. Moreover both the extracts of betel leaf reduce the mutagenicity of benzo(a)pyrene and dimethylbenzanthracene. Acetone extract is more potent than water extract in inhibiting mutagenicity of environmental mutagens.

  3. [Genetic control of the sensitivity of Aspergillus nidulans to mutagenic factors. VII. Inheritance of cross-sensitivity to different mutagenic factors by uvs-mutants].

    Science.gov (United States)

    Evseeva, G V; Kameneva, S V

    1977-01-01

    To study the inheritance of the sensitivity to UV, X-rays, methylmethanesulphonate (MMS), nitrosoguanidine (NG) and nitrous acid (NA) in five uvs mutants of Aspergillus nidulans, having multiple sensitivity to these factors, the sensitivity of recombinants obtained from crossing uvs mutants with uvs+ strain, resistant to all the factors analysed, and uvs leads to uvs+ revertants is investigated. Four uvs mutants (15, 17, 19 and 26) are found to have a nomogenic control of sensitivity to different mutagens. In one mutant (uvs11) the sensitivity to five factors is controlled by two non-linked mutations, one of them determining the sensitivity to UV, NG, NA, and the other--to X-rays and MMC. Phenotypic manifestations of uvs mutations is modified by cell genotype, both chromosomal and cytoplasmic factors being responsible for the modification. Phenotypic modification of uvs mutation results in the change to some (but not to all) mutagenic factors. It suggests, that not the product of uvs gene, but some other components of the reparation complex are modified. Otherwise, reparation of different DNA damages can be carried out by a single enzyme acting in different reparation complexes.

  4. Mutagenicity of pan residues and gravy from fried meat.

    Science.gov (United States)

    Overvik, E; Nilsson, L; Fredholm, L; Levin, O; Nord, C E; Gustafsson, J A

    1987-02-01

    Lean pork meat was fried with or without the addition of frying-fat at 200 or 250 degrees C. The pan residues were collected by washing the hot pan with boiling water. When producing thickened gravy the water was substituted by a mixture of water and flour, milk and flour or cream and flour. The basic extracts were tested for mutagenicity in Ames' Salmonella test on strain TA98 with the addition of S9 mix. High amounts of mutagenicity were found in all samples. The amounts of mutagenicity in the pan residues were at a comparable level of the amounts found in the meat crusts. Thickening of the gravy caused only small changes in the mutagenicity.

  5. Effectiveness and efficiency of certain mutagens in Linum usitatissimum L

    International Nuclear Information System (INIS)

    Lateef, M.A.; Nizam, J.

    1985-01-01

    The effectiveness and efficiency of gamma rays, hydrazine, hydroxylamine, ethylmethane sulphonate and mitomycin-C. mutagens were studied on the basis of chlorophyll mutations in Linum usitatissimum L. (author)

  6. Expert advice in case of exposure to mutagens or teratogens

    International Nuclear Information System (INIS)

    Steuber, E.D.

    1982-01-01

    To answer the question of any induced hazards in progeny by an exogeneous factor it is necessary to differentiate between mutagenic and teratogenic action. Mutations can be caused by ionisizing radiations and chemicals, e.g. cytostatic drugs. After exposure to mutagenic agents a conception should be prevented for a time of 3 months to avoid a fertilization of a germ cell that has been effected during a very sensible phase. In case of conception during mutagenic exposure it is possible to detect chromosome aberrations by prenatal diagnosis after amniocentesis. The spectrum of possible teratogens is extensive and less specific than that of mutagenic agents. Factors established as embryotoxic in man are for instance radiation, several drugs and some virus infections. They have been known to cause malformations in the fetus, if these events take place during a certain critical period of organogenesis. (orig.) [de

  7. Cytological effects of some new mutagens on rice

    International Nuclear Information System (INIS)

    Wang Cailian; Chen Qiufang; Jin Wei

    2002-01-01

    Air-dried seeds of five rice varieties were carried by recoverable satellite (RS) for space mutation and were irradiated by synchronous irradiation (soft X-rays), protons and nitrogen ions. The cytological effects were compared with that of γ-irradiation. The results indicated that all the mutagens were able to induce variation on chromosome structure in root tip cells. The space environment had a stimulating mitotic effect on root tip cells. Other mutagens had inhibiting mitotic actions. The rates of micronuclei induced by synchronous irradiation and other mutagens were higher than that by γ-rays; and the rates of chromosomal bridge were lower. Furthermore, the radiosensitivity of five varieties varied with different mutagens

  8. How stable are the mutagenic tautomers of DNA bases?

    Directory of Open Access Journals (Sweden)

    Brovarets’ O. O.

    2010-02-01

    Full Text Available Aim. To determine the lifetime of the mutagenic tautomers of DNA base pairs through the investigation of the physicochemical mechanisms of their intramolecular proton transfer. Methods. Non-empirical quantum chemistry, the analysis of the electron density by means of Bader’s atom in molecules (AIM theory and physicochemical kinetics were used. Results. Physicochemical character of the transition state of the intramolecular tautomerisation of DNA bases was investigated, the lifetime of mutagenic tautomers was calculated. Conclusions. The lifetime of the DNA bases mutagenic tautomers by 3–10 orders exceeds typical time of DNA replication in the cell (~103 s. This fact confirms that the postulate, on which the Watson-Crick tautomeric hypothesis of spontaneous transitions grounds, is adequate. The absence of intramolecular H-bonds in the canonical and mutagenic tautomeric forms determine their high stability

  9. Study of Salmonella typhimurium mutagenicity assay of (E ...

    African Journals Online (AJOL)

    Study of Salmonella typhimurium mutagenicity assay of (E)-piplartine by the Ames test. AA Morandim-Giannetti, F Cotinguiba, LO Regasini, MC Frigieri, EA Varanda, A Coqueiro, MJ Kato, VS Bolzani, M Furlan ...

  10. Effect of mutagen combined action on Chlamydomonas Reinhardtii cells. I

    International Nuclear Information System (INIS)

    Vlcek, D.; Podstavkova, S.; Dubovsky, J.

    1978-01-01

    The effect was investigated of single and combined actions of alkylnitrosourea derivatives (N-methyl-N-nitrosourea and N-ethyl-N-nitrosourea) and UV-radiation on the survival of cells of Chlamydomonas reinhardtii algae in dependence on the sequence of application of mutagens and on the given conditions of cultivation following mutagen activity. In particular, the single phases were investigated of the total lethal effect, i.e., the death of cells before division and their death after division. The most pronounced changes in dependence on the sequence of application of mutagens and on the given conditions of cultivation were noted in cell death before division. In dependence on the sequence of application of mutagens, the effect of the combined action on the survival of cells changed from an additive (alkylnitrosourea + UV-radiation) to a protective effect (UV-radiation + alkylnitrosourea). (author)

  11. Mutagenic DNA repair in Escherichia coli. Pt. 2

    International Nuclear Information System (INIS)

    Doubleday, O.P.; Bridges, B.A.; Green, M.H.L.

    1975-01-01

    The photoreversibility of UV-induced mutations to Trp + in strain Escherichia coli WP2 uvr A trp (unable to excise pyrimidine dimers) was lost at different rates during incubation in different media. In Casamino acids medium after a short initial lag, photoreversibility was lost over about one generation time; in minimal medium with tryptophan, photoreversibility persisted for more than two generations; in Casamino acids medium with pantoyl lactone photoreversibility was lost extremely slowly. The rate of loss of photoreversibility was unaffected by UV dose in either Casamino acids medium or in minimal medium. The same eventual number of induced mutants was obtained when cells were incubated for two generations in any of the three media before being transferred to selective plates supplemented with Casamino acids. Thus in each the proportion of cells capable of giving rise to a mutant was the same and only the rate at which these cells did so during post-irradiation growth varied, suggesting that there might be a specific fraction of pyrimidine dimers at a given site capable of initiating a mutagenic repair event, and that the size of this fraction is dose dependent. Segregation experiments have shown that error-prone repair appears to occur once only and is not repeated in subsequent replication cycles, in contrast to (presumed error-free) recombination repair. The results are discussed in the light of current models of UV mutagenesis. (orig.) [de

  12. The effect of Aspergillus niger mutagenization on citric acid biosynthesis

    Directory of Open Access Journals (Sweden)

    Stanisław Walisch

    2014-08-01

    Full Text Available The industrial A. niger strain producing citric acid was mutagenized with the use of new chemical mutagens: free nitroxyl radicals. Strains of higher citric acid production yield were obtained. Citric acid was produced in a shorter time compared to the initial strain. During 6-12 months of storage most of the strains preserved their positive features which proves that mutants with profitable biotechnological properties were obtained. These mutants are used in industrial process.

  13. Mutagenicity of Flavonoids Assayed by Bacterial Reverse Mutation (Ames Test

    Directory of Open Access Journals (Sweden)

    Eliana Aparecida Varanda

    2012-05-01

    Full Text Available The mutagenicity of ten flavonoids was assayed by the Ames test, in Salmonella typhimurium strains TA98, TA100 and TA102, with the aim of establishing hydroxylation pattern-mutagenicity relationship profiles. The compounds assessed were: quercetin, kaempferol, luteolin, fisetin, chrysin, galangin, flavone, 3-hydroxyflavone, 5-hydroxyflavone and 7-hydroxyflavone. In the Ames assay, quercetin acted directly and its mutagenicity increased with metabolic activation. In the presence of S9 mix, kaempferol and galangin were mutagenic in the TA98 strain and kaempferol showed signs of mutagenicity in the other strains. The absence of hydroxyl groups, as in flavone, only signs of mutagenicity were shown in strain TA102, after metabolization and, among monohydroxylated flavones (3-hydroxyflavone, 5-hydroxyflavone and 7-hydroxyflavone, the presence of hydroxyl groups only resulted in minor changes. Luteolin and fisetin also showed signs of mutagenicity in strain TA102. Finally, chrysin, which has only two hydroxy groups, at the 5-OH and 7-OH positions, also did not induce mutagenic activity in any of the bacterial strains used, under either activation condition. All the flavonoids were tested at concentrations varying from 2.6 to 30.7 nmol/plate for galangin and 12.1 to 225.0 nmol/plate for other flavonoids. In light of the above, it is necessary to clarify the conditions and the mechanisms that mediate the biological effects of flavonoids before treating them as therapeutical agents, since some compounds can be biotransformed into more genotoxic products; as is the case for galangin, kaempferol and quercetin.

  14. Mutagenicity of comfrey (Symphytum Officinale) in rat liver

    OpenAIRE

    Mei, N; Guo, L; Fu, P P; Heflich, R H; Chen, T

    2005-01-01

    Comfrey is a rat liver toxin and carcinogen that has been used as a vegetable and herbal remedy by humans. In order to evaluate the mechanisms underlying its carcinogenicity, we examined the mutagenicity of comfrey in the transgenic Big Blue rat model. Our results indicate that comfrey is mutagenic in rat liver and the types of mutations induced by comfrey suggest that its tumorigenicity results from the genotoxicity of pyrrolizidine alkaloids in the plant.

  15. Mutagenicity of comfrey (Symphytum Officinale) in rat liver.

    Science.gov (United States)

    Mei, N; Guo, L; Fu, P P; Heflich, R H; Chen, T

    2005-03-14

    Comfrey is a rat liver toxin and carcinogen that has been used as a vegetable and herbal remedy by humans. In order to evaluate the mechanisms underlying its carcinogenicity, we examined the mutagenicity of comfrey in the transgenic Big Blue rat model. Our results indicate that comfrey is mutagenic in rat liver and the types of mutations induced by comfrey suggest that its tumorigenicity results from the genotoxicity of pyrrolizidine alkaloids in the plant.

  16. Proliferating Cell Nuclear Antigen-dependent Rapid Recruitment of Cdt1 and CRL4Cdt2 at DNA-damaged Sites after UV Irradiation in HeLa Cells*

    Science.gov (United States)

    Ishii, Takashi; Shiomi, Yasushi; Takami, Toshihiro; Murakami, Yusuke; Ohnishi, Naho; Nishitani, Hideo

    2010-01-01

    The licensing factor Cdt1 is degraded by CRL4Cdt2 ubiquitin ligase dependent on proliferating cell nuclear antigen (PCNA) during S phase and when DNA damage is induced in G1 phase. Association of both Cdt2 and PCNA with chromatin was observed in S phase and after UV irradiation. Here we used a micropore UV irradiation assay to examine Cdt2 accumulation at cyclobutane pyrimidine dimer-containing DNA-damaged sites in the process of Cdt1 degradation in HeLa cells. Cdt2, present in the nucleus throughout the cell cycle, accumulated rapidly at damaged DNA sites during G1 phase. The recruitment of Cdt2 is dependent on prior PCNA chromatin binding because Cdt2 association was prevented when PCNA was silenced. Cdt1 was also recruited to damaged sites soon after UV irradiation through its PIP-box. As Cdt1 was degraded, the Cdt2 signal at damaged sites was reduced, but PCNA, cyclobutane pyrimidine dimer, and XPA (xeroderma pigmentosum, complementation group A) signals remained at the same levels. These findings suggest that Cdt1 degradation following UV irradiation occurs rapidly at damaged sites due to PCNA chromatin loading and the recruitment of Cdt1 and CRL4Cdt2, before DNA damage repair is completed. PMID:20929861

  17. Identification of a mammalian nuclear factor and human cDNA-encoded proteins that recognize DNA containing apurinic sites

    International Nuclear Information System (INIS)

    Lenz, J.; Okenquist, S.A.; LoSardo, J.E.; Hamilton, K.K.; Doetsch, P.W.

    1990-01-01

    Damage to DNA can have lethal or mutagenic consequences for cells unless it is detected and repaired by cellular proteins. Repair depends on the ability of cellular factors to distinguish the damaged sites. Electrophoretic binding assays were used to identify a factor from the nuclei of mammalian cells that bound to DNA containing apurinic sites. A binding assay based on the use of β-galactosidase fusion proteins was subsequently used to isolate recombinant clones of human cDNAs that encoded apurinic DNA-binding proteins. Two distinct human cDNAs were identified that encoded proteins that bound apurinic DNA preferentially over undamaged, methylated, or UV-irradiated DNA. These approaches may offer a general method for the detection of proteins that recognize various types of DNA damage and for the cloning of genes encoding such proteins

  18. Study of anti mutagenic and mutagenic effect of different chemicals on clinically isolated strains of pseudomonas aeruginosa

    International Nuclear Information System (INIS)

    Qureshi, A.M.; Durrani, F.; Janjua, M.

    1994-01-01

    This project was undertaken to study the effect of twelve different compounds to test their anti mutagenic and mutagenic activity against clinically isolated strains of Pseudomonas aeruginosa. The effect of these compounds was estimated by counting the number of rifampicin resistant colonies growing in a particular time in a compound. The results were interpreted by plotting graphs between 10g N/NO (Rif R Colonies/ ml) and time to estimate the forward mutation rat. The results revealed that acridine, Basic fuchsin, Caffeine, cycloheximide, Ethidium bromide and Histidine probably have an anti mutagenic effect, while Cysteine, folic acid, Ethyl methane, suplphonate, Manganous Chloride and N-nitrosodietylamine acted as mutagen. Ecoli was used as control through out the study. (author)

  19. How to eliminate non-damaging earthquakes from the results of a probabilistic seismic hazard analysis (PSHA)-A comprehensive procedure with site-specific application

    International Nuclear Information System (INIS)

    Kluegel, Jens-Uwe

    2009-01-01

    The results of probabilistic seismic hazard analyses are frequently presented in terms of uniform hazard spectra or hazard curves with spectral accelerations as the output parameter. The calculation process is based on the evaluation of the probability of exceedance of specified acceleration levels without consideration of the damaging effects of the causative earthquakes. The same applies to the empirical attenuation equations for spectral accelerations used in PSHA models. This makes interpreting and using the results in engineering or risk applications difficult. Uniform hazard spectra and the associated hazard curves may contain a significant amount of contributions of weak, low-energy earthquakes not able to damage the seismically designed structures of nuclear power plants. For the development of realistic engineering designs and for realistic seismic probabilistic risk assessments (seismic PRA) it is necessary to remove the contribution of non-damaging earthquakes from the results of a PSHA. A detailed procedure for the elimination of non-damaging earthquakes based on the CAV (Cumulative Absolute Velocity)-filtering approach was developed and applied to the results of the large-scale PEGASOS probabilistic seismic hazard study for the site of the Goesgen nuclear power plant. The procedure considers the full scope of epistemic uncertainty and aleatory variability present in the PEGASOS study. It involves the development of a set of empirical correlations for CAV and the subsequent development of a composite distribution for the probability of exceedance of the damaging threshold of 0.16 gs. Additionally, a method was developed to measure the difference in the damaging effects of earthquakes of different strengths by the ratio of a power function of ARIAS-intensity or, in the ideal case, by the ratio of the square roots of the associated strong motion durations. The procedure was applied for the update of the Goesgen seismic PRA and for the confirmation of a

  20. An active site aromatic triad in Escherichia coli DNA Pol IV coordinates cell survival and mutagenesis in different DNA damaging agents.

    Directory of Open Access Journals (Sweden)

    Ryan W Benson

    Full Text Available DinB (DNA Pol IV is a translesion (TLS DNA polymerase, which inserts a nucleotide opposite an otherwise replication-stalling N(2-dG lesion in vitro, and confers resistance to nitrofurazone (NFZ, a compound that forms these lesions in vivo. DinB is also known to be part of the cellular response to alkylation DNA damage. Yet it is not known if DinB active site residues, in addition to aminoacids involved in DNA synthesis, are critical in alkylation lesion bypass. It is also unclear which active site aminoacids, if any, might modulate DinB's bypass fidelity of distinct lesions. Here we report that along with the classical catalytic residues, an active site "aromatic triad", namely residues F12, F13, and Y79, is critical for cell survival in the presence of the alkylating agent methyl methanesulfonate (MMS. Strains expressing dinB alleles with single point mutations in the aromatic triad survive poorly in MMS. Remarkably, these strains show fewer MMS- than NFZ-induced mutants, suggesting that the aromatic triad, in addition to its role in TLS, modulates DinB's accuracy in bypassing distinct lesions. The high bypass fidelity of prevalent alkylation lesions is evident even when the DinB active site performs error-prone NFZ-induced lesion bypass. The analyses carried out with the active site aromatic triad suggest that the DinB active site residues are poised to proficiently bypass distinctive DNA lesions, yet they are also malleable so that the accuracy of the bypass is lesion-dependent.

  1. Human mutagens: evidence from paternal exposure

    International Nuclear Information System (INIS)

    Narod, S.A.; Douglas, G.R.; Nestmann, E.R.; Blakey, D.H.

    1988-01-01

    The importance of inherited mutations as a cause of human disease has been established clearly through examples of well-defined genetic anomalies, such as Down syndrome and retinoblastoma. Furthermore, it is suspected that environmental contaminants induce mutations resulting in increased risk for such defects in subsequent generations of persons exposed. The present lack of direct evidence for induced inherited genetic disorders in human beings hampers the development of risk estimation techniques for extrapolation from animal models. The most extensive prospective epidemiologic studies of inherited genetic effects have involved survivors of atomic bomb detonations and patients treated with cancer chemotherapy. In neither case has a significant elevation in inherited genetic effects or cancer been detected in the offspring of exposed individuals. Epidemiologic studies of subjects receiving chronic exposure may be confounded by the effect of maternal exposure during pregnancy. Consideration of only paternal exposure can minimize the confounding influence of teratogenicity, enhancing the resolving power of studies for inherited effects. Using this approach, retrospective (case-control) studies of childhood cancer patients have provided limited but suggestive evidence for inheritance of induced effects. Endpoints, such as congenital malformations and spontaneous abortion following paternal exposure, can also be considered as indicators of heritable mutagenic effects. For example, there is limited evidence suggesting that paternal exposure to anaesthetic gases may cause miscarriage and congenital abnormalities as a result of induced male germ cell mutations. 104 references

  2. Anti mutagenesis of chemical modulators against damage induced by reactor thermal neutrons

    International Nuclear Information System (INIS)

    Zambrano A, F.; Guzman R, J.; Garcia B, A.; Paredes G, L.; Delfin L, A.

    1999-01-01

    The mutations are changes in the genetic information whether for spontaneous form or induced by the exposure of the genetic material to certain agents, called mutagens: chemical or physical (diverse types of radiations). As well as exist a great variety of mutagens and pro mutagens (these last are agents which transform themselves in mutagens after the metabolic activation). Also several chemical compounds exist which are called antimutagens because they reduce the mutagens effect. The C vitamin or ascorbic acid (A A) presents antimutagenic and anti carcinogenic properties. On the other hand a sodium/copper salt derived from chlorophyll belonging to the porphyrin group (C L) contains a chelated metal ion in the center of molecule. It is also an antioxidant, antimutagenic and anti carcinogenic compound, it is called chlorophyllin. The objective of this work is to establish if the A A or the C L will reduce the damages induced by thermal and fast reactor neutrons. (Author)

  3. On the mutagenicity of homologous recombination and double-strand break repair in bacteriophage.

    Science.gov (United States)

    Shcherbakov, Victor P; Plugina, Lidiya; Shcherbakova, Tamara; Sizova, Svetlana; Kudryashova, Elena

    2011-01-02

    The double-strand break (DSB) repair via homologous recombination is generally construed as a high-fidelity process. However, some molecular genetic observations show that the recombination and the recombinational DSB repair may be mutagenic and even highly mutagenic. Here we developed an effective and precise method for studying the fidelity of DSB repair in vivo by combining DSBs produced site-specifically by the SegC endonuclease with the famous advantages of the recombination analysis of bacteriophage T4 rII mutants. The method is based on the comparison of the rate of reversion of rII mutation in the presence and in the absence of a DSB repair event initiated in the proximity of the mutation. We observed that DSB repair may moderately (up to 6-fold) increase the apparent reversion frequency, the effect of being dependent on the mutation structure. We also studied the effect of the T4 recombinase deficiency (amber mutation in the uvsX gene) on the fidelity of DSB repair. We observed that DSBs are still repaired via homologous recombination in the uvsX mutants, and the apparent fidelity of this repair is higher than that seen in the wild-type background. The mutator effect of the DSB repair may look unexpected given that most of the normal DNA synthesis in bacteriophage T4 is performed via a recombination-dependent replication (RDR) pathway, which is thought to be indistinguishable from DSB repair. There are three possible explanations for the observed mutagenicity of DSB repair: (1) the origin-dependent (early) DNA replication may be more accurate than the RDR; (2) the step of replication initiation may be more mutagenic than the process of elongation; and (3) the apparent mutagenicity may just reflect some non-randomness in the pool of replicating DNA, i.e., preferential replication of the sequences already involved in replication. We discuss the DSB repair pathway in the absence of UvsX recombinase. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. Dietary mutagen exposure and risk of pancreatic cancer.

    Science.gov (United States)

    Li, Donghui; Day, Rena Sue; Bondy, Melissa L; Sinha, Rashmi; Nguyen, Nga T; Evans, Douglas B; Abbruzzese, James L; Hassan, Manal M

    2007-04-01

    To investigate the association between dietary exposure to food mutagens and risk of pancreatic cancer, we conducted a hospital-based case-control study at the University of Texas M. D. Anderson Cancer Center during June 2002 to May 2006. A total of 626 cases and 530 noncancer controls were frequency matched for race, sex and age (+/-5 years). Dietary exposure information was collected via personal interview using a meat preparation questionnaire. A significantly greater portion of the cases than controls showed a preference to well-done pork, bacon, grilled chicken, and pan-fried chicken, but not to hamburger and steak. Cases had a higher daily intake of food mutagens and mutagenicity activity (revertants per gram of daily meat intake) than controls did. The daily intakes of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and benzo(a)pyrene (BaP), as well as the mutagenic activity, were significant predictors for pancreatic cancer (P = 0.008, 0.031, and 0.029, respectively) with adjustment of other confounders. A significant trend of elevated cancer risk with increasing DiMeIQx intake was observed in quintile analysis (P(trend) = 0.024). A higher intake of dietary mutagens (those in the two top quintiles) was associated with a 2-fold increased risk of pancreatic cancer among those without a family history of cancer but not among those with a family history of cancer. A possible synergistic effect of dietary mutagen exposure and smoking was observed among individuals with the highest level of exposure (top 10%) to PhIP and BaP, P(interaction) = 0.09 and 0.099, respectively. These data support the hypothesis that dietary mutagen exposure alone and in interaction with other factors contribute to the development of pancreatic cancer.

  5. Hybrid lentivirus-phiC31-int-NLS vector allows site-specific recombination in murine and human cells but induces DNA damage.

    Directory of Open Access Journals (Sweden)

    Nicolas Grandchamp

    Full Text Available Gene transfer allows transient or permanent genetic modifications of cells for experimental or therapeutic purposes. Gene delivery by HIV-derived lentiviral vector (LV is highly effective but the risk of insertional mutagenesis is important and the random/uncontrollable integration of the DNA vector can deregulate the cell transcriptional activity. Non Integrative Lentiviral Vectors (NILVs solve this issue in non-dividing cells, but they do not allow long term expression in dividing cells. In this context, obtaining stable expression while avoiding the problems inherent to unpredictable DNA vector integration requires the ability to control the integration site. One possibility is to use the integrase of phage phiC31 (phiC31-int which catalyzes efficient site-specific recombination between the attP site in the phage genome and the chromosomal attB site of its Streptomyces host. Previous studies showed that phiC31-int is active in many eukaryotic cells, such as murine or human cells, and directs the integration of a DNA substrate into pseudo attP sites (pattP which are homologous to the native attP site. In this study, we combined the efficiency of NILV for gene delivery and the specificity of phiC31-int for DNA substrate integration to engineer a hybrid tool for gene transfer with the aim of allowing long term expression in dividing and non-dividing cells preventing genotoxicity. We demonstrated the feasibility to target NILV integration in human and murine pattP sites with a dual NILV vectors system: one which delivers phiC31-int, the other which constitute the substrate containing an attB site in its DNA sequence. These promising results are however alleviated by the occurrence of significant DNA damages. Further improvements are thus required to prevent chromosomal rearrangements for a therapeutic use of the system. However, its use as a tool for experimental applications such as transgenesis is already applicable.

  6. Processing of free radical damaged DNA bases

    International Nuclear Information System (INIS)

    Wallace, S.

    2003-01-01

    Free radicals produced during the radiolysis of water gives rise to a plethora of DNA damages including single strand breaks, sites of base loss and a wide variety of purine and pyrimidine base lesions. All these damages are processed in cells by base excision repair. The oxidative DNA glycosylases which catalyze the first step in the removal of a base damage during base excision repair evolved primarily to protect the cells from the deleterious mutagenic effects of single free radical-induced DNA lesions arising during oxidative metabolism. This is evidenced by the high spontaneous mutation rate in bacterial mutants lacking the oxidative DNA glycosylases. However, when a low LET photon transverses the DNA molecule, a burst of free radicals is produced during the radiolysis of water that leads to the formation of clustered damages in the DNA molecule, that are recognized by the oxidative DNA glycosylases. When substrates containing two closely opposed sugar damages or base and sugar damages are incubated with the oxidative DNA glycosylases in vitro, one strand is readily incised by the lyase activity of the DNA glycosylase. Whether or not the second strand is incised depends on the distance between the strand break resulting from the incised first strand and the remaining DNA lesion on the other strand. If the lesions are more than two or three base pairs apart, the second strand is readily cleaved by the DNA glycosylase, giving rise to a double strand break. Even if the entire base excision repair system is reconstituted in vitro, whether or not a double strand break ensues depends solely upon the ability of the DNA glycosylase to cleave the second strand. These data predicted that cells deficient in the oxidative DNA glycosylases would be radioresistant while those that overproduce an oxidative DNA glycosylase would be radiosensitive. This prediction was indeed borne in Escherichia coli that is, mutants lacking the oxidative DNA glycosylases are radioresistant

  7. Mutagenicity of irradiated solutions of nuclei acid bases and nucleosides in Salmonella typhimurium

    International Nuclear Information System (INIS)

    Wilmer, J.; Schubert, J.

    1981-01-01

    Solutions of nucleic acid bases, nucleosides and a nucleotide, saturated with either N 2 , N 2 O or O 2 , were irradiated and tested for mutagenicity towards Salmonella typhimurium, with and without pre-incubation. Irradiated solutions of the nuclei acid bases were all non-mutagenic. Irradiated solutions of the nucleosides showed mutagenicity in S. typhimurium TA100 (pre-incubation assay). Generally, the mutagenicity followed the order: N 2 O > N 2 > O 2 . The results show that the formation of mutagenic radiolytic products is initiated by attack of mainly solutions of the nucleotide thymidine-5'-monophosphate, no mutagenicity could be detected. (orig.)

  8. The effects of mutagens on some algae

    International Nuclear Information System (INIS)

    Aranez, A.T.

    1984-01-01

    Pure cultures of Scenedesmus quadricauda (Turp.) Breb. and chlorella pyrenoidosa Chick were subjected to 0.5, 3, 6, 9 and 12 Kr gamma radiation ( 60 Co source) from the Philippine Atomic Energy Commission. Untreated cells were used as control. Dose of 0.5 Kr increased the growth rate of Scenedesmus by 3.12%, 15.27% and 20.48% during the first, third and fourth week respectively. Doses of 6, 9 and 12 decreased the growth rate by 86.33%, 70.7% and 58.2% respectively during the first week. The stimulating effect of low dose (0.5 Kr) was recovered after the fourth week while the inhibiting effect on growth by higher doses was recovered after the first week. Gamma radiation produced morphological changes in the Scenedesmus in the form of enlarged cells, cells with kidney-shape chloroplast, cells in chain, and coenobia with cells that were not in perfect alignment with each other. In chlorella, gamma radiation produced enlarged cells, cells with wrinkled surface and cells that were colourless. Ethyl methanesulfate of 0.1%, 0.4%, 0.8% and 1.25% in phosphate buffer solution was another mutagen used. Algae in distilled water and phosphate buffer were used as control. Treatment with EMS produced coenobia of Scenedesmus with cells that were twice and thrice the normal cells, cells that were rounded or oval in outline, with wavy instead of smooth margin, cells with pseudopodia-like protrusions and coenobia with abnormal number of cells. In Chlorella, EMS produced cells that were twice the size of the normal size of the normal ones, cells that were wavy in outline, abnormal in shape, and cells with no chlorophyll. Scenedesmus was more sensitive to gamma radiation and EMS than chlorella. Of the morphological changes observed, only Scenedesmus with cells around twice the size of the normal ones produced by treatment with either gamma radiation of EMS were successfully propagated. (author)

  9. Impaired recovery and mutagenic SOS-like responses in ataxia telangiectasia cells

    Energy Technology Data Exchange (ETDEWEB)

    Hilgers, G. (Universite Libre de Bruxelles (Belgium) Rijksuniversiteit Leiden (Netherlands)); Abrahams, P.J. (Rijksuniversiteit Leiden (Netherlands)); Chen, Y.Q. (Universite Libre de Bruxelles (Belgium)); Schouten, R. (Rijksuniversiteit Leiden (Netherlands)); Cornelis, J.J. (Universite Libre de Bruxelles (Belgium) Institut Pasteur, 75 - Paris (France)); Lowe, J.E. (Sussex Univ., Brighton (UK)); Eb, A.J. van der (Rijksuniversiteit Leiden (Netherlands)); Rommelaere, J. (Universite Libre de Bruxelles (Belgium) Institut Pasteur, 75 - Paris (France))

    1989-01-01

    Radiosensitive fibroblasts from patients with ataxia telangiectasia (AT) were studied for their proficiency in two putative eukaryotic SOS-like responses, namely the enhanced reactivation (ER) and enhanced mutagenesis of damaged viruses infecting pre-irradiated versus mock-treated cells. A previous report indicated that, unlike normal human cells, a line of AT fibroblasts (AT5BIVA) could not be induced to express ER of damaged parvovirus H-1, a single-stranded DNA virus, by UV- or X-irradiation. In the present study, AT5BIVA fibroblasts were also distinguished from normal cells by the inability of the former to achieve enhanced mutagenesis of damaged H-1 virus upon cell UV-irradiation. In contrast, dose-response and time-course experiments revealed normal levels of ER of Herpes simplex virus 1, a double-stranded DNA virus, in X- or UV-irradiated AT5BIVA cells. Taken together, these data point to a possible deficiency of AT cells in a conditioned mutagenic process that contributes to a greater extent to the recovery of damaged single-stranded than double-stranded DNA. Such a defect may concern the replication of damaged DNA or the generation of signals promoting the latter process and may be related to the lack of radiation-induced delay that is typical of AT cell DNA synthesis. (author).

  10. Impaired recovery and mutagenic SOS-like responses in ataxia telangiectasia cells

    International Nuclear Information System (INIS)

    Hilgers, G.; Abrahams, P.J.; Chen, Y.Q.; Schouten, R.; Cornelis, J.J.; Lowe, J.E.; Eb, A.J. van der; Rommelaere, J.

    1989-01-01

    Radiosensitive fibroblasts from patients with ataxia telangiectasia (AT) were studied for their proficiency in two putative eukaryotic SOS-like responses, namely the enhanced reactivation (ER) and enhanced mutagenesis of damaged viruses infecting pre-irradiated versus mock-treated cells. A previous report indicated that, unlike normal human cells, a line of AT fibroblasts (AT5BIVA) could not be induced to express ER of damaged parvovirus H-1, a single-stranded DNA virus, by UV- or X-irradiation. In the present study, AT5BIVA fibroblasts were also distinguished from normal cells by the inability of the former to achieve enhanced mutagenesis of damaged H-1 virus upon cell UV-irradiation. In contrast, dose-response and time-course experiments revealed normal levels of ER of Herpes simplex virus 1, a double-stranded DNA virus, in X- or UV-irradiated AT5BIVA cells. Taken together, these data point to a possible deficiency of AT cells in a conditioned mutagenic process that contributes to a greater extent to the recovery of damaged single-stranded than double-stranded DNA. Such a defect may concern the replication of damaged DNA or the generation of signals promoting the latter process and may be related to the lack of radiation-induced delay that is typical of AT cell DNA synthesis. (author)

  11. Two nitro derivatives of azabenzo[a]pyrene N-oxide: Electronic properties and their relation to mutagenic activity

    Energy Technology Data Exchange (ETDEWEB)

    Ostojić, Bojana D., E-mail: bostojic@chem.bg.ac.rs; Đorđević, Dragana S.

    2015-03-21

    Highlights: • Molecular properties of nitro isomers of azabenzo[a]pyrene N-oxide are investigated. • Stability, ionization potential, electron affinity, and polarizability are determined. • High quality DFT methods are employed. • Nitroreduction, oxidation, and polarizability are not crucial for mutagenicity. • Dipole moment and electronic charge distribution are important for characterization. - Abstract: The equilibrium geometries, relative energies, IR and Raman spectra, vertical ionization potentials (IP), vertical electron affinities (EA), dipole moments (μ), electronic dipole polarizabilities (α), and molecular electrostatic potentials (MEP) of two species that show very high mutagenicity, 1-nitro-6-azabenzo[a]pyrene N-oxide (1-N-6-ABPO) and 3-nitro-6-azabenzo[a]pyrene N-oxide (3-N-6-ABPO), are investigated by means of Density Functional Theory (DFT) using B3LYP functional with different basis sets. The 3-N-6-ABPO isomer was estimated to be much more mutagenic in Salmonella typhimurium tester strain TA98 (396 000 revertants/nmol) than 1-N-6-ABPO (36 100 revertants/nmol) (Fukuhara et al., 1992). The results show that for both isomers the structural, energetic, and vibrational properties are similar. The orientation of the nitro group with respect to the plane of the aromatic system as well as the nitroreduction and oxidation reaction and polarizability seem not be important for the determination of different mutagenic behavior of these isomers. However, the dipole moment of 3-N-6-ABPO is about 3 times that of 1-N-6-ABPO. The larger dipole moment and the different electronic charge distribution of 3-N-6-ABPO compared to 1-N-6-ABPO imply stronger electrostatic and inductive molecular interactions so that the active site of the enzyme involved in the mutagenic activation can more effectively bind 3-N-6-ABPO compared to 1-N-6-ABPO.

  12. Desleucyl-Oritavancin with a Damaged d-Ala-d-Ala Binding Site Inhibits the Transpeptidation Step of Cell-Wall Biosynthesis in Whole Cells of Staphylococcus aureus.

    Science.gov (United States)

    Kim, Sung Joon; Singh, Manmilan; Sharif, Shasad; Schaefer, Jacob

    2017-03-14

    We have used solid-state nuclear magnetic resonance to characterize the exact nature of the dual mode of action of oritavancin in preventing cell-wall assembly in Staphylococcus aureus. Measurements performed on whole cells labeled selectively in vivo have established that des-N-methylleucyl-N-4-(4-fluorophenyl)benzyl-chloroeremomycin, an Edman degradation product of [ 19 F]oritavancin, which has a damaged d-Ala-d-Ala binding aglycon, is a potent inhibitor of the transpeptidase activity of cell-wall biosynthesis. The desleucyl drug binds to partially cross-linked peptidoglycan by a cleft formed between the drug aglycon and its biphenyl hydrophobic side chain. This type of binding site is present in other oritavancin-like glycopeptides, which suggests that for these drugs a similar transpeptidase inhibition occurs.

  13. Cooking with Fire: The Mutagenicity- and PAH-Emission ...

    Science.gov (United States)

    Emissions from solid fuels used for cooking cause ~4 million premature deaths per year. Advanced solid-fuel cookstoves are a potential solution, but they should be assessed by appropriate performance indicators, including biological effects. We evaluated two categories of solid-fuel cookstoves for 8 pollutant- and 4 mutagenicity-emission factors, correlated the mutagenicity-emission factors, and compared them to those of other combustion emissions. We burned red oak in a 3-stone fire (TSF), a natural-draft stove (NDS), and a forced-draft stove (FDS); we combusted propane as a liquified petroleum gas control fuel. We determined emission factors based on useful energy (megajoules delivered, MJd) for carbon monoxide, nitrogen oxides (NOx), black carbon, methane, total hydrocarbons, 32 polycyclic aromatic hydrocarbons, PM2.5, levoglucosan (a wood-smoke marker), and mutagenicity in Salmonella. Other than NOx the emission factors per MJd correlated highly among each other (r2 ≥ 0.92); NOx correlated 0.58-0.76 with the other emission factors. Excluding NOx, the NDS and FDS reduced the emission factors on average 68 and 92%, respectively, relative to the TSF. Nonetheless, the mutagenicity-emission factor based on fuel energy used (MJthermal) for the most efficient stove (FDS) was intermediate to that of a large diesel bus engine and a small diesel generator. Both mutagenicity- and pollutant-emission factors may be informative for characterizing cookstove

  14. Effects of diet composition on mutagenic activity in urine.

    Science.gov (United States)

    Ohara, Akihiro; Matsuhisa, Tsugio

    2004-01-01

    The effects of dietary habits on mutagenic activity in urine were investigated using the umu test based on the use of the genetically engineered bacteria Salmonella typhimurium TA 1535 pSK1002. Genotoxic effects in sample urine were detected by measuring the activation of the SOS response in the bacteria and recording the beta- galactosidase activity. Human subjects consisted of smokers and non-smokers. Urine from subjects who consumed fish showed the highest mutagenic activity, followed by the urine samples from subjects who ate pork or beef. Chicken induced a low level of mutagenic activity. When the subjects ate fried or roasted animal foods, the urine samples gave higher mutagenicity than the urine samples from the subject who consumed non-fried or non-roasted animal foods. When the subject ate vegetables along with a diet rich in animal foods, the activity in urine decreased. Herbs and spices gave the same tendency toward decline as vegetables. Non-smoker urine shower mutagenic activity than samples from smokers.

  15. Size of and damage on shoots of Passiflora suberosa (Passifloraceae influence oviposition site selection of Heliconius erato phyllis (Fabricius (Lepidoptera, Nymphalidae

    Directory of Open Access Journals (Sweden)

    Elna Mugrabi-Oliveira

    1996-01-01

    Full Text Available Oviposition site selection of Heliconius erato phyllis (Fabricius, 1775 (Lepidoptera, Nymphalidae was studied when size of and damage on shoots were variable in a natural population of Passiflora suberosa Linnaeus (Passifloraceae, and through sequential and simultaneous choice experiments performed under insectary conditions. Females showed marked oviposition preference for undamaged and largest shoots of P. suberosa. Eggs were mostly laid on the terminal buds of intact shoots under natural conditions. In simultaneous choice trials, females preferred to oviposit on shoots from which leaves (ten were removed but the terminal bud maintained to those where leaves were kept but the terminal bud was cut out. In sequential choice trials, they did not lay eggs on shoots from which the terminal bud was removed. Females preferred to oviposit on large to short intact shoots in both sequential and simultaneous choice trials. Females laid eggs preferentially on shoots with the greatest leaf area when most plants were intact in the field during early spring. Later in fall, when mostly large, old shoots were damaged or in a reproductive stage (less desirable for oviposition, oviposition intensity was highest on the shortest, youngest shoots of P. suberosa. Thus, females might rank these quality attributes higher than size while selecting shoots for oviposition. The consequences of ovipositing selectively on intact, large shoots of P. suberosa are discussed from the view point of H. erato phyllis larval performance.

  16. Updated synthesis of the knowledge about the impact on marine environment of the radioactive releases from Fukushima Dai-ichi damaged site - October 26, 2011

    International Nuclear Information System (INIS)

    2011-01-01

    A strong radioactive contamination of the marine environment close to the damaged Fukushima Dai-ichi power plant has been observed since March 21. The high concentration of some nuclides ( 131 I, 137 Cs, 134 Cs, 136 Cs, 132 Te, 132 I) comes from three possible sources: the liquid effluents from the damaged site, the atmospheric fallouts, and the weathering of contaminated soils. This information note presents and comments the most recent informations gathered by the French institute of radiation protection and nuclear safety (IRSN) since the previous information note from July 11 and devoted to the same topic. It presents the estimation of the relative contribution of each contamination source and the evolution with time of the marine contamination. The mapping of 137 Cs concentrations in surface seawater allows to estimate the amount of total 137 Cs in the marine environment and its evolution with time. 137 Cs and 134 Cs concentrations were measured both in samples of surface coastal sediments and in river fishes and seafood products (mainly fishes and molluscs). Results are reported in graphs showing their evolution with time. (J.S.)

  17. Mutagenic potential scale developed for relative evaluation of biological system response to environments presenting different gamma exposure rates

    International Nuclear Information System (INIS)

    Nouailhetas, Yannick; Almeida, Carlos E. Bonacossa de; Mezrahi, Arnaldo; Shu, Jane; Xavier, Ana Maria

    1999-01-01

    The elaboration of a mutagenic potential scale (MPS) will be accomplished through the evaluation of the frequency of induced mutations in a plant biological system in different sites. The selection of these sites will be based on general public perception of risk to health. In this selection, it will include areas such ecological paradises and also neighborhoods of nuclear reactors and uranium mining and milling industry with potential radiological impact. The developed project foresees the contribution of other research groups that will also provide data from different sites. The referred scale will be built based on the response of the genetic system that gives color to the cells of Tradescantia (BNL 4430) stamen hair to mutagenic agents. Methodological improvements has been developed aiming the computerization of mutagenic events evaluation and statistical analysis of data that will significantly increase the efficiency of the system and obtention of results. Other biological systems of environmental quality are being added to the project, for future use. MPS should facilitate the general public and professionals of the nuclear area to understand risks, on a biological basis, of exposure from radiologically impacted environments. (author)

  18. Protective Effect of Prolactin against Methylmercury-Induced Mutagenicity and Cytotoxicity on Human Lymphocytes

    Directory of Open Access Journals (Sweden)

    Liz Carmem Silva-Pereira

    2014-09-01

    Full Text Available Mercury exhibits cytotoxic and mutagenic properties as a result of its effect on tubulin. This toxicity mechanism is related to the production of free radicals that can cause DNA damage. Methylmercury (MeHg is one of the most toxic of the mercury compounds. It accumulates in the aquatic food chain, eventually reaching the human diet. Several studies have demonstrated that prolactin (PRL may be differently affected by inorganic and organic mercury based on interference with various neurotransmitters involved in the regulation of PRL secretion. This study evaluated the cytoprotective effect of PRL on human lymphocytes exposed to MeHg in vitro, including observation of the kinetics of HL-60 cells (an acute myeloid leukemia lineage treated with MeHg and PRL at different concentrations, with both treatments with the individual compounds and combined treatments. All treatments with MeHg produced a significant increase in the frequency of chromatid gaps, however, no significant difference was observed in the chromosomal breaks with any treatment. A dose-dependent increase in the mitotic index was observed for treatments with PRL, which also acts as a co-mitogenic factor, regulating proliferation by modulating the expression of genes that are essential for cell cycle progression and cytoskeleton organization. These properties contribute to the protective action of PRL against the cytotoxic and mutagenic effects of MeHg.

  19. Protective Effect of Prolactin against Methylmercury-Induced Mutagenicity and Cytotoxicity on Human Lymphocytes

    Science.gov (United States)

    Silva-Pereira, Liz Carmem; da Rocha, Carlos Alberto Machado; Cunha, Luiz Raimundo Campos da Silva e; da Costa, Edmar Tavares; Guimarães, Ana Paula Araújo; Pontes, Thais Brilhante; Diniz, Domingos Luiz Wanderley Picanço; Leal, Mariana Ferreira; Moreira-Nunes, Caroline Aquino; Burbano, Rommel Rodríguez

    2014-01-01

    Mercury exhibits cytotoxic and mutagenic properties as a result of its effect on tubulin. This toxicity mechanism is related to the production of free radicals that can cause DNA damage. Methylmercury (MeHg) is one of the most toxic of the mercury compounds. It accumulates in the aquatic food chain, eventually reaching the human diet. Several studies have demonstrated that prolactin (PRL) may be differently affected by inorganic and organic mercury based on interference with various neurotransmitters involved in the regulation of PRL secretion. This study evaluated the cytoprotective effect of PRL on human lymphocytes exposed to MeHg in vitro, including observation of the kinetics of HL-60 cells (an acute myeloid leukemia lineage) treated with MeHg and PRL at different concentrations, with both treatments with the individual compounds and combined treatments. All treatments with MeHg produced a significant increase in the frequency of chromatid gaps, however, no significant difference was observed in the chromosomal breaks with any treatment. A dose-dependent increase in the mitotic index was observed for treatments with PRL, which also acts as a co-mitogenic factor, regulating proliferation by modulating the expression of genes that are essential for cell cycle progression and cytoskeleton organization. These properties contribute to the protective action of PRL against the cytotoxic and mutagenic effects of MeHg. PMID:25247425

  20. Mutagenicity of the Musa paradisiaca (Musaceae) fruit peel extract in mouse peripheral blood cells in vivo.

    Science.gov (United States)

    Andrade, C U B; Perazzo, F F; Maistro, E L

    2008-01-01

    Plants are a source of many biologically active products and nowadays they are of great interest to the pharmaceutical industry. In the present study, the mutagenic potential of the Musa paradisiaca fruit peel extract was assessed by the single-cell gel electrophoresis (SCGE) and micronucleus assays. Animals were treated orally with three different concentrations of the extract (1000, 1500, and 2000 mg/kg body weight). Peripheral blood cells of Swiss mice were collected 24 h after treatment for the SCGE assay and 48 and 72 h for the micronucleus test. The results showed that the two higher doses of the extract of M. paradisiaca induced statistically significant increases in the average numbers of DNA damage in peripheral blood leukocytes for the two higher doses and a significant increase in the mean of micronucleated polychromatic erythrocytes in the three doses tested. The polychromatic/normochromatic erythrocyte ratio scored in the treated groups was not statistically different from the negative control. The data obtained indicate that fruit peel extract from M. paradisiaca showed mutagenic effect in the peripheral blood cells of Swiss albino mice.

  1. Mutagenicity studies on alcohol extracts from gamma-irradiated potatoes

    International Nuclear Information System (INIS)

    Ishidate, M. Jr.; Yoshikawa, Kunie; Sofuni, Toshio; Iwahara, Shigeo; Sibuya, Tohru.

    1981-01-01

    The alcohol extracts freshly prepared from gamma-irradiated potatoes were examined for their mutagenic activity in bacterial and mammalian cell systems. Negative results were obtained from all following test systems: Mutation assays with Salmonella typhimurium His - strains such as TA 100, TA 98, TA 1535, TA 1537, and streptomycin-dependent mutant (SM sup(d)) strain, TA 100 - 10, inductests with Escherichia coli strains, K 12 GY 5027 and K 12 C600, chromosomal aberration tests with Chinese hamster cells in culture, as well as micronucleus tests in mice. In addition, no difference in the mutagenic activities was found between extracts prepared from the irradiated and the unirradiated potatoes, suggesting that no mutagenic substance was produced in potatoes following gamma-irradiation. (author)

  2. Optimal Mutagen Doses for Emiliania huxleyi

    Science.gov (United States)

    Byrne, P.

    2016-02-01

    Emiliania huxleyi (E. huxleyi) is one of the most prominent coccolithophores. Given favorable conditions, E. huxleyi blooms can reach sizes exceeding 100,000km2, with densities of 107 cells per L (Olson & Strom 2002). With increasing demand and limited supply of fossil fuels, it has become increasingly popular to look toward alternative renewable fuel sources. E. Huxleyi store energy predominately as uniquely structured polyunsaturated long chain (C37-39) alkenes, alkenones and alkenoates (abbreviated as PULCAs) (Eltgroth et al 2005). Unlike the stored energy of macroalgae and higher order plants, triacylglycerols (TAGs), PULCAs provide a similar composition to native petroleum crude oils (Yamane 2013), which offers a more cost effective and higher yielding extraction process (Wu et al 1999). A number of factors have been shown to influence the alkenone content of E. huxleyi, such as nitrogen deficiency, phosphate limitation (Li et al 2014), and temperature (Shiraiwa et al 2005). For these reasons E. huxleyi has the potential to be an attractive system for algal biofuel. The broad and long-term objective of our research is to elucidate the alkenone biosynthesis pathway in E. Huxleyi, using random mutagenesis techniques. We propose to use UV light and methylmethane sulfonate (MMS) to create a mutant population, from which clones unable to synthesize alkenones will be selected. Identifying genes whose specific mutations underlie the loss-of-function phenotype will then reveal genes of interest. The aim of this research was to determine the UV and MMS dose response rates for E. huxleyi to ascertain optimal doses defined as a 50% survival rate for each of the two mutagens. Preliminary data indicate that E. huxleyi appear to be highly sensitive to UV mutagenesis, with an LD50 of 0.57mJ/cm2 for the calcifying strain M217 and 0.96mJ/cm2 for the non-calcifying strain CCMP1516. Both calcifying and non-calcifying strains exhibit similar LD50 values for MMS at 1-2% (v/v).

  3. Mutagenicity of heated sugar-casein systems: effect of the Maillard reaction.

    Science.gov (United States)

    Brands, C M; Alink, G M; van Boekel, M A; Jongen, W M

    2000-06-01

    The formation of mutagens after the heating of sugar-casein model systems at 120 degrees C was examined by the Ames test, using Salmonella typhimurium strain TA100. Several sugars (glucose, fructose, galactose, tagatose, lactose, and lactulose) were compared in their mutagenicities. Mutagenicity could be fully ascribed to Maillard reaction products and strongly varied with the kind of sugar. The differences in mutagenicity among the sugar-casein systems were caused by a difference in reaction rate and a difference in reaction mechanism. Sugars with a comparable reaction mechanism (glucose and galactose) showed a higher mutagenic activity corresponding with a higher Maillard reactivity. Disaccharides showed no mutagenic activity (lactose) or a lower mutagenic activity (lactulose) than their corresponding monosaccharides. Ketose sugars (fructose and tagatose) showed a remarkably higher mutagenicity compared with their aldose isomers (glucose and galactose), which was due to a difference in reaction mechanism.

  4. DECOVALEX-THMC Project. Task C. Excavation Damaged Zone (EDZ) in argillaceous rock at Tournemire site (France). Report of Task C1

    Energy Technology Data Exchange (ETDEWEB)

    Rejeb, A. (comp.) [Inst. of Radioprotection and Nuclear Safety (France); Stephansson, O. (comp.) [GeoForschungsZentrum-Potsdam (Germany); Millard, A. [CEA/IRSN (France); Ziefle, G.; Kohlmeier, M.; Massmann, J.; Zielke, W. [ISEB/BGR (Germany); Uehara, S.; Kobayashi, A.; Chijimatsu, M.; Fujita, T. [KU/JAEA (Japan)

    2007-02-15

    The DECOVALEX-THMC project is an ongoing international co-operative project that was stared in 2004 to support the development of mathematical models of coupled Thermal (T), Hydrological (H), Mechanical (M) and Chemical (C) processes in geological media for siting potential nuclear fuel waste repositories. The general objective is to characterise and evaluate the coupled THMC processes in the near field and far field of a geological repository and to assess their impact on performance assessment: - during the three phases of repository development: excavation phase, operation phase and post-closure phase; - for three different rocks types: crystalline, argillaceous and tuff; - with specific focus on the issues of: Excavation Damaged Zone (EDZ), permanent property changes of rock masses, and glaciation and permafrost phenomena. This report describes the results of Task C1 of the project devoted to Excavation Damage Zone (EDZ) in argillaceous rock at the Tournemire site in France. The task is to develop adequate numerical models for interpretation of observed damaged zones around three different openings excavated at different time at the Tournemire site. The research teams are asked to model the evolution of the EDZ with time and to compare the results with measurements performed at the site. Three research teams are participating in this task: - CEA (Commissariat of Atomic Energy, France) and the IRSN (Institute of Radioprotection and Nuclear safety, France) ; - ISEB (Institute of Fluid Mechanics and Computer Applications in Civil Engineering, University of Hanover, Germany) supported by the BGR (Federal Institute for Geosciences and Natural Resources, Germany); - KU (Department of Urban and Environmental Engineering, Kyoto University, Japan) supported by the JAEA (Japan Atomic Energy Agency, Japan). This report presents a description and definition of Task C including a geological description of the site, the geomechanical characterisation of the argillaceous

  5. Determining effective radiation mutagen dose for garlic (Allium sativum L.)

    International Nuclear Information System (INIS)

    Taner, Y.; Kunter, B.

    2004-01-01

    This study was carried out to get database for future garlic mutation breeding studies. For this aim, 0, 5, 10, 15, 20, 25 and 30 Gy doses of Cs 137 (gamma-ray) were applied on garlic cloves as a physical mutagen. 50 cloves were used for each dose. Sixty days after treatment, germination rate and shoot development of cloves were determined. The Effective Mutagen Dose (ED 50 ) was calculated by regression analyses. According to the results, 4.455 Gy dose was found to be effective as ED 50 . (author)

  6. Mutagen induced variability in Ragi (Eleucine coracana Gaertn)

    International Nuclear Information System (INIS)

    Haider, Z.A.; Mahto, J.L.; Kumar, Binod

    1996-01-01

    Varieties A-404 and HR-374 of Ragi (Eleucine coracana Gaertn) when subjected to different doses of gamma rays, EMS and their combination treatments showed a linear reverse relationship between doses and germination percentage. The same was true for seedling survival and pollen fertility. Variety A-404 proved to be more sensitive to all mutagenic treatments as compared to the variety HR-374. There was, however, a general gain with respect to panicle length in most of the treatments, where as for a number of fingers per panicle no order could be observed in any of the mutagen used. (author). 10 refs., 2 tabs

  7. Study on increasing mutagenic efficiency of radiation breeding for rice

    International Nuclear Information System (INIS)

    Wan Xianguo; Pang Boliang; Zhu Xiaoqi

    1993-04-01

    Increasing mutagenic efficiency and improving selection method are of important topics for crop mutation breeding. Investigation on the radiation breeding for rice (Oryza Sativa L.) showed that the crossing in combination with gamma ray irradiation or laser irradiation and proper selection of dosage rate can increase mutagenic efficiency. According to the correlation of phenotype in M 1 generation and mutation frequency in M 2 for rice, the materials with certain characters were chose as seeds, thus the works of generation selections will be reduced

  8. Environmental chemical mutagens and genetic risks: Lessons from radiation genetics

    International Nuclear Information System (INIS)

    Sankaranarayanan, K.

    1996-01-01

    The last three decades have witnessed substantial progress in the development and use of a variety of in vitro and in vivo assay systems for the testing of environmental chemicals which may pose a mutagenic hazard to humans. This is also true of basic studies in chemical mutagenesis on mechanisms, DNA repair, molecular dosimetry, structure-activity relationships, etc. However, the field of quantitative evaluation of genetic risks of environmental chemicals to humans is still in it infancy. This commentary addresses the question of how our experience in estimating genetic risks of exposure to ionizing radiation can be helpful in similar endeavors with environmental chemical mutagens. 24 refs., 3 tabs

  9. Mutagenic activity of airborne particulate matter from the urban area of Porto Alegre, Brazil

    Directory of Open Access Journals (Sweden)

    Vera Maria Ferrão Vargas

    1998-06-01

    Full Text Available The mutagenic activity of airborne particulate matter collected from three different sites within the urban area of Porto Alegre, Brazil, was investigated using a Salmonella/microsome assay. Samples were extracted by sonication, sequentially, with cyclohexane (CX, and dichloromethane (DCM, for a rough fractionation by polarity. The different fractions were tested for mutagenicity using Salmonella typhimurium strains TA98, with and without metabolic activation (S9 mix fraction, and TA98NR and TA98/1,8-DNP6, without metabolic activation. Mutagenic response was observed for frameshift strain TA98 in assays with and without metabolization for two sites (sites 2 and 3, which had considerable risk of environmental contamination by nonpolar (CX and/or moderately polar (DCM compounds. However, the values of revertants/m3 (rev/m3 were highest on the site subject to automobile exhaust (site 3 in assays without (9.56 rev/m3 and with metabolization (5.08 rev/m3. Maximum mutagenic activity was detected in the moderately polar fraction, decreasing after metabolization. Nevertheless, the nonpolar fractions (CX gave higher mutagenic activity in the presence of metabolization than in the absence of the S9 mix fraction. The responses observed for TA98NR and TA98/1,8-DNP6 strains suggest the activity of nitrocompounds.Foi investigada a atividade mutagênica de material particulado de amostras de ar coletadas em três diferentes locais dentro da área urbana da cidade de Porto Alegre, Brasil, através do ensaio Salmonella/microssoma. As amostras foram extraídas, em ultra-som, por fracionamento seqüencial de acordo com a polaridade, utilizando os solventes ciclohexano (CX e diclorometano (DCM. As diferentes frações foram testadas para mutagenicidade com as linhagens de Salmonella typhimurium TA98, em presença e ausência de ativação metabólica, e TA98NR e TA98/1,8-DNP6 em ausência de metabolização. Observou-se resposta mutagênica positiva, do tipo erro

  10. 40 Years of the Salmonella Mutagenicity Assay: Implications for 21st Century Toxicology

    Science.gov (United States)

    The Salmonella (Ames) mutagenicity assay was developed and introduced by Bruce Ames and colleagues in 1971. Since then, it has become the standard assay for hazard identification of mutagens worldwide. It is a first-tier test for mutagenic activity in the pharmaceutical and chemi...

  11. Mutagenic and antimutagenic activities of bioflavonoids and structural analogues in the Ames/Salmonella test

    NARCIS (Netherlands)

    Mohn GR; Van der Stel JJ; Stavenuiter JFC; Hamzink MRJ; Kreijl CF; LEO; LBO

    1996-01-01

    The mutagenic and antimutagenic properties of bioflavonoids were determined in the bacterial mutagenicity test of Ames, using Salmonella typhimurium strains TA98 and TA100. The decreasing order of mutagenic activity found in both strains was quercetin>myricetin-kaempferol>morin hydrate. The

  12. Mutagenicity of heated sugar-casein systems : effect of the Maillard :reaction

    NARCIS (Netherlands)

    Brands, C.M.J.; Alink, G.M.; Boekel, van M.A.J.S.; Jongen, W.M.F.

    2000-01-01

    The formation of mutagens after the heating of sugar-casein model systems at 120 C was examined by the Ames test, using Salmonella typhimurium strain TA100. Several sugars (glucose, fructose, galactose, tagatose, lactose, and lactulose) were compared in their mutagenicities. Mutagenicity could be

  13. Spontaneous and mutagen-induced deletions: mechanistic studies in Salmonella tester strain TA102

    International Nuclear Information System (INIS)

    Levin, D.E.; Marnett, L.J.; Ames, B.N.

    1984-01-01

    Salmonella tester strain TA102 carries the hisG428 ochre mutation on the multicopy plasmid pAQ1. DNA sequence analysis of 45 spontaneous revertants of hisG428 on the chromosome in the presence of pKM101 (strain TA103) indicates that hisG428 revertants fall into three major categories: (i) small, in-frame deletions (3 or 6 base pairs) that remove part or all of the ochre triplet; (ii) base substitution mutations at the ochre site; (iii) extragenic ochre suppressors. Deletion revertants are identified in a simple phenotypic screen by their resistance to the inhibitory histidine analog thiazolealanine, which feedback inhibits the wild-type hisG enzyme but not the enzyme resulting from the deletions. The effect of various genetic backgrounds on the generation of spontaneous deletion revertants was examined. The presence of a uvrB mutation or a recA mutation suppressed the generation of spontaneous deletion revertants to approximately 1/2.5. When hisG428 was in multiple copies on pAQ1, the frequency of spontaneous deletion revertants increased by 40-fold, which is the approximate copy number of pAQ1. Mutagenic agents that induce single-strand breaks in DNA (e.g., x-rays, bleomycin, and nalidixic acid) induced deletion revertants in TA102. These agents induced deletion revertants only in hisG428 on pAQ1 and only in the presence of pKM101. Deletion revertants were not induced by frameshift mutagens (i.e., ICR-191 and 9aminoacridine). These results indicate that different pathways exist for the generation of spontaneous and mutagen-induced deletion revertants of hisG428. 41 references, 2 figures, 3 tables

  14. Topology of evolving, mutagenized viral populations: quasispecies expansion, compression, and operation of negative selection.

    Science.gov (United States)

    Ojosnegros, Samuel; Agudo, Rubén; Sierra, Macarena; Briones, Carlos; Sierra, Saleta; González-López, Claudia; Domingo, Esteban; Cristina, Juan

    2008-07-17

    The molecular events and evolutionary forces underlying lethal mutagenesis of virus (or virus extinction through an excess of mutations) are not well understood. Here we apply for the first time phylogenetic methods and Partition Analysis of Quasispecies (PAQ) to monitor genetic distances and intra-population structures of mutant spectra of foot-and-mouth disease virus (FMDV) quasispecies subjected to mutagenesis by base and nucleoside analogues. Phylogenetic and PAQ analyses have revealed a highly dynamic variation of intrapopulation diversity of FMDV quasispecies. The population diversity first suffers striking expansions in the presence of mutagens and then compressions either when the presence of the mutagenic analogue was discontinued or when a mutation that decreased sensitivity to a mutagen was selected. The pattern of mutations found in the populations was in agreement with the behavior of the corresponding nucleotide analogues with FMDV in vitro. Mutations accumulated at preferred genomic sites, and dn/ds ratios indicate the operation of negative (or purifying) selection in populations subjected to mutagenesis. No evidence of unusually elevated genetic distances has been obtained for FMDV populations approaching extinction. Phylogenetic and PAQ analysis provide adequate procedures to describe the evolution of viral sequences subjected to lethal mutagenesis. These methods define the changes of intra-population structure more precisely than mutation frequencies and Shannon entropies. PAQ is very sensitive to variations of intrapopulation genetic distances. Strong negative (or purifying) selection operates in FMDV populations subjected to enhanced mutagenesis. The quantifications provide evidence that extinction does not imply unusual increases of intrapopulation complexity, in support of the lethal defection model of virus extinction.

  15. Topology of evolving, mutagenized viral populations: quasispecies expansion, compression, and operation of negative selection

    Directory of Open Access Journals (Sweden)

    Sierra Saleta

    2008-07-01

    Full Text Available Abstract Background The molecular events and evolutionary forces underlying lethal mutagenesis of virus (or virus extinction through an excess of mutations are not well understood. Here we apply for the first time phylogenetic methods and Partition Analysis of Quasispecies (PAQ to monitor genetic distances and intra-population structures of mutant spectra of foot-and-mouth disease virus (FMDV quasispecies subjected to mutagenesis by base and nucleoside analogues. Results Phylogenetic and PAQ analyses have revealed a highly dynamic variation of intrapopulation diversity of FMDV quasispecies. The population diversity first suffers striking expansions in the presence of mutagens and then compressions either when the presence of the mutagenic analogue was discontinued or when a mutation that decreased sensitivity to a mutagen was selected. The pattern of mutations found in the populations was in agreement with the behavior of the corresponding nucleotide analogues with FMDV in vitro. Mutations accumulated at preferred genomic sites, and dn/ds ratios indicate the operation of negative (or purifying selection in populations subjected to mutagenesis. No evidence of unusually elevated genetic distances has been obtained for FMDV populations approaching extinction. Conclusion Phylogenetic and PAQ analysis provide adequate procedures to describe the evolution of viral sequences subjected to lethal mutagenesis. These methods define the changes of intra-population structure more precisely than mutation frequencies and Shannon entropies. PAQ is very sensitive to variations of intrapopulation genetic distances. Strong negative (or purifying selection operates in FMDV populations subjected to enhanced mutagenesis. The quantifications provide evidence that extinction does not imply unusual increases of intrapopulation complexity, in support of the lethal defection model of virus extinction.

  16. Genotoxicity studies in semiconductor industry. 1. In vitro mutagenicity and genotoxicity studies of waste samples resulting from plasma etching

    Energy Technology Data Exchange (ETDEWEB)

    Braun, R.; Huettner, E.M.; Merten, H.; Raabe, F. (Institute of Plant Genetics and Crop Plant Research, Gatersleben (Germany))

    1993-07-01

    Solid waste samples taken from the etching reactor, the turbo pump, and the waste air system of a plasma etching technology line in semiconductor production were studied as to their genotoxic properties in a bacterial repair test, in the Ames/Salmonella microsome assay, in the SOS chromotest, in primary mouse hepatocytes, and in Chinese hamster V79 cell cultures. All three waste samples were found to be active by inducing of unscheduled DNA-synthesis in mouse hepatocytes in vitro. In the bacterial rec-type repair test with Proteus mirabilis, waste samples taken from the turbo pump and the vacuum pipe system were not genotoxic. The waste sample taken from the chlorine-mediated plasma reactor was clearly positive in the bacterial repair assay and in the SOS chromotest with Escherichia coli. Mutagenic activity was demonstrated for all samples in the presence and absence of S9 mix made from mouse liver homogenate. Again, highest mutagenic activity was recorded for the waste sample taken from the plasma reactor, while samples collected from the turbo pump and from the waste air system before dilution and liberation of the air were less mutagenic. For all samples chromosomal damage in V79 cells was not detected, indicating absence of clastogenic activity in vitro. Altogether, these results indicate generation of genotoxic and mutagenic products as a consequence of chlorine-mediated plasma etching in the microelectronics industry and the presence of genotoxins even in places distant from the plasma reactor. Occupational exposure can be expected both from the precipitated wastes and from chemicals reaching the environment with the air stream.

  17. The mutagenic effect of near ultraviolet light on the nvs strains of Aspergillus nidulans in the presence of 8-metoxypsoralen or angelicin

    International Nuclear Information System (INIS)

    Muronets, E.M.; Kovtunenko, L.V.; Kameneva, S.V.

    1980-01-01

    The mutual mutagenic effect of long-wave ultraviolet radiation (EUV) with angelicin which forms monoadducts in DNA and 8-metoxypsoralen (8 MOP) which forms monoadducts and joints, on conidia of uvs- and uvs+ strains of Aspergillus nidulans, is studied. The two types of interaction are shown to induce mutations intensively. Mutation induction with angelicin shows the role of psoralen pyrimidine monoadducts in mutagenesis. The technique of fractionated EUV radiation and studying the effect of monoadduct repair effectiveness on mutation output permits to prove that interthread DNA joints induced by 8-MOP+EUV are also highly mutagenous. The products of UVS/2, 20b, 26 genes which take part in the excision of DNA damages do not take part in the formation of mutations induced in aspergil by furocoumarine + EUV. The products of uvs 19, 20a genes which take part in the postreplicative DNA reduction are neccessary for the repair of premutation damages induced by furocoumarine + EUV

  18. Imaging San Jacinto Fault damage zone structure using dense linear arrays: application of ambient noise tomography, Rayleigh wave ellipticity, and site amplification

    Science.gov (United States)

    Wang, Y.; Lin, F. C.; Allam, A. A.; Ben-Zion, Y.

    2017-12-01

    The San Jacinto fault is presently the most seismically active component of the San Andreas Transform system in Southern California. To study the damage zone structure, two dense linear geophone arrays (BS and RR) were deployed across the Clark segment of the San Jacinto Fault between Anza and Hemet during winter 2015 and Fall 2016, respectively. Both arrays were 2 km long with 20 m station spacing. Month-long three-component ambient seismic noise data were recorded and used to calculate multi-channel cross-correlation functions. All three-component noise records of each array were normalized simultaneously to retain relative amplitude information between different stations and different components. We observed clear Rayleigh waves and Love waves on the cross-correlations of both arrays at 0.3 - 1 s period. The phase travel times of the Rayleigh waves on both arrays were measured by frequency-time analysis (FTAN), and inverted for Rayleigh wave phase velocity profiles of the upper 500 m depth. For both arrays, we observe prominent asymmetric low velocity zones which narrow with depth. At the BS array near the Hemet Stepover, an approximately 250m wide slow zone is observed to be offset by 75m to the northeast of the surface fault trace. At the RR array near the Anza segment of the fault, a similar low velocity zone width and offset are observed, along with a 10% across-fault velocity contrast. Analyses of Rayleigh wave ellipticity (H/V ratio), Love wave phase travel times, and site amplification are in progress. By using multiple measurements from ambient noise cross-correlations, we can obtain strong constraints on the local damage zone structure of the San Jacinto Fault. The results contribute to improved understanding of rupture directivity, maximum earthquake magnitude and more generally seismic hazard associated with the San Jacinto fault zone.

  19. Mutagenic effects of sodium azide and γ-irradiation in Pisum

    International Nuclear Information System (INIS)

    Sander, C.; Muehlbauer, F.J.

    1977-01-01

    Sodium azide was an effective mutagen in Pisum when used at a concentration of 10 -3 M and at pH 3. Effects on dry, sound seeds of 'Juneau' so treated for 3 or 4 hr and for 3 hr in the presence of oxygen were compared with responses to 5, 10 and 20 kR of γ-rays for evaluating relative effectiveness in producing mutants. Leaf aberrations were observed on γ-irradiated plants but not on azide-treated plants, an indication that azide did not cause chromosome damage. At the treatment levels used, sodium azide was as effective in total yield of mutants but produced fewer stunted and variously deformed plants than γ-rays. (author)

  20. 2-O-α-glucopytanosyl L-ascorbic acid reduced mutagenicity at HPRT locus of mouse splenocytes following BNCT

    International Nuclear Information System (INIS)

    Kinashi, Yuko; Masunaga, Shin-ichiro; Suzuki, Minoru; Nagata, Kanji; Ono, Koji

    2006-01-01

    In boron neutron capture therapy (BNCT), normal tissue surrounding the tumor cells sometimes take up boron compounds resulting in radiation-induced damage to normal tissue. We have previously reported the evidence for increased the mutagenicity of thermal neutron in the presence of boron. In addition, we described the biological radio-protective effects of the ascorbic acid for mutation induction following BNCT in vitro. Here, we investigated these radio-protective effects of ascorbic acid for mutation induction in mouse splenocytes on HPRT locus following a BNCT study in vivo. (author)

  1. Assessment of mutagenic, antimutagenic and genotoxicity effects of Mimosa tenuiflora

    Directory of Open Access Journals (Sweden)

    Viviane A. Silva

    2013-02-01

    Full Text Available Genotoxic effects of Mimosa tenuiflora (Willd. Poir, Fabaceae, were investigated by using both micronucleus test and bacterial reverse mutation assay in Salmonella typhimurium TA97, TA98, TA100, TA102 respectively. In respect of Ames test results show that the extract does not induce mutations in any strains of Salmonella typhimurium tested since the mutagenicity index is less than 2. In the antimutagenic effect was observed that the extract at the concentrations tested significantly decreased the mutagenicity index of all strains tested which characterized the extract as antimutagenic in these conditions. In the micronucleus test in vivo, we observed that the concentrations used did not induce an increase in the frequency of micronucleus in normochromatic erythrocytes of mice. Therefore, we concluded that the extract of M. tenuiflora is not mutagenic in the absence of exogenous metabolizing system and does not induce an increase in the frequency of the micronucleus characterized as an agent not mutagenic in these conditions. Further studies of toxicity need to be made to the use of this plant in the treatment of diseases to be stimulated.

  2. Assessment of mutagenic, antimutagenic and genotoxicity effects of Mimosa tenuiflora

    Directory of Open Access Journals (Sweden)

    Viviane A. Silva

    2013-04-01

    Full Text Available Genotoxic effects of Mimosa tenuiflora (Willd. Poir, Fabaceae, were investigated by using both micronucleus test and bacterial reverse mutation assay in Salmonella typhimurium TA97, TA98, TA100, TA102 respectively. In respect of Ames test results show that the extract does not induce mutations in any strains of Salmonella typhimurium tested since the mutagenicity index is less than 2. In the antimutagenic effect was observed that the extract at the concentrations tested significantly decreased the mutagenicity index of all strains tested which characterized the extract as antimutagenic in these conditions. In the micronucleus test in vivo, we observed that the concentrations used did not induce an increase in the frequency of micronucleus in normochromatic erythrocytes of mice. Therefore, we concluded that the extract of M. tenuiflora is not mutagenic in the absence of exogenous metabolizing system and does not induce an increase in the frequency of the micronucleus characterized as an agent not mutagenic in these conditions. Further studies of toxicity need to be made to the use of this plant in the treatment of diseases to be stimulated.

  3. Effectiveness and efficiency of chemical mutagens in cowpea (Vigna ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-11-19

    Nov 19, 2008 ... A study was undertaken in a cowpea (Vigna unguiculata (L.) Walp.) variety CO 6 to assess the efficiency and effectiveness of chemical mutagens; ethyl methane sulphonate (EMS), diethyl sulphate (DES) and sodium azide (SA). EMS treatments were found highly effective than the other chemicals.

  4. The molecular properties of nitrobenzanthrone isomers and their mutagenic activities.

    Science.gov (United States)

    Ostojić, Bojana D; Stanković, Branislav; Ðorđević, Dragana S

    2014-06-01

    The mutagenic activity of five mono-substituted nitrobenzanthrones (NBA) has been determined in the Ames assay (Takamura-Enya et al., 2006). In the present study, a theoretical investigation of the electronic properties of all mono-substituted NBA isomers and their relation to mutagenic activity are presented. Equilibrium geometries, vertical ionization potentials (VIP), vertical electron affinities (VEA), relative energies, dipole moments and electronic dipole polarizabilities, and the IR and Raman spectra of NBA isomers calculated by Density Functional Theory (DFT) methods are presented. The position of the nitro group affects the spectral features of the IR and Raman spectra of the NBA isomers. The results show that a good linear relationship exists between the summation of Raman activities (∑ARaman) over all the 3N-6 vibrational modes and the mutagenic activity of the NBA isomers in Salmonella typhimurium strains. The spectroscopic results suggest that the unknown mutagenic activities of 4-NBA, 5-NBA, 6-NBA, 8-NBA and 10-NBA are predicted to follow the order 4-NBA>10-NBA>5-NBA>8-NBA>6-NBA. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Micronuclei frequency in children exposed to environmental mutagens: a review

    DEFF Research Database (Denmark)

    Neri, Monica; Fucic, Aleksandra; Knudsen, Lisbeth E

    2003-01-01

    studies in children are a promising field, since because of evident differences in the uptake, metabolism, distribution and excretion of mutagens this population seems to be more susceptible than adults. Further, the effect of major confounders such as cigarettes smoking, occupation, life...

  6. Absence of Mutagenicity in Three Nigerian Medicinal Plants ...

    African Journals Online (AJOL)

    Erah

    of the medicinal plant trade in the region [2]. One of the basic criteria set by World Health. Organization (WHO) for the use of herbs as medicines is that they should be shown to be non-toxic [3,4]. Bacterial reverse mutation assay (Ames test) was used in this work to evaluate the mutagenic potential of the methanolic extracts ...

  7. (Anti)mutagenic and immunomodulatory properties of quercetin glycosides

    Czech Academy of Sciences Publication Activity Database

    Valentová, Kateřina; Šíma, Petr; Rybková, Z.; Křižan, Jiří; Malachová, K.; Křen, Vladimír

    2016-01-01

    Roč. 96, č. 5 (2016), s. 1492-1499 ISSN 0022-5142 R&D Projects: GA ČR(CZ) GAP301/11/0767; GA MŠk(CZ) LD14096 Institutional support: RVO:61388971 Keywords : quercetin glycosides * (anti)mutagenicity * mice Subject RIV: EE - Microbiology, Virology Impact factor: 2.463, year: 2016

  8. Genotoxicity and mutagenicity of solid waste leachates: A review

    African Journals Online (AJOL)

    user

    2013-07-03

    Jul 3, 2013 ... There is need for a shift from waste disposal to sustainable waste management. Awareness on possible health ... Key words: Solid waste leachate, genotoxicity, mutagenicity, environmental pollution. INTRODUCTION. Solid wastes .... landfills and incineration residues from Japan include persistent organic ...

  9. Mutagenic and antimutagenic potentials of fruit juices of five ...

    African Journals Online (AJOL)

    Mutagenic and antimutagenic activities of freeze dried fruit juices (FDFJ) of Morinda elliptica Ridl. (Rubiaceae), Morinda citrifolia L. (Rubiaceae), Averrhoa bilimbi L. (Oxalidaceae), Phyllantus acidus (L.) Skeels (Phyllantaceae) and Myristica fragrans Houtt. (Myristicaceae) in Allium cepa L was evaluated. Testing the ...

  10. 28. Annual Meeting of the European Environmental Mutagen Society

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-09-01

    The 28{sup th} Annual Meeting of the European Environmental Mutagen Society took place in Salzburg from September 7{sup th} till September 11{sup th}, 1998. A lot of presentations also dealt with many radiation effects on cells, chromosomal aberrations and genetic effects caused by radioactive irradiation. In vivo and in vitro experiments concerning radiation injuries and carcinomas are analyzed. (Cecil)

  11. 28. Annual Meeting of the European Environmental Mutagen Society

    International Nuclear Information System (INIS)

    1998-09-01

    The 28 th Annual Meeting of the European Environmental Mutagen Society took place in Salzburg from September 7 th till September 11 th , 1998. A lot of presentations also dealt with many radiation effects on cells, chromosomal aberrations and genetic effects caused by radioactive irradiation. In vivo and in vitro experiments concerning radiation injuries and carcinomas are analyzed. (Cecil)

  12. Mutagenicity and chemical characterization of two petroleum distillates.

    Science.gov (United States)

    Carver, J H; MacGregor, J A; King, R W

    1984-08-01

    To investigate if the Salmonella/microsome assay could reliably screen complex petroleum samples for their carcinogenic potential, two high boiling (700-1070 degrees F) petroleum distillates with known activity in a dermal carcinogenesis bioassay were fully characterized with respect to their hydrocarbon composition and polynuclear aromatic hydrocarbon (PNA) content and assayed for mutagenic activity. Mutagenicity assays were also carried out on the aromatic hydrocarbon aggregates separated from these oils by adsorption chromatography. The composition of the distillates differed substantially, and reflected the fact that they were derived from crude oils that were extremely divergent in hydrocarbon character. Both the distillate and aromatic samples consistently induced a very slight increase in revertant TA98 and TA100 colonies; however, an increase of 2-4-fold over background was observed when the S-9 concentration was increased 5-10 times that of the standard assay. The maximal response was less than that expected from the samples' known PNA content and observed potency in the dermal carcinogenesis bioassay. In the Salmonella/microsome assay, all samples inhibited the mutagenic activity of added benzo[a]pyrene. Discordance between the magnitude of the samples' mutagenic activity and their known PNA content may be related to direct or indirect inhibition of sample PNAs by other components of the complex petroleum fractions. Observed inhibitory effects support the use of elevated S-9 concentration in the in vitro assays assessing the carcinogenic potential of petroleum-derived materials.

  13. MUTAGEN: Multi-user tool for annotating GENomes

    DEFF Research Database (Denmark)

    Brugger, K.; Redder, P.; Skovgaard, Marie

    2003-01-01

    MUTAGEN is a free prokaryotic annotation system. It offers the advantages of genome comparison, graphical sequence browsers, search facilities and open-source for user-specific adjustments. The web-interface allows several users to access the system from standard desktop computers. The Sulfolobus...

  14. Mutagenic effects of alkylating agents on prophage lambda

    Energy Technology Data Exchange (ETDEWEB)

    Bresler, S.; Kalinin, V.L.; Kuznetsova, L.V.

    1984-06-01

    An evaluation was made of the relative contribution of repair and reparative mechanisms to the mutagenic potency of several alkylating agents on thermoinducible prophage lambdacI857 ind/sup -/ in several stains of E. coli. Following treatment of lysogenic E. coli with the mutagens and heat induction, 0.02 N-nitroso-N-methylurea (NMU) induced c mutations with a high frequency (ca. 10%) in both wild type E. coli and cells with repair mutations (recA13, lexA102, uvrA6, umuC36, xthA9, recF143, polA1, uvrD3, uvrD502). It appears that NUM-induced mutations are stabilized as replicative errors due to mismatched, altered bases. Delay in induction following exposure to NMU improves prophage survival and diminishes c mutant formation, regardless of the E. coli genotype. Evidently, carbamoylation is not involved in NMU mutagenicity since 0.02 M KNCO is nonmutagenic and is virtually without effect on prophage viability. Replicative mechanisms are also involved in N-methyl-N'-nitro-N-nitrosoguanidine (15%) and ethyl methanesulfonate (2%) induced mutations, since the maximum yield of mutants was independent of recA/sup +/ genotype. However, the mutagenicity of methyl methanesulfonate was abolished by the recA mutation, indicating that the mutagenicity of this agent is repair-dependent. Mitomycin C (0.1%) and acridine mustard (0.3%) induce c mutations regardless of recA/sup +/ and, therefore, appear to do so by intercalation. 26 references, 6 figures.

  15. Balancing repair and tolerance of DNA damage caused by alkylating agents

    OpenAIRE

    Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D.

    2012-01-01

    Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial ...

  16. SERIES: Genomic instability in cancer Balancing repair and tolerance of DNA damage caused by alkylating agents

    OpenAIRE

    Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D

    2012-01-01

    Alkylating agents comprise a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER), and mismatch repair (MMR) respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial fo...

  17. RFWD3-Mediated Ubiquitination Promotes Timely Removal of Both RPA and RAD51 from DNA Damage Sites to Facilitate Homologous Recombination.

    Science.gov (United States)

    Inano, Shojiro; Sato, Koichi; Katsuki, Yoko; Kobayashi, Wataru; Tanaka, Hiroki; Nakajima, Kazuhiro; Nakada, Shinichiro; Miyoshi, Hiroyuki; Knies, Kerstin; Takaori-Kondo, Akifumi; Schindler, Detlev; Ishiai, Masamichi; Kurumizaka, Hitoshi; Takata, Minoru

    2017-06-01

    RFWD3 is a recently identified Fanconi anemia protein FANCW whose E3 ligase activity toward RPA is essential in homologous recombination (HR) repair. However, how RPA ubiquitination promotes HR remained unknown. Here, we identified RAD51, the central HR protein, as another target of RFWD3. We show that RFWD3 polyubiquitinates both RPA and RAD51 in vitro and in vivo. Phosphorylation by ATR and ATM kinases is required for this activity in vivo. RFWD3 inhibits persistent mitomycin C (MMC)-induced RAD51 and RPA foci by promoting VCP/p97-mediated protein dynamics and subsequent degradation. Furthermore, MMC-induced chromatin loading of MCM8 and RAD54 is defective in cells with inactivated RFWD3 or expressing a ubiquitination-deficient mutant RAD51. Collectively, our data reveal a mechanism that facilitates timely removal of RPA and RAD51 from DNA damage sites, which is crucial for progression to the late-phase HR and suppression of the FA phenotype. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Characterisation of Beaver Habitat Parameters That Promote the Use of Culverts as Dam Construction Sites: Can We Limit the Damage to Forest Roads?

    Directory of Open Access Journals (Sweden)

    Geneviève Tremblay

    2017-12-01

    Full Text Available The use of forest roads as foundations for dam construction by beavers is a recurrent problem in the management of forest road networks. In order to limit the damage to forest roads, our goal was to calculate the probability of beaver dam installation on culverts, according to surrounding habitat parameters, which could allow for improvement in the spatial design of new roads that minimise conflicts with beavers. Comparisons of culverts with (n = 77 and without (n = 51 dams in northwestern Quebec showed that catchment surface, cumulate length of all local streams within a 2-km radius, and road embankment height had a negative effect on the probability of dam construction on culverts, while flow level and culvert diameter ratio had a positive effect. Nevertheless, predicted probabilities of dam construction on culverts generally exceeded 50%, even on sites that were less favourable to beavers. We suggest that it would be more reasonable to take their probable subsequent presence into account at the earliest steps of road conception. Installing mitigation measures such as pre-dams during road construction would probably reduce the occurrence of conflicts with beavers and thus reduce the maintenance costs of forest roads.

  19. Mosquito breeding sites and People’s knowledge of mosquitoes and mosquito borne diseases: A comparison of temporary housing and non-damaged village areas in Sri Lanka after the tsunami strike in 2004

    OpenAIRE

    Ohba, Shin-ya; Kashima, Saori; Matsubara, Hiromi; Higa, Yukiko; Piyaseeli, Udage Kankanamge D.; Yamamoto, Hideki; Nakasuji, Fusao

    2010-01-01

    Although it is very important in view of public health to understand the mosquito breeding sites and key reservoirs existing around residential areas, such information is lacking in temporary housing sites constructed after the serious tsunami strikes on 26 December 2004 in Sri Lanka. This study clarified the situation regarding mosquito breeding 14 months after the tsunami in Sri Lanka by surveying temporary housing and non-damaged village areas, and also by examining people‘s knowledge rela...

  20. Non-random alkylation of DNA sequences induced in vivo by chemical mutagens

    Energy Technology Data Exchange (ETDEWEB)

    Durante, M.; Geri, C.; Bonatti, S.; Parenti, R. (Universita di Pisa (Italy))

    1989-08-01

    Previous studies of the interaction of alkylating agents on the eukaryotic genome support the idea that induction of DNA adducts is at specific genomic sites. Here we show molecular and cytological evidence that alkylation is rather specific. Mammalian cell cultures were exposed to different doses of mutagens and the DNA was analyzed by density gradient ultracentrifugation, hydroxylapatite fractionation, and by restriction enzyme analysis. Studies with the labelled mutagens N-ethyl-N-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine show that there is a non-random distribution of the adducts. The adducts are found more frequently in A-T, G-C rich satellite DNA and highly repetitive sequences. Analysis with restriction enzymes shows that both methyl and ethyl groups influence the restriction patterns of the enzymes HpaII and MspI that recognize specific endogenous DNA methylation. These data suggest, as a subsequent mechanism, a modification in the pattern of the normal endogenous methylation of 5-methylcytosine.

  1. Mutagenic hazards of complex polycyclic aromatic hydrocarbon mixtures in contaminated soil

    Energy Technology Data Exchange (ETDEWEB)

    Lemieux, C.L.; Lambert, A.B.; Lundstedt, S.; Tysklind, M.; White, P.A. [Health Canada, Ottawa, ON (Canada). Safe Environment Program

    2008-04-15

    The objective of the present study was to evaluate hazard/risk assessment methods for complex environmental mixtures that involve a targeted, priority chemical approach based on the cumulative hazard/risk of known mixture components or analyses of sufficiently similar mixtures. Ten polycyclic aromatic hydrocarbon (PAH)-contaminated soils were separated into nonpolar and semipolar fractions, and both fractions elicited positive responses on the Salmonella reverse mutation assay. Targeted and nontargeted methods of hazard prediction routinely overestimated mutagenic activities for the nonpolar soil fractions, suggesting nonadditive interactions of PAHs in complex mixtures. This suggests that current risk assessment methods for complex mixtures may provide conservative estimates regarding soils contaminated with priority PAHs alone. Significant underestimations of total risk, however, will be obtained if the soils also contain unidentified PAHs as well as polycyclic aromatic compounds and related compounds that contribute to the total mutagenic activity. Furthermore, estimates of excess lifetime cancer risk associated with the nondietary ingestion of the PAH-contaminated soils studied here indicate that a traditional risk assessment model based on identified priority PAHs and an assumption of additivity generally underestimates the risk associated with the nonpolar soil fractions (in comparison to bioassay-derived risk estimates). Additional cancer risk may be associated with the more polar compounds that also are found at these contaminated sites and that rarely are included in the standard risk assessment methodology.

  2. Genotoxicity and mutagenicity of Echinodorus macrophyllus (chapéu-de-couro extracts

    Directory of Open Access Journals (Sweden)

    Leonardo S. Vidal

    2010-01-01

    Full Text Available Echinodorus macrophyllus, commonly known as chapéu-de-couro, is a medicinal plant used in folk medicine to treat inflammation and rheumatic diseases. In this work, we used short-term bacterial assays based on the induction of SOS functions to examine the genotoxicity and mutagenicity of an aqueous extract of E. macrophyllus leaves. Whole extract and an ethyl acetate fraction showed similar genotoxicity and caused an ~70-fold increase in lysogenic induction. The extract also gave a positive result in the SOS chromotest with an increase of 12-fold in β-Galactosidase enzymatic units. There was a strong trend towards base substitutions and frameshifts at purine sites in the mutations induced by the extract in Escherichia coli (CC103 and CC104 strains and Salmonella typhimurium test strains (22-fold increase in histidine revertants in TA98 strain. Since reactive oxygen species may be implicated in aging process and in degenerative diseases, we used antioxidant compounds as catalase, thiourea and dipyridyl in the lysogenic induction test. All this compounds were able to reduce the induction factor observed in the treatment with chapéu-de-couro, thus suggesting that the genotoxicity and mutagenicity were attributable to the production of reactive oxygen species that targeted DNA purines.

  3. Assessment of the Mutagenicity of Sediments from Yangtze River Estuary Using Salmonella Typhimurium/Microsome Assay

    Science.gov (United States)

    Liu, Li; Chen, Ling; Floehr, Tilman; Xiao, Hongxia; Bluhm, Kerstin; Hollert, Henner; Wu, Lingling

    2015-01-01

    Sediments in estuaries are of important environmental concern because they may act as pollution sinks and sources to the overlying water body. These sediments can be accumulated by benthic organisms. This study assessed the mutagenic potential of sediment extracts from the Yangtze River estuary by using the Ames fluctuation assay with the Salmonella typhimurium his (−) strain TA98 (frameshift mutagen indicator) and TA100 (baseshift mutagen indicator). Most of the sediment samples were mutagenic to the strain TA98, regardless of the presence or absence of exogenous metabolic activation (S9 induction by β-naphthoflavone/phenobarbital). However, none of the samples were mutagenic to the strain TA100. Thus, the mutagenicity pattern was mainly frameshift mutation, and the responsible toxicants were both direct (without S9 mix) and indirect (with S9 mix) mutagens. The mutagenicity of the sediment extracts increased when S9 was added. Chemical analysis showed a poor correlation between the content of priority polycyclic aromatic hydrocarbons and the detected mutagenicity in each sample. The concept of effect-directed analysis was used to analyze possible compounds responsible for the detected mutagenic effects. With regard to the mutagenicity of sediment fractions, non-polar compounds as well as weakly and moderately polar compounds played a main role. Further investigations should be conducted to identify the responsible components. PMID:26606056

  4. Computational studies of radiation and oxidative damage to DNA and its recognition by repair enzyme

    Energy Technology Data Exchange (ETDEWEB)

    Pinak, M. [Center for Promotion of Computational Science and Engineering, Tokai Research Establishment, Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan)

    2000-03-01

    Molecular dynamics (MD) simulation is used to study the time evolution of the recognition processes and to construct a model of the specific DNA-repair enzyme' complexes. MD simulations of the following molecules were performed: DNA dodecamer with thymine dimer (TD), DNA 30-mer with thymine glycol (TG), and respective specific repair enzymes T4 Endonuclease V and Endonuclease III. Both DNA lesions are experimentally suggested to be mutagenic and carcinogenic unless properly recognized and repaired by repair enzymes. In the case of TD, there is detected a strong kink around the TD site, that is not observed in native DNA. In addition there is observed a different value of electrostatic energy at the TD site - negative '-9 kcal/mol', in contrast to the nearly neutral value of the native thymine site. These two factors - structural changes and specific electrostatic energy - seem to be important for proper recognition of a TD damaged site and for formation of DNA-enzyme complex. Formation of this complex is the onset of the repair of DNA. In the case of TG damaged DNA the structural characteristics of the TG were calculated (charges, bond lengths, bond angles, etc.). The formed TG was used to replace the native thymine and then submitted to the simulation in the system with a repair enzyme with Endonuclease III for the purpose of the study of the formation of the DNA-enzyme complex. (author)

  5. Molecular basis for the mutagenic and lethal effects of ultraviolet irradiation. Research accomplishments (1968 to present)

    International Nuclear Information System (INIS)

    Grossman, L.

    1978-01-01

    Earlier work on the chemical basis of mutagenesis led to certain chemical generalities sufficient to explain how certain mutagens such as uv light and hydroxylamine functioned in information transfer systems (replicative, transcriptive and translational). When such modifications were applied to biologically active DNA in a controlled manner biological expression was non-stoichiometric because much of the damage was removed from the DNA by repair systems. Our efforts were then directed to these systems which led to: (1) the isolation, purification and characterization of endonucleases responsible for the first and controlling step in DNA repair - referred to as incision in both M. luteus and E. coli. The biological role of these enzymes was inferred in appropriate mutants; (2) the isolation, purification and characterization of exonucleases responsible for the removal or excision of damaged nucleotides in M. luteus and human placental trophoblasts; (3) the repair of uv damaged biologically active transforming and transfecting DNAs by purified endonucleases, exonucleases, DNA polymerase I and polynucleotide ligase from M. luteus and E. coli; (4) the characterization of the dual gene control for incision phenomenon in M. luteus and E. coli; and (5) isolation, purification and characterization of repair enzymes from human placenta

  6. Mutagenic activity of halogenated propanes and propenes: effect of bromine and chlorine positioning.

    Science.gov (United States)

    Låg, M; Omichinski, J G; Dybing, E; Nelson, S D; Søderlund, E J

    1994-10-01

    A series of halogenated propanes and propenes were studied for mutagenic effects in Salmonella typhimurium TA100 in the absence or presence of NADPH plus liver microsomes from phenobarbital-induced rats as an exogenous metabolism system. The cytotoxic and mutagenic effects of the halogenated propane 1,2-dibromo-3-chloropropane (DBCP) has previously been studied in our laboratories. These studies showed that metabolic activation of DBCP was required to exert its detrimental effects. All of the trihalogenated propane analogues were mutagenic when the microsomal activation system was included. The highest mutagenic activity was obtained with 1,2,3-tribromopropane, with approximately 50-fold higher activity than the least mutagenic trihalogenated propane, 1,2,3-trichloropropane. The order of mutagenicity was as follows: 1,2,3-tribromopropane > or = 1,2-dibromo- 3-chloropropane > 1,3-dibromo-2-chloropropane > or = 1,3-dichloro-2-bromopropane > 1-bromo-2,3-dichloropropane > 1,2,3-trichloropropane. Compared to DBCP, the dihalogenated propanes were substantially less mutagenic. Only 1,2-dibromopropane was mutagenic and its mutagenic potential was approximately 1/30 of that of DBCP. In contrast to DBCP, 1,2-dibromopropane showed similar mutagenic activity with and without the addition of an activation system. The halogenated propenes 2,3-dibromopropene and 2-bromo-3-chloropropene were mutagenic to the bacteria both in the absence and presence of the activation system, whereas 2,3-dichloropropene did not show any mutagenic effect. The large differences in mutagenic potential between the various halogenated propanes and propenes are proposed to be due to the formation of different possible proximate and ultimate mutagenic metabolites resulting from the microsomal metabolism of the various halogenated propanes and propenes, and to differences in the rate of formation of the metabolites. Pathways are proposed for the formation of genotoxic metabolites of di- and trihalogenated

  7. Identification of the Dimer Exchange Interface of the Bacterial DNA Damage Response Protein UmuD.

    Science.gov (United States)

    Murison, David A; Timson, Rebecca C; Koleva, Bilyana N; Ordazzo, Michael; Beuning, Penny J

    2017-09-12

    The Escherichia coli SOS response, an induced DNA damage response pathway, confers survival on bacterial cells by providing accurate repair mechanisms as well as the potentially mutagenic pathway translesion synthesis (TLS). The umuD gene products are upregulated after DNA damage and play roles in both nonmutagenic and mutagenic aspects of the SOS response. Full-length UmuD is expressed as a homodimer of 139-amino-acid subunits, which eventually cleaves its N-terminal 24 amino acids to form UmuD'. The cleavage product UmuD' and UmuC form the Y-family polymerase DNA Pol V (UmuD' 2 C) capable of performing TLS. UmuD and UmuD' exist as homodimers, but their subunits can readily exchange to form UmuDD' heterodimers preferentially. Heterodimer formation is an essential step in the degradation pathway of UmuD'. The recognition sequence for ClpXP protease is located within the first 24 amino acids of full-length UmuD, and the partner of full-length UmuD, whether UmuD or UmuD', is degraded by ClpXP. To better understand the mechanism by which UmuD subunits exchange, we measured the kinetics of exchange of a number of fluorescently labeled single-cysteine UmuD variants as detected by Förster resonance energy transfer. Labeling sites near the dimer interface correlate with increased rates of exchange, indicating that weakening the dimer interface facilitates exchange, whereas labeling sites on the exterior decrease the rate of exchange. In most but not all cases, homodimer and heterodimer exchange exhibit similar rates, indicating that somewhat different molecular surfaces mediate homodimer exchange and heterodimer formation.

  8. Effect of process distillation on mutagenicity and cell-transformation activity of solvent-refined, coal-derived liquids

    Energy Technology Data Exchange (ETDEWEB)

    Pelroy, R.A.; Frazier, M.E.; Later, D.W.; Wright, C.W.; Wilson, B.W.

    1985-05-01

    Blended SRC-II process streams, representing a full boiling range distillate material, were fractionally distilled into non-overlapping 50 F cuts with bp between 300 and 850 C and another set with bp ranging between 138 and 1055 F. Distillate cuts were assayed for mutagenic activity using the histidine reversion assay with Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537, as well as for mammalian-cell transformation (mct) activity in the Syrian hamster embryo test, and DNA damage in the prophage induction assay (pia). Samples were also separated into chemical class fractions by alumina column chromatography and analysed by high resolution gas chromatography. In the met and microbial mutagenicity assays, significant activity was found almost exclusively in cuts with bp> above 700 F, with the highest activity in the mct assay observed for cuts above 800 F. All of the cuts showed increased levels of DNA damage as expressed by lambda pia in Escherichia coli 8177. However, the greatest activity was associated with cuts with bp in the 800 F+ range. Chemical analysis of the 50 F cuts showed a variety of polycyclic aromatic hydrocarbons (PAH) and amino-PAH compounds to be present in the cuts with bp> above 700 F and essentially absent from cuts with bp< 700 F. The sample set of non-overlapping (50 F) cuts were reblended according to the proportions of each cut found in the original blend material. These reblended composites were then assayed to compare their activity with that predicted from the activities of the component cuts. The results indicated the microbial mutagenicity response was essentially additive. Met activities were non-additive, indicating a compositional effect on the expression of transforming agents in the complex mixture. 18 references.

  9. An immunochemical approach to the study of DNA damage and repair

    International Nuclear Information System (INIS)

    Wallace, S.S.; Erlanger, B.F.

    1992-05-01

    The overall objective of this project has been to develop immunochemical methods to quantitate unique DNA base damages in order to facilitate studies on radiation-induced damage production and repair. Specifically, we have been using antibodies raised to damaged bases to quantitate unique lesions in model systems in order to evaluate their potential biological consequences. Our approach has been to synthesize modified nucleotides or nucleosides, conjugate them to protein carriers, and use the conjugates as immunogens in rabbits or to prepare monoclonal antibodies. We have been studying damages that are stable radiolysis products found in X-irradiated DNA and thus of potential biological consequence. Our aim is to build an in vitro and in vivo data base on the interactions between model DNA lesions and such cellular enzymes as DNA polymerases and repair endonucleases. Initial studies have focused on pyrimidine ring saturation products (thymine glycol.and dihydrothymine), products resulting from ring fragmentation or base loss (urea, Β-ureidoisobutyric acid, abasic sites), 7-hydro-8-oxopurines, and more recently, cytosine radiolysis products. These modified bases serve as useful models for examining the potential lethal and/or mutagenic (carcinogenic) effects of the products of DNA radiolysis

  10. Reduction of hexavalent chromium by fasted and fed human gastric fluid. I. Chemical reduction and mitigation of mutagenicity

    Energy Technology Data Exchange (ETDEWEB)

    De Flora, Silvio, E-mail: sdf@unige.it [Department of Health Sciences, University of Genoa, 16132 Genoa (Italy); Camoirano, Anna, E-mail: Anna.Fiorenza.Camoirano@unige.it [Department of Health Sciences, University of Genoa, 16132 Genoa (Italy); Micale, Rosanna T., E-mail: rosannamicale@yahoo.it [Department of Health Sciences, University of Genoa, 16132 Genoa (Italy); La Maestra, Sebastiano, E-mail: lamaestra78@yahoo.it [Department of Health Sciences, University of Genoa, 16132 Genoa (Italy); Savarino, Vincenzo, E-mail: vsavarin@unige.it [Gastroenterology Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa (Italy); Zentilin, Patrizia, E-mail: Patrizia.Zentilin@unige.it [Gastroenterology Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa (Italy); Marabotto, Elisa, E-mail: emarabotto@libero.it [Gastroenterology Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa (Italy); Suh, Mina, E-mail: msuh@toxstrategies.com [ToxStrategies, Mission Viejo, CA 92692 (United States); Proctor, Deborah M., E-mail: dproctor@toxstrategies.com [ToxStrategies, Mission Viejo, CA 92692 (United States)

    2016-09-01

    Evaluation of the reducing capacity of human gastric fluid from healthy individuals, under fasted and fed conditions, is critical for assessing the cancer hazard posed by ingested hexavalent chromium [Cr(VI)] and for developing quantitative physiologically-based pharmacokinetic models used in risk assessment. In the present study, the patterns of Cr(VI) reduction were evaluated in 16 paired pre- and post-meal gastric fluid samples collected from 8 healthy volunteers. Human gastric fluid was effective both in reducing Cr(VI), as measured by using the s-diphenylcarbazide colorimetric method, and in attenuating mutagenicity in the Ames test. The mean (± SE) Cr(VI)-reducing ability of post-meal samples (20.4 ± 2.6 μg Cr(VI)/mL gastric fluid) was significantly higher than that of pre-meal samples (10.2 ± 2.3 μg Cr(VI)/mL gastric fluid). When using the mutagenicity assay, the decrease of mutagenicity produced by pre-meal and post-meal samples corresponded to reduction of 13.3 ± 1.9 and 25.6 ± 2.8 μg Cr(VI)/mL gastric fluid, respectively. These data are comparable to parallel results conducted by using speciated isotope dilution mass spectrometry. Cr(VI) reduction was rapid, with > 70% of total reduction occurring within 1 min and 98% of reduction is achieved within 30 min with post-meal gastric fluid at pH 2.0. pH dependence was observed with decreasing Cr(VI) reducing capacity at higher pH. Attenuation of the mutagenic response is consistent with the lack of DNA damage observed in the gastrointestinal tract of rodents following administration of ≤ 180 ppm Cr(VI) for up to 90 days in drinking water. Quantifying Cr(VI) reduction kinetics in the human gastrointestinal tract is necessary for assessing the potential hazards posed by Cr(VI) in drinking water. - Highlights: • Cr(VI) reduction capacity was greater in post-meal than paired pre-meal samples. • Cr(VI) reduction was rapid, pH dependent, and due to heat stable components. • Gastric fluid attenuates

  11. Sensitivity to ehter anasthesia and to γ-rays in mutagen-sensitive strains of Drosophila melanogaster

    International Nuclear Information System (INIS)

    Gamo, Sumiko; Nakashima-Tanaka, Eiji; Megumi, Tsuneo

    1990-01-01

    An ether-resistant strain of Drosophila melanogaster, Eth-29, has previously been found to be radiosensitive. Some mutagen-sensitive strains are known to be hypersensitive to X-rays in larvae. The correlation between sensitivities to ether anesthesia and to γ-rays was examined in adult flies of 12 mutagen-sensitive strains and 6 control strains. A wide variation in sensitivities to ether anesthesia, γ-ray knock-down and γ-ray lethality was demonstrated. No correlation between DNA-repaor capacity and ether sensitivity or γ-ray knock-down sensitivity was shown. Only mei-9 and mus201, which are deficient in excision repair, as well as Eth-29 were found to be sensitive to γ-ray lethality. These findings indicate that the targets for ehter anesthesia, knock-down and lethality may be different. Lethality appears to be caused by DNA damage, while the othe 2 endpoints appear not to be related to DNA damage. (author). 14 refs.; 3 tabs

  12. Characterization of urban aerosol: seasonal variation of mutagenicity and genotoxicity of PM2.5, PM1 and semi-volatile organic compounds.

    Science.gov (United States)

    Bocchi, Clara; Bazzini, Cristina; Fontana, Federica; Pinto, Giancarlo; Martino, Anna; Cassoni, Francesca

    2016-10-01

    Urban particulate matter (PM) is an environmental public health concern as it has been classified by the IARC as carcinogenic to humans (group 1) and it's well known that pollutants are more associated with the finest fractions of PM. In this study we characterize urban aerosol in Bologna, county town of Emilia-Romagna in the north of Italy, collecting PM 2.5 , PM 1 and semi-volatile organic compounds using polyurethane foam. Samples were collected in three different seasons (winter, summer and autumn) and were extracted with acetone. On these three fractions we assessed mutagenicity using Salmonella reverse mutation test and genotoxicity by alkaline comet assay and micronucleus assay in human lung cancer cell line, A549. Organic extracts were also characterized for alkanes, polycyclic aromatic hydrocarbons (PAHs), nitrated and oxygenated PAHs. We also evaluated associations between the physicochemical parameters of samples and their genotoxicity. The particulate samples, collected in autumn and winter, indicated the presence of both base pair substitution and frameshift mutagens using TA98 and TA100 strains of Salmonella typhimurium and the mutagenicity was more associated with the finest fraction. Enhanced mutagenic response was observed in the absence of enzyme activation. Only a third of comet and a half of micronucleus assays gave positive results that, unlike Salmonella's ones, are not season-related. These results were compared with environmental chemicals concentrations and we found that Salmonella's data correlated with PAHs detected on PM filters and with mass concentrations, whereas the DNA damage correlate only with PAHs extracted from polyurethane foams. The use of different assays was sensitive to detect and identify different classes of airborne mutagenic/genotoxic compounds present in aerosol, showing that monitoring air quality using this methodology is relevant. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Cloning of Salmonella typhimurium DNA encoding mutagenic DNA repair

    International Nuclear Information System (INIS)

    Thomas, S.M.; Sedgwick, S.G.

    1989-01-01

    Mutagenic DNA repair in Escherichia coli is encoded by the umuDC operon. Salmonella typhimurium DNA which has homology with E. coli umuC and is able to complement E. coli umuC122::Tn5 and umuC36 mutations has been cloned. Complementation of umuD44 mutants and hybridization with E. coli umuD also occurred, but these activities were much weaker than with umuC. Restriction enzyme mapping indicated that the composition of the cloned fragment is different from the E. coli umuDC operon. Therefore, a umu-like function of S. typhimurium has been found; the phenotype of this function is weaker than that of its E. coli counterpart, which is consistent with the weak mutagenic response of S. typhimurium to UV compared with the response in E. coli

  14. Pollen genetic markers for detection of mutagens in the environment

    International Nuclear Information System (INIS)

    Nilan, R.A.; Rosichan, J.L.; Arenaz, P.; Hodgdon, A.L.; Kleinhofs, A.

    1980-01-01

    To utilize and exploit pollen for in situ mutagen monitoring, screening and toxicology, the range of genetic traits in pollen must be identified and analyzed. To be useful for the development of mutagen detection systems proteins should be: (1) activity stainable or immunologically identifiable in the pollen, (2) the products of one to three loci; and (3) gametophytic and nuclear in origin. Several proteins, including alcohol dehydrogenase in maize, which meet these criteria are discussed. The waxy locus in barley and maize which controls starch deposition for pollen screening and mutant detection. Thirty waxy mutant lines, induced by sodium azide and gamma-rays are characterized for spontaneous and induced reversion frequencies, allelism, karyotype, amylose content, and UDPglucose glucosyltransferase (waxy gene product) activity. Twelve mutant alleles are being mapped by recombinant frequencies

  15. The resistance of Micrococcus radiodurans to killing and mutation by agents which damage DNA

    International Nuclear Information System (INIS)

    Sweet, D.M.; Moseley, B.E.B.

    1976-01-01

    The resistance of Micrococcus radiodurans to the lethal and mutagenic action of ultraviolet (UV) light, ionising (γ) radiation, mitomycin C (MTC), nitrous acid (NA), hydroxylamine (HA), N-methyl-N'-nitro-N-nitrosoguanidine (NG), ethylmethanesulphonate (EMS) and β-propiolactone (βPL) has been compared with that of Escherichia coli B/r. M. radiodurans was much more resistant than E. coli B/r to the lethal effects of UV light (by a factor of 33), γ-radiation (55), NG (15) and NA (62), showed intermediate resistance to MTC (4) and HA (7), but was sensitive to EMS (1) and βPL (2). M. radiodurans was very resistant to mutagens producing damage which can be repaired by a recombination system, indicating that it possesses an extremely efficient recombination repair mechanism. Both species were equally sensitive to mutation to trimethoprim resistance by NG, but M. radiodurans was more resistant than E. coli B/r to the other mutagens tested, being non-mutable by UV light, γ-radiation, MTC and HA, and only slightly sensitive to mutation by NA, EMS, and βPL. The resistance of M. radiodurans to mutation by UV light, γ-radiation and MTC is consistent with an hypothesis that recombination repair in M. radiodurans is accurate since these mutagens may depend on an 'error-prone' recombination system for their mutagenic effect in E. coli B/r. However, because M. radiodurans is also resistant to mutagens such as HA and EMS, which are mutagenic in E. coli in the absence of an 'error-prone' system, we propose that all the mutagens tested may have a common mode of action in E. coli B/r, but that this mutagenic pathway is missing in M. radiodurans

  16. Resistance of Micrococcus radiodurans to killing and mutation by agents which damage DNA

    Energy Technology Data Exchange (ETDEWEB)

    Sweet, D M; Moseley, B E.B. [Edinburgh Univ. (UK). School of Agriculture

    1976-02-01

    The resistance of Micrococcus radiodurans to the lethal and mutagenic action of ultraviolet (UV) light, ionising (..gamma..) radiation, mitomycin C (MTC), nitrous acid (NA), hydroxylamine (HA), N-methyl-N'-nitro-N-nitrosoguanidine (NG), ethylmethanesulphonate (EMS) and ..beta..-propiolactone (..beta..PL) has been compared with that of Escherichia coli B/r. M. radiodurans was much more resistant than E. coli B/r to the lethal effects of UV light (by a factor of 33), ..gamma..-radiation (55), NG (15) and NA (62), showed intermediate resistance to MTC (4) and HA (7), but was sensitive to EMS (1) and ..beta..PL (2). M. radiodurans was very resistant to mutagens producing damage which can be repaired by a recombination system, indicating that it possesses an extremely efficient recombination repair mechanism. Both species were equally sensitive to mutation to trimethoprim resistance by NG, but M. radiodurans was more resistant than E. coli B/r to the other mutagens tested, being non-mutable by UV light, ..gamma..-radiation, MTC and HA, and only slightly sensitive to mutation by NA, EMS, and ..beta..PL. The resistance of M. radiodurans to mutation by UV light, ..gamma.. radiation and MTC is consistent with an hypothesis that recombination repair in M. radiodurans is accurate since these mutagens may depend on an 'error-prone' recombination system for their mutagenic effect in E. coli B/r. However, because M. radiodurans is also resistant to mutagens such as HA and EMS, which are mutagenic in E. coli in the absence of an 'error-prone' system, we propose that all the mutagens tested may have a common mode of action in E. coli B/r, but that this mutagenic pathway is missing in M. radiodurans.

  17. Estimated airborne release of plutonium from Atomics International's Nuclear Materials Development Facility in the Santa Susana site, California, as a result of postulated damage from severe wind and earthquake hazard

    International Nuclear Information System (INIS)

    Mishima, J.; Ayer, J.E.

    1981-09-01

    The potential mass of airborne releases of plutonium (source term) that could result from wind and seismic damage is estimated for the Atomics International Company's Nuclear Materials Development Facility (NMDF) at the Santa Susana site in California. The postulated source terms will be useful as the basis for estimating the potential dose to the maximum exposed individual by inhalation and to the total population living within a prescribed radius of the site. The respirable fraction of airborne particles is thus the principal concern. The estimated source terms are based on the damage ratio, and the potential airborne releases if all enclosures suffer particular levels of damage. In an attempt to provide a realistic range of potential source terms that include most of the normal processing conditions, a best estimate bounded by upper and lower limits is provided. The range of source terms is calculated by combining a high best estimate and a low damage ratio, based on a fraction of enclosures suffering crush or perforation, with the airborne release from enclosures based upon an upper limit, average, and lower limit inventory of dispersible materials at risk. Two throughput levels are considered. The factors used to evaluate the fractional airborne release of materials and the exchange rates between enclosed and exterior atmospheres are discussed. The postulated damage and source terms are discussed for wind and earthquake hazard scenarios in order of their increasing severity

  18. Counteracting quasispecies adaptability: extinction of a ribavirin-resistant virus mutant by an alternative mutagenic treatment.

    Directory of Open Access Journals (Sweden)

    Celia Perales

    Full Text Available BACKGROUND: Lethal mutagenesis, or virus extinction promoted by mutagen-induced elevation of mutation rates of viruses, may meet with the problem of selection of mutagen-resistant variants, as extensively documented for standard, non-mutagenic antiviral inhibitors. Previously, we characterized a mutant of foot-and-mouth disease virus that included in its RNA-dependent RNA polymerase replacement M296I that decreased the sensitivity of the virus to the mutagenic nucleoside analogue ribavirin. METHODOLOGY AND PRINCIPAL FINDINGS: Replacement M296I in the viral polymerase impedes the extinction of the mutant foot-and-mouth disease virus by elevated concentrations of ribavirin. In contrast, wild type virus was extinguished by the same ribavirin treatment and, interestingly, no mutants resistant to ribavirin were selected from the wild type populations. Decreases of infectivity and viral load of the ribavirin-resistant M296I mutant were attained with a combination of the mutagen 5-fluorouracil and the non-mutagenic inhibitor guanidine hydrocloride. However, extinction was achieved with a sequential treatment, first with ribavirin, and then with a minimal dose of 5-fluorouracil in combination with guanidine hydrochloride. Both, wild type and ribavirin-resistant mutant M296I exhibited equal sensitivity to this combination, indicating that replacement M296I in the polymerase did not confer a significant cross-resistance to 5-fluorouracil. We discuss these results in relation to antiviral designs based on lethal mutagenesis. CONCLUSIONS: (i When dominant in the population, a mutation that confers partial resistance to a mutagenic agent can jeopardize virus extinction by elevated doses of the same mutagen. (ii A wild type virus, subjected to identical high mutagenic treatment, need not select a mutagen-resistant variant, and the population can be extinguished. (iii Extinction of the mutagen-resistant variant can be achieved by a sequential treatment of a

  19. Micronuclei frequency in children exposed to environmental mutagens: a review

    DEFF Research Database (Denmark)

    Neri, Monica; Fucic, Aleksandra; Knudsen, Lisbeth E

    2003-01-01

    Cytogenetic monitoring has been traditionally used for the surveillance of populations exposed to genotoxic agents. In recent years sensitivity problems emerged in surveys of populations exposed to low levels of mutagens, and therefore alternative approaches have been explored. Biomonitoring....... The limited number of published papers indicates that the conduct of properly designed studies on the effect of environmental pollutants in children may be difficult. This review confirmed the usefulness of MN assay in biomonitoring studies conducted in children, revealing that in many circumstances...

  20. Dietary Mutagen Exposure and Risk of Pancreatic Cancer

    OpenAIRE

    Li, Donghui; Sue Day, Rena; Bondy, Melissa L.; Sinha, Rashmi; Nguyen, Nga T.; Evans, Douglas B.; Abbruzzese, James L.; Hassan, Manal M.

    2007-01-01

    To investigate the association between dietary exposure to food mutagens and risk of pancreatic cancer, we conducted a hospital-based case-control study at the University of Texas M. D. Anderson Cancer Center during June 2002 to May 2006. Atotal of 626 cases and 530 noncancer controls were frequency matched for race, sex and age (±5 years). Dietary exposure information was collected via personal interview using a meat preparation questionnaire. A significantly greater portion of the cases tha...

  1. Mutagenicity of some alkyl nitrites used as recreational drugs

    Energy Technology Data Exchange (ETDEWEB)

    Dunkel, V.C.; Cameron, T.P. (National Institute of Health, Bethesda (USA)); Rogers-Back, A.M.; Lawlor, T.E.; Harbell, J.W. (Microbiological Associates Inc., Rockville, MD (USA))

    1989-01-01

    When the AIDS epidemic was in its earliest stages, and prior to identification of HIV as the etiological factor, the use of volatile nitrites by the male homosexual community to enhance sexual activities appeared to have a significant role in this disease. Preliminary observations indicated that that portion of the male homosexual community which developed Kaposi's sarcoma were also heavy nitrite users. These nitrites had been demonstrated to be mutagenic in bacteria and thus it was postulated that they could be responsible for the appearance of the sarcoma. To evaluate further the genotoxic activity of these chemicals, six nitrites, including those most commonly used by homosexuals for sexual gratification, were selected for testing in the mouse lymphoma TK {plus minus} and Salmonell typhimurium mutagenicity assays. One chemical, n-amyl nitrite, was negative in the mouse lymphoma assay, while the other five chemicals, n-butyl, isobutyl, iso-amyl, sec-butyl, and n-propyl nitrite, were positive. All six compounds were positive in the Salmonella assay. The mutagenic and known toxic effects of these chemicals remain a concern because a large population of teenagers and young adults continue to abuse these substances.

  2. Preconception exposures to potential germ-cell mutagens

    International Nuclear Information System (INIS)

    Draper, G.

    2008-01-01

    Radiation and other agents can cause germ-cell mutations in animal systems. No human germ-cell mutagen has been identified, but this does not mean that human germ-cells are not vulnerable to mutagenesis. There has been particular concern about the possible health effects on offspring following parental preconception exposure to ionizing radiation - both occupational and therapeutic. A strong association with preconception radiation exposure in the fathers of the cases was found in a case-control study of young people with leukaemia living near the Sellafield nuclear plant in the UK. Subsequent studies of workers occupationally exposed to ionizing radiation have failed to confirm these findings. No statistically significant effects have been reported from studies of possible indicators of germ-cell mutagenesis in the A-bomb survivors. Studies of offspring of cancer survivors who receive radiotherapy and mutagenic chemotherapy have found no evidence of germ-cell mutagenesis. Failure to detect human germ-cell mutagenic agents may be a consequence of inadequate study sizes or insufficiently sensitive laboratory techniques. (authors)

  3. Protection against UV-induced toxicity and lack of mutagenicity of Antarctic Sanionia uncinata

    International Nuclear Information System (INIS)

    Fernandes, A.S; Mazzei, J.L; Oliveira, C.G; Evangelista, H.; Marques, M.R.C.; Ferraz, E.R.A.; Felzenszwalb, I.

    2017-01-01

    Antarctica moss Sanionia uncinata (Hedw.) Loeske is exposed in situ to damaging levels of ultraviolet (UV) radiation. This moss has the ability to respond to UV radiation exposure producing secondary metabolites such as flavonoids, and has been recommended as a potential source of photoprotective compounds and antioxidants. The aim of the present paper was to investigate the free-radical scavenging activity and mutagenic and photomutagenic properties of methanolic (ME), hydroethanolic (HE) and ethanolic (EE) extracts of S. uncinata. The phenolic contents were evaluated by high-performance liquid chromatography (HPLC) and spectrophotometry. The findings showed that ME and EE presented the highest phenolic contents and inhibited free radical-scavenging activity against 2,2′-diphenyl-1 picrylhydrazyl (DPPH) and the HPLC analysis indicated several classes of phenolic acids and flavonoids. The sun protection factors (SPF) were determined by an in vitro method and the results showed significant values. The SPF values of BZ-3 at 50 μg/mL increased significantly in association with ME, HE and EE. The extracts did not induce mutagenicity in auxotrophic Salmonella typhimurium histidine and photomutagenicity was not detected in the TA102 and TA104 strains after exposure to UV-A at doses of up to 6.5 J/cm 2 for the TA102 strain and up to 0.24 J/cm 2 for the TA104 strain. In addition, with the exception of ME, all the extracts induced photoprotective effects in the presence of the TA104 strain at 0.04 J/cm 2 . The present results suggest that S. uncinata extracts did not induce photomutation and showed promise for photoprotection against the photobiological and ROS-inducing effects of the UV-A radiation.

  4. Genotoxicity, mutagenicity and cytotoxicity of carotenoids extracted from ionic liquid in multiples organs of Wistar rats.

    Science.gov (United States)

    Larangeira, Paula Martins; de Rosso, Veridiana Vera; da Silva, Victor Hugo Pereira; de Moura, Carolina Foot Gomes; Ribeiro, Daniel Araki

    2016-11-01

    The ionic liquid or melted salt 1-Butyl-3-methylimidazolium is an alternative process to extract natural pigments, such as carotenoids. Lycopene represents 80-90% of total of carotenoids presents in tomatoes and it has been widely studied due its potent antioxidant action. The aim of this study was to evaluate genotoxicity, mutagenicity and cytotoxicity of carotenoids extracted from ionic liquid using experimental model in vivo. For this purpose, a total of 20 male Wistar rats were distributed into four groups (n=5), as follows: control group; received a corresponding amount of corn oil for 7days by intragastric gavage (i.g.), ionic liquid group, received 10mgkg -1 body weight for 7days by gavage; 10mg carotenoids group, received 10mgkg -1 bw dissolved in corn oil for 7days by gavage and 500mg carotenoids group, received 500mgkg -1 bw dissolved in corn oil for 7days by gavage. Rat liver treated with ionic liquid exhibited moderate histopathological changes randomly distributed in the parenchyma, such as cytoplasmic eosinophilia, apoptotic bodies, inflammatory infiltrate and focal necrosis. DNA damage was found in peripheral blood and liver cells of rats treated with ionic liquid or carotenoids at 500mg. An increase of micronucleated cells and 8-OhDG immunopositive cells were also detected in rats treated with carotenoids at 500mg. In summary, our results demonstrate that recommended dose for human daily intake of carotenoids extracted by ionic liquid did not induce genotoxicity, mutagenicity and cytotoxicity in multiple organs of rats. Copyright © 2016 Elsevier GmbH. All rights reserved.

  5. Mutagenic effects of carbon ions near the range end in plants

    Energy Technology Data Exchange (ETDEWEB)

    Hase, Yoshihiro, E-mail: hase.yoshihiro@jaea.go.jp [Ion Beam Mutagenesis Research Group, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan); Yoshihara, Ryouhei; Nozawa, Shigeki; Narumi, Issay [Ion Beam Mutagenesis Research Group, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan)

    2012-03-01

    To gain insight into the mutagenic effects of accelerated heavy ions in plants, the mutagenic effects of carbon ions near the range end (mean linear energy transfer (LET): 425 keV/{mu}m) were compared with the effects of carbon ions penetrating the seeds (mean LET: 113 keV/{mu}m). Mutational analysis by plasmid rescue of Escherichia coli rpsL from irradiated Arabidopsis plants showed a 2.7-fold increase in mutant frequency for 113 keV/{mu}m carbon ions, whereas no enhancement of mutant frequency was observed for carbon ions near the range end. This suggested that carbon ions near the range end induced mutations that were not recovered by plasmid rescue. An Arabidopsis DNA ligase IV mutant, deficient in non-homologous end-joining repair, showed hyper-sensitivity to both types of carbon-ion irradiation. The difference in radiation sensitivity between the wild type and the repair-deficient mutant was greatly diminished for carbon ions near the range end, suggesting that these ions induce irreparable DNA damage. Mutational analysis of the Arabidopsis GL1 locus showed that while the frequency of generation of glabrous mutant sectors was not different between the two types of carbon-ion irradiation, large deletions (>{approx}30 kb) were six times more frequently induced by carbon ions near the range end. When 352 keV/{mu}m neon ions were used, these showed a 6.4 times increase in the frequency of induced large deletions compared with the 113 keV/{mu}m carbon ions. We suggest that the proportion of large deletions increases with LET in plants, as has been reported for mammalian cells. The nature of mutations induced in plants by carbon ions near the range end is discussed in relation to mutation detection by plasmid rescue and transmissibility to progeny.

  6. Anti mutagenesis of chemical modulators against damage induced by reactor thermal neutrons; Antimutagenesis de moduladores quimicos contra el dano inducido por neutrones termicos de reactor

    Energy Technology Data Exchange (ETDEWEB)

    Zambrano A, F.; Guzman R, J.; Garcia B, A.; Paredes G, L.; Delfin L, A. [Instituto Nacional de Investigaciones Nucleares, Departamentos de Materiales Radiactivos, de Biologia, del Reactor y Gerencia de Aplicaciones Nucleares en la Salud, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    1999-07-01

    The mutations are changes in the genetic information whether for spontaneous form or induced by the exposure of the genetic material to certain agents, called mutagens: chemical or physical (diverse types of radiations). As well as exist a great variety of mutagens and pro mutagens (these last are agents which transform themselves in mutagens after the metabolic activation). Also several chemical compounds exist which are called antimutagens because they reduce the mutagens effect. The C vitamin or ascorbic acid (A A) presents antimutagenic and anti carcinogenic properties. On the other hand a sodium/copper salt derived from chlorophyll belonging to the porphyrin group (C L) contains a chelated metal ion in the center of molecule. It is also an antioxidant, antimutagenic and anti carcinogenic compound, it is called chlorophyllin. The objective of this work is to establish if the A A or the C L will reduce the damages induced by thermal and fast reactor neutrons. (Author)

  7. Radiation-induced mutagenicity and lethality in tryptophan-requiring auxotrophs of escherichia coli

    International Nuclear Information System (INIS)

    Xu Rong; Qian Hongwei; Yao Fenying; Gu Shuzhu; Xu Jiaxin; Bi Hekan; Liu Yuying

    1989-01-01

    Mutation and killing caused by X-ray radiation and 60 Co γ-ray radiation were studied in three different tryptophan-requiring auxotrophs (WP2, Wp2A, Cm 891) of Escherichia coli. These testers are sensitive to base pair substitution mutagens. Cm891 carries a R-factor and is more sensitive than WP2 and WP2A to radiation-induced mutation and lethality. The results of the study show that (1) ionizing radiation was mutagenic to E. coli, (2) the order of mutagenic sensitivity among three strains to ionizing radiation was Cm891 > WP2A > WP2, (3) the dose rate of γ-ray influences mutagenicity and lethalty of E. coli strain, (4) the toxicity and mutagenicity of γ-ray were similar to X-ray when Cm891 was tested, however, γ-ray was more toxic and mutagenic than X-ray to WP2A ang WP2

  8. Role of ozone and granular activated carbon in the removal of mutagenic compounds.

    Science.gov (United States)

    Bourbigot, M M; Hascoet, M C; Levi, Y; Erb, F; Pommery, N

    1986-01-01

    The identification of certain organic compounds in drinking water has led water treatment specialists to be increasingly concerned about the eventual risks of such pollutants to the health of consumers. Our experiments focused on the role of ozone and granular activated carbon in removing mutagenic compounds and precursors that become toxic after chlorination. We found that if a sufficient dose of ozone is applied, its use does not lead to the creation of mutagenic compounds in drinking water and can even eliminate the initial mutagenicity of the water. The formation of new mutagenic compounds seems to be induced by ozonation that is too weak, although these mutagens can be removed by GAC filtration. Ozone used with activated carbon can be one of the best means for eliminating the compounds contributing to the mutagenicity of water. A combined treatment of ozone and activated carbon also decreases the chlorine consumption of the treated water and consequently reduces the formation of chlorinated organic compounds. PMID:3816720

  9. Mutagenicity of urine from nurses handling cytostatic drugs, influence of smoking

    Energy Technology Data Exchange (ETDEWEB)

    Bos, R P; Leenaars, A O; Theuws, J L; Henderson, P T

    1982-01-01

    Mutagenicity towards Salmonella typhimurium TA 100 of urine from smoking nurses, who were occupationally involved in the treatment of patients with cytostatic drugs, was significantly increased in comparison with that of smoking control subjects. Mutagenicity towards Salmonella typhimurium TA 100 was not increased in exposed non-smokers when compared to control non-smokers. In smoking subjects urinary mutagenicity appeared increased towards Salmonella typhimurium TA 1538 in the presence of S-9 mix. Rats pretreated with Aroclor 1254 showed higher mutagenicity in their urine than untreated rats after cyclophosphamide administration. Therefore, the synergistic effect of smoking might be due in part to induction of enzymes involved in the mutagenic activation of cytostatic drugs. Further, the animal experiments showed that cyclophosphamide (the most frequently used mutagenic cytostatic drug) can be absorbed after oral or percutaneous administration. Therefore, it is not excluded that differences in working hygiene between smokers and non-smokers also play a role.

  10. Combined effects of a chemical mutagen and radiation sterilized diet in mutagenicity and reproduction studies in the same mouse

    International Nuclear Information System (INIS)

    Renner, H.W.

    1975-01-01

    The possible intensification of the mutagenic effect of cyclophosphamide (Endoxan) by the feeding of a radiation-sterilized diet (dose, 4.5 Mrad) was studied in 2000 NMRI/Han mice. In a dominant lethal test, males were pretreated with 100 mg Endoxan/kg body weight. The greatest sensitivity towards Endoxan was observed during the late-spermatid stage. No significant differences were detected between the control group (Endoxan plus non-irradiated diet) and the experimental group (Endoxan plus radiation-sterilized diet). In this test, radiation-sterilized feed showed no co-mutagenic effect when combined with Endoxan treatment. In a reproduction study of 7 months duration (continuous mating without lactation periods), the females were treated every 2 wk with 20 mg Endoxan/kg body weight. The decline in litter size with increasing number of litters (i.e. with advancing age of the females) was more pronounced after treatment with the chemical mutagen than in the untreated group. Increases in the frequency of abortions and in premature sterility resulted from Endoxan treatment. During the entire observation period, no effects from the intake of radiation-sterilized food were detected. (author)

  11. Phenomenology of an inducible mutagenic DNA repair pathway in Escherichia coli: SOS repair hypothesis

    International Nuclear Information System (INIS)

    Radman, M.

    1974-01-01

    A hypothesis is proposed according to which E. coli possesses an inducible DNA repair system. This hypothetical repair, which we call SOS repair, is manifested only following damage to DNA, and requires de novo protein synthesis. SOS repair in E. coli requires some known genetic elements: recA + , lex + and probably zab + . Mutagenesis by ultraviolet light is observed only under conditions of functional SOS repair: we therefore suspect that this is a mutation-prone repair. A number of phenomena and experiments is reviewed which at this point can best be interpreted in terms of an inducible mutagenic DNA repair system. Two recently discovered phenomena support the proposed hypothesis: existence of a mutant (tif) which, after a shift to elevated temperature, mimicks the effect of uv irradiation in regard to repair of phage lambda and uv mutagenesis, apparent activation of SOS repair by introduction into the recipient cell of damaged plasmid or Hfr DNA. Several specific predictions based on SOS repair hypothesis are presented in order to stimulate further experimental tests. (U.S.)

  12. Mutagens from the cooking of food. III. Survey by Ames/Salmonella test of mutagen formation in secondary sources of cooked dietary protein

    Energy Technology Data Exchange (ETDEWEB)

    Bjeldanes, L F [Univ. of California, Berkeley; Morris, M M; Felton, J S; Healy, S; Stuermer, D; Berry, P; Timourian, H; Hatch, F T

    1982-01-01

    A survey of mutagen formation during the cooking of a variety of protein-rich foods that are minor sources of protein intake in the American diet is reported (see Bjeldanes, Morris, Felton et al. (1982) for survey of major protein foods). Milk, cheese, tofu and organ meats showed negligible mutagen formation except following high-temperature cooking for long periods of time. Even under the most extreme conditions, tofu, cheese and milk exhibited fewer than 500 Ames/Salmonella typhimurium revertants/100 g equivalents (wet weight of uncooked food), and organ meats only double that amount. Beans showed low mutagen formation after boiling followed by frying (with and without oil). Only boiling of beans followed by baking for 1 hr gave appreciable mutagenicity (3650 revertants/100 g equivalents). Seafood samples gave a variety of results: red snapper, salmon, trout, halibut and rock cod all gave more than 1000 revertants/100 g wet weight equivalents when pan-fried or griddle-fried for about 6 min/side. Baked or poached rock cod and deep-fried shrimp showed no significant mutagen formation. Broiled lamb chops showed mutagen formation similar to that in red meats tested in the preceding paper: 16,000 revertants/100 g equivalents. These findings show that as measured by bioassay in S. typhimurium, most of the food that are minor sources of protein in the American diet are also minor sources of cooking-induced mutagens.

  13. Mutagens from the cooking of food. III. Survey by Ames/Salmonella test of mutagen formation in secondary sources of cooked dietary protein.

    Science.gov (United States)

    Bjeldanes, L F; Morris, M M; Felton, J S; Healy, S; Stuermer, D; Berry, P; Timourian, H; Hatch, F T

    1982-08-01

    A survey of mutagen formation during the cooking of a variety of protein-rich foods that are minor sources of protein intake in the American diet is reported (see Bjeldanes, Morris, Felton et al. (1982) for survey of major protein foods). Milk, cheese, tofu and organ meats showed negligible mutagen formation except following high-temperature cooking for long periods of time. Even under the most extreme conditions, tofu, cheese and milk exhibited fewer than 500 Ames/Salmonella typhimurium revertants/100 g equivalents (wet weight of uncooked food), and organ meats only double that amount. Beans showed low mutagen formation after boiling and boiling followed by frying (with and without oil). Only boiling of beans followed by baking for 1 hr gave appreciable mutagenicity (3650 revertants/100g equivalents). Seafood samples gave a variety of results: red snapper, salmon, trout, halibut and rock cod all gave more than 1000 revertants/100 g wet weight equivalents when pan-fried or griddle-fried for about 6 min/side. Baked or poached rock and deep-fried shrimp showed no significant mutagen formation. Broiled lamb chops showed mutagen formation similar to that in red meats tested in the preceding paper: 16,000 revertants/100 g equivalents. These findings show that as measured by bioassay in S. typhimurium, most of the foods that are minor sources of protein in the American diet are also minor sources of cooking-induced mutagens.

  14. Inhibition of fried meat-induced colorectal DNA damage and altered systemic genotoxicity in humans by crucifera, chlorophyllin, and yogurt.

    Directory of Open Access Journals (Sweden)

    Daniel T Shaughnessy

    2011-04-01

    Full Text Available Dietary exposures implicated as reducing or causing risk for colorectal cancer may reduce or cause DNA damage in colon tissue; however, no one has assessed this hypothesis directly in humans. Thus, we enrolled 16 healthy volunteers in a 4-week controlled feeding study where 8 subjects were randomly assigned to dietary regimens containing meat cooked at either low (100°C or high temperature (250°C, each for 2 weeks in a crossover design. The other 8 subjects were randomly assigned to dietary regimens containing the high-temperature meat diet alone or in combination with 3 putative mutagen inhibitors: cruciferous vegetables, yogurt, and chlorophyllin tablets, also in a crossover design. Subjects were nonsmokers, at least 18 years old, and not currently taking prescription drugs or antibiotics. We used the Salmonella assay to analyze the meat, urine, and feces for mutagenicity, and the comet assay to analyze rectal biopsies and peripheral blood lymphocytes for DNA damage. Low-temperature meat had undetectable levels of heterocyclic amines (HCAs and was not mutagenic, whereas high-temperature meat had high HCA levels and was highly mutagenic. The high-temperature meat diet increased the mutagenicity of hydrolyzed urine and feces compared to the low-temperature meat diet. The mutagenicity of hydrolyzed urine was increased nearly twofold by the inhibitor diet, indicating that the inhibitors enhanced conjugation. Inhibitors decreased significantly the mutagenicity of un-hydrolyzed and hydrolyzed feces. The diets did not alter the levels of DNA damage in non-target white blood cells, but the inhibitor diet decreased nearly twofold the DNA damage in target colorectal cells. To our knowledge, this is the first demonstration that dietary factors can reduce DNA damage in the target tissue of fried-meat associated carcinogenesis.ClinicalTrials.gov NCT00340743.

  15. Genome-wide map of Apn1 binding sites under oxidative stress in Saccharomyces cerevisiae.

    Science.gov (United States)

    Morris, Lydia P; Conley, Andrew B; Degtyareva, Natalya; Jordan, I King; Doetsch, Paul W

    2017-11-01

    The DNA is cells is continuously exposed to reactive oxygen species resulting in toxic and mutagenic DNA damage. Although the repair of oxidative DNA damage occurs primarily through the base excision repair (BER) pathway, the nucleotide excision repair (NER) pathway processes some of the same lesions. In addition, damage tolerance mechanisms, such as recombination and translesion synthesis, enable cells to tolerate oxidative DNA damage, especially when BER and NER capacities are exceeded. Thus, disruption of BER alone or disruption of BER and NER in Saccharomyces cerevisiae leads to increased mutations as well as large-scale genomic rearrangements. Previous studies demonstrated that a particular region of chromosome II is susceptible to chronic oxidative stress-induced chromosomal rearrangements, suggesting the existence of DNA damage and/or DNA repair hotspots. Here we investigated the relationship between oxidative damage and genomic instability utilizing chromatin immunoprecipitation combined with DNA microarray technology to profile DNA repair sites along yeast chromosomes under different oxidative stress conditions. We targeted the major yeast AP endonuclease Apn1 as a representative BER protein. Our results indicate that Apn1 target sequences are enriched for cytosine and guanine nucleotides. We predict that BER protects these sites in the genome because guanines and cytosines are thought to be especially susceptible to oxidative attack, thereby preventing large-scale genome destabilization from chronic accumulation of DNA damage. Information from our studies should provide insight into how regional deployment of oxidative DNA damage management systems along chromosomes protects against large-scale rearrangements. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  16. Mutagens from the cooking of food. II. Survey by Ames/Salmonella test of mutagen formation in the major protein-rich foods of the American diet

    Energy Technology Data Exchange (ETDEWEB)

    Bjeldanes, L.F. (Univ. of California, Berkeley); Morris, M.M.; Felton, J.S.; Healy, S.; Stuermer, D.; Berry, P.; Timourian, H.; Hatch, F.T.

    1982-01-01

    The formation of mutagens in the major cooked protein-rich foods in the US diet was studied in the Ames Salmonella typhimurium test. The nine protein-rich foods most commonly eaten in the USA--ground beef, beef steak, eggs, pork chops, fried chicken, pot-roasted beef, ham, roast beef and bacon--were examined for their mutagenicity towards S. typhimurium TA1538 after normal 'household' cooking (deep frying, griddle/pan frying, baking/roasting, broiling, stewing, braising or boiling at 100-475/sup 0/C). Well-done fried ground beef, beef steak, ham, pork chops and bacon showed significant mutagen formation. For chicken and beef steak high-temperature broiling produced the most mutagenicity, followed by baking/roasting and frying. Stewing, braising and deep frying produced little mutagen. Eggs andd egg products produced mutagens only after cooking at high temperatures (the yolk to a greater extent than the white). Commercially cooked hamburgers showed a wide range of mutagenic activity. We conclude that mutagen formation following cooking of protein-containing foods is a complex function of food type, cooking time and cooking temperature. It seems clear that all the major protein-rich foods if cooked to a well-done state on the griddle (eggs only at temperature above 225/sup 0/C) or by broiling will contain mutagens detectable by the Ames/Salmonella assay. This survey is a step towards determining whether any human health hazard results from cooking protein-rich foods. Further testing in both short- and long-term genotoxicity bioassays and carcinogenesis assays are needed before any human risk extrapolations can be made.

  17. Mutagens from the cooking of food. II. Survey by Ames/Salmonella test of mutagen formation in the major protein-rich foods of the American diet.

    Science.gov (United States)

    Bjeldanes, L F; Morris, M M; Felton, J S; Healy, S; Stuermer, D; Berry, P; Timourian, H; Hatch, F T

    1982-08-01

    The formation of mutagens in the major cooked protein-rich foods in the US diet was studied in the Ames Salmonella typhimurium test. The nine protein-rich foods most commonly eaten in the USA--ground beef, beef steak, eggs, pork chops, fried chicken, pot-roasted beef, ham, roast beef and bacon--were examined for their mutagenicity towards S. typhimurium TA1538 after normal 'household' cooking (deep frying, griddle/pan frying, baking/roasting, broiling, stewing, braising or boiling of 100-475 degrees C). Well-done fried ground beef, beef steak, ham pork chops and bacon showed significant mutagen formation. For chicken and beef steak high-temperature broiling produced the most mutagenicity, followed by baking/roasting and frying. Stewing, braising and deep frying produced little mutagen. Eggs and egg products produced mutagens only after cooking at high temperatures (the yolk to a greater extent than the white). Commercially cooked hamburgers showed a wide range of mutagenic activity. We conclude that mutagen formation following cooking of protein-containing foods is a complex function of food type, cooking time and cooking temperature. It seems clear that all the major protein-rich foods if cooked to a well-done state on the griddle (eggs only at temperatures above 225 degrees C) or by broiling will contain mutagens detectable by the Ames/Salmonella assay. This survey is a step towards determining whether any human health hazard results from cooking protein-rich foods. Further testing in both short- and long-term genotoxicity bioassays and carcinogenesis assays are needed before any human risk extrapolations can be made.

  18. Lethal and mutagenic properties of MMS-generated DNA lesions in Escherichia coli cells deficient in BER and AlkB-directed DNA repair.

    Science.gov (United States)

    Sikora, Anna; Mielecki, Damian; Chojnacka, Aleksandra; Nieminuszczy, Jadwiga; Wrzesinski, Michal; Grzesiuk, Elzbieta

    2010-03-01

    Methylmethane sulphonate (MMS), an S(N)2-type alkylating agent, generates DNA methylated bases exhibiting cytotoxic and mutagenic properties. Such damaged bases can be removed by a system of base excision repair (BER) and by oxidative DNA demethylation catalysed by AlkB protein. Here, we have shown that the lack of the BER system and functional AlkB dioxygenase results in (i) increased sensitivity to MMS, (ii) elevated level of spontaneous and MMS-induced mutations (measured by argE3 --> Arg(+) reversion) and (iii) induction of the SOS response shown by visualization of filamentous growth of bacteria. In the xth nth nfo strain additionally mutated in alkB gene, all these effects were extreme and led to 'error catastrophe', resulting from the presence of unrepaired apurinic/apyrimidinic (AP) sites and 1-methyladenine (1meA)/3-methylcytosine (3meC) lesions caused by deficiency in, respectively, BER and AlkB dioxygenase. The decreased level of MMS-induced Arg(+) revertants in the strains deficient in polymerase V (PolV) (bearing the deletion of the umuDC operon), and the increased frequency of these revertants in bacteria overproducing PolV (harbouring the pRW134 plasmid) indicate the involvement of PolV in the error-prone repair of 1meA/3meC and AP sites. Comparison of the sensitivity to MMS and the induction of Arg(+) revertants in the double nfo alkB and xth alkB, and the quadruple xth nth nfo alkB mutants showed that the more AP sites there are in DNA, the stronger the effect of the lack of AlkB protein. Since the sum of MMS-induced Arg(+) revertants in xth, nfo and nth xth nfo and alkB mutants is smaller than the frequency of these revertants in the BER(-) alkB(-) strain, we consider two possibilities: (i) the presence of AP sites in DNA results in relaxation of its structure that facilitates methylation and (ii) additional AP sites are formed in the BER(-) alkB(-) mutants.

  19. Cytotoxicity, genotoxicity, and mutagenicity of 1-chloro-2-hydroxy-3-butene and 1-chloro-3-buten-2-one, two alternative metabolites of 1,3-butadiene

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xin-Jie; Zeng, Fang-Mao; An, Jing; Yu, Ying-Xin [Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444 (China); Zhang, Xin-Yu, E-mail: xyzhang999@shu.edu.cn [Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444 (China); Elfarra, Adnan A., E-mail: elfarra@svm.vetmed.wisc.edu [Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53706 (United States); Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, WI 53706 (United States)

    2013-08-15

    The cytotoxicity, genotoxicity, and mutagenicity of 1-chloro-2-hydroxy-3-butene (CHB), a known in vitro metabolite of the human carcinogen 1,3-butadiene, have not previously been investigated. Because CHB can be bioactivated by alcohol dehydrogenases to yield 1-chloro-3-buten-2-one (CBO), a bifunctional alkylating agent that caused globin-chain cross-links in erythrocytes, in the present study we investigated the cytotoxic and genotoxic potential of CHB and CBO in human normal hepatocyte L02 cells using the MTT assay, the relative cloning efficiency assay and the comet assay. We also investigated the mutagenic potential of these compounds with the Ames test using Salmonella strains TA1535 and TA1537. The results provide clear evidence for CHB and CBO being both cytotoxic and genotoxic with CBO being approximately 100-fold more potent than CHB. Interestingly, CHB generated both single-strand breaks and alkali-labile sites on DNA, whereas CBO produced only alkali-labile sites. CHB did not directly result in DNA breaks, whereas CBO was capable of directly generating breaks on DNA. Interestingly, both compounds did not induce DNA cross-links as examined by the comet assay. The Ames test results showed that CHB induced point mutation but not frameshift mutation, whereas the toxic effects of CBO made it difficult to reliably assess the mutagenic potential of CBO in the two strains. Collectively, the results suggest that CHB and CBO may play a role in the mutagenicity and carcinogenicity of 1,3-butadiene. - Highlights: • 1-Chloro-2-hydroxy-3-butene (CHB) is cytotoxic and genotoxic in human liver cells. • The CHB metabolite, 1-chloro-3-buten-2-one (CBO) is ∼ 100-fold more toxic than CHB. • CHB and CBO cause DNA alkali-labile sites, but only CBO directly causes DNA breaks. • CHB is mutagenic in the Ames test, but CBO is too toxic in the assay. • The results suggest a role for CHB in 1,3-butadiene genotoxicity and mutagenicity.

  20. Mutagenic potential assessment associated with human exposure to natural radioactivity.

    Science.gov (United States)

    Marcon, Alexandre Endres; Navoni, Julio Alejandro; de Oliveira Galvão, Marcos Felipe; Garcia, Anuska Conde Fagundes Soares; do Amaral, Viviane Souza; Petta, Reinaldo Antônio; Campos, Thomas Ferreira da Costa; Panosso, Renata; Quinelato, Antônio Luiz; de Medeiros, Sílvia Regina Batistuzzo

    2017-01-01

    Lucrécia city, known to harbor a high cancer rate, is located in a semiarid region characterized by the presence of mineral reservoirs, facing a high exposure to metal and natural radioactivity. The present study aimed to assess the environmental scenario at a semiarid region located in Northeastern Brazil. Metal concentration, alpha and beta radiation, and cyanobacteria content in tap water along with indoor radon and gamma emitters (U, K and Th) concentrations were measured. In addition, mutagenic and nuclear instability effects were assessed using buccal micronucleus cytome assay. The study included five samplings corresponding to a period between 2007 and 2009. Drinking water from Lucrécia city presented levels of Mn, Ni and Cr along with cyanobacteria in concentrations one to four times higher than regulatory guidelines considered. Furthermore, high levels of all the tested radionuclides were found. A high percentage of the houses included in this study presented indoor radon concentrations over 100 Bq m -3 . The mean annual effective dose from Lucrécia houses was six times higher than observed in a control region. The levels of exposure in most of the Lucrécia houses were classified as middle to high. A significant mutagenic effect, represented as an increase of micronuclei (MN) frequency and nuclear abnormalities as nuclear buds (NB), binucleated cells (BN), and pyknotic cells (PYC) were found. The results obtained highlight the role of high background radioactivity on the observed mutagenic effect and could help to explain the exacerbated cancer rate reported in this locality. Copyright © 2016. Published by Elsevier Ltd.

  1. Radiation genetic studies in garden pea. Part 2. Caffeine potentiation and chromosome damage

    International Nuclear Information System (INIS)

    Kaul, M.L.H.

    1979-01-01

    The effect of 1.5x10 -2 M caffeine post-treatments over the chromosome damage induced by 4kR X-ray 1.5x10 -2 M Maleic hydrazide (MH) and N-Nitroso-N-urethane (NMU) treatments in the root top cells of a normal and trigenic leaf mutant of Pisum sativum was studied. While MH and NMU produced S-dependent effects, X-rays induced non-delayed S-independent effects. These effects got potentiated by caffeine treatments. With MH, the potentiation occurred when the cells got exposed to caffeine during S-phase and with X-rays, it occurred when the irradiated cells are treated in G 2 or prophase stage. The caffeine potentiation of chromosome damage produced by MH was similar in the roots exposed to caffeine at 16 and 31degC but with NMU, the potentiation was lower at 31 than at 16degC. If the inhibitory effect of caffeine on gap filling process of the damaged DNA is the molecular mechanism responsible for caffeine potentiation of reproductive death it may be the mechanism responsible for the observed chromosome damage in MH treated cells exposed to caffeine during G 1 and S phase. But the X-irradiated cells are insensitive to caffeine at such phases. In these cells caffeine probably acts as an inhibitor of the photoreactivating enzymes for binding sites or with the substrate in the irradiated cells post-treated during G 2 and prophase. However, temperature independence of caffeine potentiation is not compatible with eithr of the above two views. Compared to the normal genotype, the trigenic mutant exhibited an increased chromosomal damage, but not the potentiation. Probably mutant genes reduce the resistance of a genome against mutagenic action, consequently enhance the suseptibility to chromosome damage. (author)

  2. Evaluation of different treatment processes with respect to mutagenic activity in drinking water

    Energy Technology Data Exchange (ETDEWEB)

    Kool, H J; Hrubec, J; van Kreijl, C F; Piet, G J

    1985-12-01

    Treatment processes which are applied in The Netherlands during the preparation of drinking water have been evaluated with regard to introduction and removal of organic mutagens as well as halogenated organics. It appeared that the most efficient processes in reducing mutagenic activity were activated carbon filtration and artificial dune recharge. In general these processes were also the most efficient in removing halogenated organics. Using low doses of chlorine dioxide (less than 1 mg C1O2/l) for safety disinfection of drinking water, no change or substantial less mutagenic activity than by chlorination (1 mg Cl/l) was found. This counts too for the formation of halogenated organics. Transport chlorination of stored river Meuse water was able to introduce or activate mutagenic nitro organics which have not been found previously. Ozone treatment under field conditions showed mostly a tendency to decrease the activity of organic mutagens. It was also shown that dependent on the water quality and treatment conditions a slight increase of mutagenic activity occurred, but this activity would be reduced by increasing the ozone dose. It seems possible to optimize the ozone treatment conditions regarding the level of ozone dose and the contact time to avoid an increase of mutagenic activity. Furthermore it was shown that when a mutagenic raw water source was used a proper combination of treatment processes is able to produce drinking water in which no mutagenic activity could be detected under the test conditions. Finally it is stated that before far-reaching decisions with respect to use mutagenicity data for a selection of water sources or treatment processes will be made, more information on the relation mutagenic activity from drinking water and effects on human health should become available.

  3. Formation of new heterocyclic amine mutagens by heating creatinine, alanine, threonine and glucose.

    Science.gov (United States)

    Skog, K; Knize, M G; Felton, J S; Jägerstad, M

    1992-08-01

    A mixture of alanine, threonine, creatinine and glucose was heated in diethylene glycol and water (5:1, v/v) for 15 min at 200 degrees C. The mutagens formed were purified by high-performance liquid chromatography using the Ames/Salmonella mutagenic activity to guide the purification. The structures of the purified mutagens were determined using UV absorption, mass and NMR spectrometry. A new mutagenic compound with a mass number of 217 was found and its mass spectrum did not correspond to any known mutagen derived from food. This new compound accounted for 4% of the total mutagenic activity. Other mutagenic compounds were identified as MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline), 4,8-DiMeIQx (2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline), and a new mutagen 4,7,8-TriMeIQx (2-amino-3,4,7,8-tetramethylimidazo[4,5-f]quinoxaline) with a mutagenic activity of 73,000 TA98 revertants per microgram. The percentage of the mutagenic activity attributable to MeIQx, 4,8-DiMeIQx and 4,7,8-TriMeIQx was 10%, 70% and 3%, respectively. The yield of MeIQx, 4,8-DiMeIQx and 4,7,8-TriMeIQx was 10, 36 and 6 nmole/mmole creatinine. The formation of TriMeIQx from natural meat components suggests that this new quinoxaline mutagen may be present in cooked foods.

  4. The photoreactivable component in the mutagenic action of ionizing radiations

    International Nuclear Information System (INIS)

    Myasnik, M.N.; Morozov, I.I.; Derevyanko, R.I.

    1980-01-01

    The influence of visible light on the lethal and the mutagenic effects of gamma-radiation on E. coli WP 2 uvrA + and E. coli WP 2 uvrA cells was studied. It was shown that visible light appears to reduce the yield of gamma-induced prototrophs in E. coli WP 2 uvrA cells while the yield of prototrophs in E. coli WP 2 uvrA + stays unchanged. Visible light did not change the survival of gamma-irradiated cells. (author)

  5. Hyper production of alkaline protease by mutagenized bacillus subtilis

    International Nuclear Information System (INIS)

    Qureshi, A.M.; Tanseem, F.

    2010-01-01

    The purpose of this work was to augment the alkaline protease production from Bacillus subtilis by using chemical mutagen (MMS) and UV mutagenesis. A number of mutants were isolated which produce high levels of extra cellular proteases. Analysis of culture supernatants of these mutants had shown that the total amounts of proteolysis activity were increased from 1 to 2 fold over the wild strain. Clones showing promote response were further characterized by analyzing different parameters; like of Temperature, pH substrate concentration and incubation period, to study the activity of protease enzyme. (author)

  6. Mutagenic and carcinogenic structural alerts and their mechanisms of action.

    Science.gov (United States)

    Plošnik, Alja; Vračko, Marjan; Dolenc, Marija Sollner

    2016-09-01

    Knowing the mutagenic and carcinogenic properties of chemicals is very important for their hazard (and risk) assessment. One of the crucial events that trigger genotoxic and sometimes carcinogenic effects is the forming of adducts between chemical compounds and nucleic acids and histones. This review takes a look at the mechanisms related to specific functional groups (structural alerts or toxicophores) that may trigger genotoxic or epigenetic effects in the cells. We present up-to-date information about defined structural alerts with their mechanisms and the software based on this knowledge (QSAR models and classification schemes).

  7. Monitoring ambient air for mutagenicity using the higher plant Tradescantia

    International Nuclear Information System (INIS)

    Schairer, L.A.; Sautkulis, R.C.; Tempel, N.R.

    1982-01-01

    The major emphasis for short-term bioassays has been placed on bacterial and mammalian cell lines. However, for increased perspective on the state-of-the-art of specific in vitro assays it is important to consider the environmental impact on whole organisms by reviewing the contributions made by in vivo assays. This paper will deal exclusively with somatic mutation in the Tradescantia stamen hair: describing the system briefly, demonstrating its relevance to environmental mutagen assessment and discussing its adaptation for in situ ambient atmosphere monitoring

  8. Mutagenic effects of irradiated glucose in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Varma, M.B.; Rao, K.P.; Nandan, S.D.; Rao, M.S.

    1982-01-01

    The mutagenic effects of irradiated glucose were studied using the sex-linked recessive lethal test in Drosophila melanogaster. Oregon K males of D. melanogaster reared on a medium containing 20 or 40% glucose irradiated with a dose of 0.02, 0.10, 0.20, 2 or 5 Mrad #betta#-rays were scored for the induction of sex-linked recessive lethals. The results showed no significant increase in the frequency of X-lethals in Drosophila at any of the dose levels. (author)

  9. DNA damage, acetylcholinesterase activity and lysosomal stability in native and transplanted mussels (Mytilus edulis) in areas close to coastal chemical dumping sites in Denmark

    DEFF Research Database (Denmark)

    Rank, Jette; Lehtonen, Kari K.; Strand, Jakob

    2007-01-01

    Biomarkers of genotoxicity (DNA damage, measured as tail moment in the Comet assay), neurotoxicity (acetylcholinesterase inhibition, AChE) and general stress (lysosomal membrane stability, LMS) were studied in native and transplanted blue mussels (Mytilus edulis) in coastal areas of western Denmark...... of chemical pollution complex, as seen especially in the variability in results on DNA damage, and also in regard to AChE activity. These investigations further stress the importance of understanding the effects of natural factors (salinity, temperature, water levels, rain and storm events) in correct...

  10. o-Phenylenediamine-induced DNA damage and mutagenicity in tobacco seedlinigs is light-dependent

    Czech Academy of Sciences Publication Activity Database

    Gichner, Tomáš; Stavreva, Diana; Breusegem, F.

    2001-01-01

    Roč. 495, - (2001), s. 117-125 ISSN 0027-5107 R&D Projects: GA ČR GA521/99/0532 Institutional research plan: CEZ:AV0Z5038910 Keywords : Comet assay * Ethyl methanesulphonate * Nicotiana tabacum Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.545, year: 2001

  11. Evaluation of DNA damage and mutagenicity induced by lead in tobacco plants

    Czech Academy of Sciences Publication Activity Database

    Gichner, Tomáš; Žnidar, I.; Száková, J.

    2008-01-01

    Roč. 652, č. 2 (2008), s. 186-190 ISSN 1383-5718 R&D Projects: GA ČR GA521/05/0500 Institutional research plan: CEZ:AV0Z50380511 Source of funding: V - iné verejné zdroje Keywords : Comet assay * Nicotiana tabacum L. var. xanthi * Single-cell gel electrophoresis * Somatic mutations Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.363, year: 2008

  12. Effect of mutagen combined action on Chlamydomonas reinhardtii cells. I. Lethal effect dependence on the sequence of mutagen application and on cultivation conditions

    Energy Technology Data Exchange (ETDEWEB)

    Vlcek, D; Podstavkova, S; Dubovsky, J [Komenskeho Univ., Bratislava (Czechoslovakia). Prirodovedecka Fakulta

    1978-01-01

    The effect was investigated of single and combined actions of alkylnitrosourea derivatives (N-methyl-N-nitrosourea and N-ethyl-N-nitrosourea) and UV-radiation on the survival of cells of Chlamydomonas reinhardtii algae in dependence on the sequence of application of mutagens and on the given conditions of cultivation following mutagen activity. In particular, the single phases were investigated of the total lethal effect, i.e., the death of cells before division and their death after division. The most pronounced changes in dependence on the sequence of application of mutagens and on the given conditions of cultivation were noted in cell death before division. In dependence on the sequence of application of mutagens, the effect of the combined action on the survival of cells changed from an additive (alkylnitrosourea + UV-radiation) to a protective effect (UV-radiation + alkylnitrosourea).

  13. Affinity for, and localization of, PEG-functionalized silica nanoparticles to sites of damage in an ex vivo spinal cord injury model

    Directory of Open Access Journals (Sweden)

    Chen Bojun

    2012-09-01

    Full Text Available Abstract Background Traumatic spinal cord injury (SCI leads to serious neurological and functional deficits through a chain of pathophysiological events. At the molecular level, progressive damage is initially revealed by collapse of plasma membrane organization and integrity produced by breaches. Consequently, the loss of its role as a semi-permeable barrier that generally mediates the regulation and transport of ions and molecules eventually results in cell death. In previous studies, we have demonstrated the functional recovery of compromised plasma membranes can be induced by the application of the hydrophilic polymer polyethylene glycol (PEG after both spinal and brain trauma in adult rats and guinea pigs. Additionally, efforts have been directed towards a nanoparticle-based PEG application. The in vivo and ex vivo applications of PEG-decorated silica nanoparticles following CNS injury were able to effectively and efficiently enhance resealing of damaged cell membranes. Results The possibility for selectivity of tetramethyl rhodamine-dextran (TMR dye-doped, PEG-functionalized silica nanoparticles (TMR-PSiNPs to damaged spinal cord was evaluated using an ex vivo model of guinea pig SCI. Crushed and nearby undamaged spinal cord tissues exhibited an obvious difference in both the imbibement and accumulation of the TMR-PSiNPs, revealing selective labeling of compression-injured tissues. Conclusions These data show that appropriately functionalized nanoparticles can be an efficient means to both 1. carry drugs, and 2. apply membrane repair agents where they are needed in focally damaged nervous tissue.

  14. DNA polymerases κ and ζ cooperatively perform mutagenic translesion synthesis of the C8–2′-deoxyguanosine adduct of the dietary mutagen IQ in human cells

    Science.gov (United States)

    Bose, Arindam; Pande, Paritosh; Jasti, Vijay P.; Millsap, Amy D.; Hawkins, Edward K.; Rizzo, Carmelo J.; Basu, Ashis K.

    2015-01-01

    The roles of translesion synthesis (TLS) DNA polymerases in bypassing the C8–2′-deoxyguanosine adduct (dG-C8-IQ) formed by 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a highly mutagenic and carcinogenic heterocyclic amine found in cooked meats, were investigated. Three plasmid vectors containing the dG-C8-IQ adduct at the G1-, G2- or G3-positions of the NarI site (5′-G1G2CG3CC-3′) were replicated in HEK293T cells. Fifty percent of the progeny from the G3 construct were mutants, largely G→T, compared to 18% and 24% from the G1 and G2 constructs, respectively. Mutation frequency (MF) of dG-C8-IQ was reduced by 38–67% upon siRNA knockdown of pol κ, whereas it was increased by 10–24% in pol η knockdown cells. When pol κ and pol ζ were simultaneously knocked down, MF of the G1 and G3 constructs was reduced from 18% and 50%, respectively, to IQ. We conclude that pol κ and pol ζ cooperatively carry out the majority of the error-prone TLS of dG-C8-IQ, whereas pol η is involved primarily in its error-free bypass. PMID:26220181

  15. Mutagenicity of basic fractions derived from lamb and beef cooked by common household methods.

    Science.gov (United States)

    Barrington, P J; Baker, R S; Truswell, A S; Bonin, A M; Ryan, A J; Paulin, A P

    1990-03-01

    Mutagen production was examined in lamb and beef in relation to certain common household cooking methods. Mutagenicity was assessed, after extraction of the basic fraction of cooked meat samples, using Salmonella typhimurium strain TA1538 with added rat-liver S-9 homogenate. Little or no mutagenicity was found in barbecued lamb chops, in microwave-cooked lamb chops, sirloin steak, leg of lamb, or rolled beef loaf, in roasted leg of lamb or rolled beef loaf, in stewed blade steak or in boiled chuck steak. However, the basic fraction from well-done, edible fried or grilled meat contained mutagenic activity equivalent to approximately 30,000 TA1538 revertants/100 g cooked meat. It was found tht the mutagenic activity of grilled lamb chops, sirloin and rump steaks was directly related to the average surface temperatures attained during cooking. Use of butter as a frying medium was particularly associated with higher mutagenicity in meat samples. Fried meats (rump and fillet steaks) generally yielded higher mutagenic activity than did grilled meats (rump steak, lamb chops) at comparable temperatures of the cooking medium. Using similar cooking procedures, lamb did not differ markedly from beef in mutagenic activity.

  16. Mutagenicity and cytotoxicity of two regioisomeric mercapturic acids and cysteine S-conjugates of trichloroethylene.

    NARCIS (Netherlands)

    Commandeur, J.N.M.; Boogaard, P.J.; Mulder, G.J.; Vermeulen, N.P.E.

    1991-01-01

    The mutagenicity, cytotoxicity and metabolism of two regioisomic l-cysteine- and N-acetyl-l-cysteine-S-conjugates of trichloroethylene were studied. The 1,2-dichlorovinyl(1,2-DCV) isomers of both the cysteine conjugate and the mercapturate were much stronger mutagens in the Ames test with Salmonella

  17. Mutagenicity assessment of aerosols in emissions from wood combustion in Portugal

    International Nuclear Information System (INIS)

    Vu, B.; Alves, C.A.; Gonçalves, C.; Pio, C.; Gonçalves, F.; Pereira, R.

    2012-01-01

    Polycyclic aromatic hydrocarbon (PAH) extracts of fine particles (PM 2.5 ) collected from combustion of seven wood species and briquettes were tested for mutagenic activities using Ames test with Salmonella typhimurium TA98 and TA100. The woods were Pinus pinaster (maritime pine), Eucalyptus globulus (eucalypt), Quercus suber (cork oak), Acacia longifolia (golden wattle), Quercus faginea (Portuguese oak), Olea europea (olive), and Quercus ilex rotundifolia (Holm oak). Burning experiments were done using woodstove and fireplace, hot start and cold start conditions. A mutagenic response was recorded for all species except golden wattle, maritime pine, and briquettes. The mutagenic extracts were not correlated with high emission factors of carcinogenic PAHs. These extracts were obtained both from two burning appliances and start-up conditions. However, fireplace seemed to favour the occurrence of mutagenic emissions. The negative result recorded for golden wattle was interesting, in an ecological point of view, since after confirmation, this invasive species, can be recommended for domestic use. - Highlights: ► Both woodstove and fireplace, either with a cold or hot start, produce emissions with mutagenic potential. ► The high level of carcinogenic PAHs in combustion emissions was not correlated with mutagenicity. ► The golden wattle, an invasive species, produced no mutagenic emissions. - Wood smoke from fireplace burning of dominant forest species displayed strong mutagenic activity without a significant correlation with carcinogenic PAHs emission factors.

  18. Induction of forward gene mutations in saccharomycetes. Comparison of efficiencies of different mutagens

    International Nuclear Information System (INIS)

    Zakharov, I.A.; Gracheva, L.M.; Ivanov, E.L.; Koval'tsova, S.V.; Kozhina, T.N.; Korolev, V.G.; Fedorova, I.V.; Shanshiashvili, T.A.; Yadgarov, Kh.T.

    1981-01-01

    The data on the induction of forward mutations in locus ade 2 of the wild haploid of Saccharomyces cerevisiae yeasts by three types of mutagens-chamical mutagens, various radiations and defferent isotopes incorporated in the cell - are generalyzed. The ratio of mutation frequency observed at different doses of mutagen to the survival rate logarithm for the same doses is expressed as rectilinear regression M=m(-1 nS). The application of the same mutation system in the case of all studied mutagens allows to consider the inclination value ''m'' to be the characteristic of mutagen efficiency. We propose to call the ratio of the efficiency of a given mutagen to the efficiency of γ-rays (msub(x)/msub(γ)) - the relative mutagenous effifiency (RME). According to the decrease of this index the studied mutagens have stood in the following succession: ethylene imine (EI), nitrosomethylurea (NMU) 89 Sr, UV rays, 35 S, 91 Y, 33 P, 32 P, acridine-yprite, β-radiation ( 32 P), γ-rays, hard X-rays, 3 H, soft X-rays, neutrons, 125 I [ru

  19. A comparison of mutagen production in fried ground chicken and beef: effect of supplemental creatine.

    Science.gov (United States)

    Knize, M G; Shen, N H; Felton, J S

    1988-11-01

    Ground chicken breast and ground beef with either endogenous or a 10-fold increase in the concentration of creatine were fried at 220 degrees C for 10 min per side. One patty (100 g) of chicken meat yielded 120,000 Salmonella (TA1538) revertants following metabolic activation. The pan residues had 39% of the total activity. Added creatine (10-fold the endogenous level) increased mutagen yields an average of 2-fold. Beef cooked under identical conditions yielded 150,000 revertants/100 g for the meat patties and pan residues combined. Added creatine to beef prior to cooking increased mutagen yields 3-fold. The mutagenic profiles following initial HPLC separation showed that chicken samples with endogenous or added creatine were remarkably similar. Chicken and beef HPLC mutagenicity profiles were also similar to each other, but not identical. This suggests that the general mutagen-forming reactions with the two different types of muscle are qualitatively similar with only minor quantitative differences. The pan residues from both meat types with and without added creatine showed some significant differences in the mutagen peak profile. This work suggests that the types of mutagens formed in chicken are similar to those formed in beef and that creatine appears to be involved in the formation of all the mutagenic compounds produced from fried muscle tissue.

  20. Use of genetic toxicity data in GHS mutagenicity classification and labeling of substances.

    Science.gov (United States)

    Ball, Nicholas S; Hollnagel, Heli M

    2017-06-01

    One of the key outcomes of testing the potential genotoxicity or mutagenicity of a substance is the conclusion on whether the substance should be classified as a germ cell mutagen and the significance of this for other endpoints such as carcinogenicity. The basis for this conclusion are the criteria presented in classification and labelling systems such as the Globally Harmonized System for classification and labeling (GHS). This article reviews the classification criteria for germ cell mutagenicity and carcinogenicity and how they are applied to substances with evidence of mutagenicity. The implications and suitability of such a classification for hazard communication, risk assessment, and risk management are discussed. It is proposed that genotoxicity assessments should not focus on specifically identifying germ cell mutagens, particularly given the challenges associated with communicating this information in a meaningful way. Rather the focus should be on deriving data to characterize the mode of action and for use in the risk assessment of mutagens, which could then feed into a more robust, risk based management of mutagenic substances versus the current more hazard based approaches. Environ. Mol. Mutagen. 58:354-360, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  1. Effect of eugenol on the genotoxicity of established mutagens in the liver

    NARCIS (Netherlands)

    Rompelberg, C.J.M.; Evertz, S.J.C.J.; Bruijntjes-Rozier, G.C.D.M.; Heuvel, P.D. van den; Verhagen, H.

    1996-01-01

    The influence of in vivo treatment with eugenol on established mutagens was studied to determine whether eugenol has antigenotoxic potential. The effects of eugenol in rats was investigated in the unscheduled DNA synthesis (UDS) assay with established mutagens and the Salmonella typhimurium

  2. Carcinogenic and mutagenic properties of chemicals in drinking water

    Energy Technology Data Exchange (ETDEWEB)

    Bull, R J

    1985-12-01

    Isolated cases of careless handling of industrial and domestic waste has lead to a wide variety of dangerous chemicals being inadvertently introduced into drinking water. However, chemicals with established carcinogenic and mutagenic properties that occur with a high frequency and in multiple locations are limited in number. To date, the chief offenders have been chemicals of relatively low carcinogenic potency. Some of the more common chemicals are formed as by-products of disinfection. The latter process is generally regarded as essential to the production of a ''microbiologically safe'' drinking water. Consequently, any reductions in what may be a relatively small carcinogenic risk must be balanced against a potential for a higher frequency of waterborne infectious disease. The results of recent toxicological investigations will be reviewed to place the potential carcinogenic and mutagenic hazards frequently associated with drinking water into perspective. First, evidence for the carcinogenicity of certain volatile organic compounds such as trichloroethylene, tetrachloroethylene and carbon tetrachloride is considered. Second, the carcinogenic activity that can be ascribed to various by-products of chlorination is reviewed in some detail. Finally, recent evidence that other chemicals derived from the treatment and distribution of drinking water is highlighted as an area requiring move systematic attention. 72 references.

  3. The mutagenic potential of high flash aromatic naphtha.

    Science.gov (United States)

    Schreiner, C A; Edwards, D A; McKee, R H; Swanson, M; Wong, Z A; Schmitt, S; Beatty, P

    1989-06-01

    Catalytic reforming is a refining process that converts naphthenes to aromatics by dehydrogenation to make higher octane gasoline blending components. A portion of this wide boiling range hydrocarbon stream can be separated by distillation and used for other purposes. One such application is a mixture of predominantly 9-carbon aromatic molecules (C9 aromatics, primarily isomers of ethyltoluene and trimethylbenzene), which is removed and used as a solvent--high-flash aromatic naphtha. A program was initiated to assess the toxicological properties of high-flash aromatic naphtha since there may be human exposure through inhalation or external body contact. The current study was conducted partly to assess the potential for mutagenic activity and also to assist in an assessment of carcinogenic potential. The specific tests utilized included the Salmonella/mammalian microsome mutagenicity assay, the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) forward mutation assay in CHO cells, in vitro chromosome aberration and sister chromatid exchange (SCE) assays in CHO cells, and an in vivo chromosome aberration assay in rat bone marrow.

  4. Mutagenicity of diesel exhaust soot dispersed in phospholipid surfactants

    Energy Technology Data Exchange (ETDEWEB)

    Wallace, W.; Keane, M.; Xing, S.; Harrison, J.; Gautam, M.; Ong, T.

    1994-06-01

    Organics extractable from respirable diesel exhaust soot particles by organic solvents have been known for some time to be direct acting frameshift mutagens in the Ames Salmonella typhimurium histidine reversion assay. Upon deposition in a pulmonary alveolus or respiratory bronchiole, respirable diesel soot particles will contact first the hypophase which is coated by and laden with surfactants. To model interactions of soot and pulmonary surfactant, the authors dispersed soots in vitro in the primary phospholipid pulmonary surfactant dipalmitoyl glycerophosphorylcholine (lecithin) (DPL) in physiological saline. They have shown that diesel soots dispersed in lecithin surfactant can express mutagenic activity, in the Ames assay system using S. typhimurium TA98, comparable to that expressed by equal amounts of soot extracted by dichloromethane/dimethylsulfoxide (DCM/DMSO). Here the authors report additional data on the same system using additional exhaust soots and also using two other phospholipids, dipalmitoyl glycerophosphoryl ethanolamine (DPPE), and dipalmitoyl phosphatidic acid (DPPA), with different ionic character hydrophilic moieties. A preliminary study of the surfactant dispersed soot in an eucaryotic cell test system also is reported.

  5. Molecular dosimetry of the chemical mutagen ethyl methanesulfonate

    International Nuclear Information System (INIS)

    Zeeland, A.A. van; Aaron, C.S.; Mohn, G.R.; Hung, C.Y.; Brockman, H.E.

    1983-01-01

    Extending previous work with E. coli and mammalian cells in culture, forward-mutation frequencies induced by ethyl methanesulfonate (EMS) were quantitatively compared in Neurospora crassa and Saccharomyces cerevisiae under standardized conditions. Concomitantly, the actual dose to DNA was measured by determining the amount of radioactivity bound to DNA after treatment with tritium-labeled EMS. After exposure to EMS (2.5-50 mM), alkylation levels in N. crassa and S. cerevisiae were similar to those previously determined in E. coli and cultured mammalian cells. Consistently, there was a slightly less than proportional increase of the DNA alkylation level with the exposure concentration of the mutagen. Forward mutagenesis induced in yeast and N. crassa showed exponential kinetics with exponents of 1.5 and 2.6, respectively. These results are similar to those previously reported with E. coli, which differed from the results with cultured mammalian cells, where a linear dose-effect relationship between exposure and genetic effect was observed. These differences may reflect differences in the fate of EMS-induced adducts by cellular DNA repair systems, but are not due to initial differences in DNA alkylation levels. The fate and persistence of specific DNA adducts potentially responsible for pre-mutagenic changes are under investigation. (orig.)

  6. Detection of mutagens in water-distribution systems after disinfection.

    Science.gov (United States)

    Guzzella, Licia; Di Caterino, Filomena; Monarca, Silvano; Zani, Claudia; Feretti, Donatella; Zerbini, Ilaria; Nardi, Giuseppe; Buschini, Annamaria; Poli, Paola; Rossi, Carlo

    2006-09-19

    This research examined the quality of water-before and after distribution-of four drinking-water production plants located in Northern Italy, two of which collected water from local aquifers and two from the River Po. A battery of genotoxicity assays for monitoring drinking-water was performed to assess the quality of the water produced by the treatment plants under study. Three different sampling stations were selected at each plant, one right at the outlet of the treatment plant and two along with the distribution pipelines. Raw river water was also sampled and analysed as a control. The water samples (500 l) were concentrated on silica C18 cartridges and the extracts were tested in in vitro mutagenicity assays (Salmonella/microsome assay with strains TA 98 and TA 100; SOS Chromotest with Escherichia coli strain PQ37); gene conversion, point mutation and mitochondrial DNA mutability assays with the diploid Saccharomyces cerevisiae strain D7 and a toxicity test using the bioluminescent bacterium Vibrio fischeri (Microtox). The Microtox test and the mitochondrial DNA mutability assay showed the greatest sensitivity towards toxic or mutagenic substances in the water extracts considered. The results show that this battery of short-term tests is applicable in the routine monitoring of drinking-water quality before and after distribution.

  7. The use of organic solvents in mutagenicity testing.

    Science.gov (United States)

    Abbondandolo, A; Bonatti, S; Corsi, C; Corti, G; Fiorio, R; Leporini, C; Mazzaccaro, A; Nieri, R; Barale, R; Loprieno, N

    1980-10-01

    13 organic substances (dimethylsulfoxide, methanol, ethanol, n-propyl alcohol, sec-butyl alcohol, tert-butyl alcohol, dl-sec-amyl alcohol, ethylene glycol, ethylene glycol monomethyl ether, 1,4-diethylene dioxide, acetone, methyl acetate and formamide) were considered from the standpoint of their use as solvents for water-insoluble chemicals to be tested for mutagenicity. First, the effect of these solvents on cell survival was studied in the yeast Schizosaccharomyces pombe and in V79 Chinese hamster cells. 8 solvents showing relatively low toxicity on either cell system (dimethylsulfoxide, ethanol, ethylene glycol, ethylene glycol monomethyl ether, 1,4-diethylene dioxide, acetone, methyl acetate and formamide) were tested for their effect on aminopyrine demethylase. 4 solvents (ethanol, 1,4-diethylene dioxide, methyl acetate and formamide) showed a more or less pronounced adverse effect on the microsomal enzymic activity. The remaining 4 and methanol (whose effect on aminopyrine demethylase was not testable) were assayed for mutagenicity in S. pombe. They all gave negative results both with and without the post-mitochondrial fraction from mouse liver.

  8. UV light-induced cyclobutane pyrimidine dimers are mutagenic in mammalian cells

    International Nuclear Information System (INIS)

    Protic-Sabljic, M.; Tuteja, N.; Munson, P.J.; Hauser, J.; Kraemer, K.H.; Dixon, K.

    1986-01-01

    We used a simian virus 40-based shuttle vector plasmid, pZ189, to determine the role of pyrimidine cyclobutane dimers in UV light-induced mutagenesis in monkey cells. The vector DNA was UV irradiated and then introduced into monkey cells by transfection. After replication, vector DNA was recovered from the cells and tested for mutations in its supF suppressor tRNA marker gene by transformation of Escherichia coli carrying a nonsense mutation in the beta-galactosidase gene. When the irradiated vector was treated with E. coli photolyase prior to transfection, pyrimidine cyclobutane dimers were removed selectively. Removal of approximately 90% of the pyrimidine cyclobutane dimers increased the biological activity of the vector by 75% and reduced its mutation frequency by 80%. Sequence analysis of 72 mutants recovered indicated that there were significantly fewer tandem double-base changes and G X C----A X T transitions (particularly at CC sites) after photoreactivation of the DNA. UV-induced photoproducts remained (although at greatly reduced levels) at all pyr-pyr sites after photoreactivation, but there was a relative increase in photoproducts at CC and TC sites and a relative decrease at TT and CT sites, presumably due to a persistence of (6-4) photoproducts at some CC and TC sites. These observations are consistent with the fact that mutations were found after photoreactivation at many sites at which only cyclobutane dimers would be expected to occur. From these results we conclude that UV-induced pyrimidine cyclobutane dimers are mutagenic in DNA replicated in monkey cells

  9. Effect of physical and chemical mutagens on morphological parameters in garlic

    International Nuclear Information System (INIS)

    Choudhary, A.D.; Dnyansagar, V.R.

    1980-01-01

    Cloves of garlic (Allium sativum Linn.) were treated with various doses of gamma rays and different concentrations of ethylmethane sulphonate, diethyl sulphate and ethyleneimine. The effect of mutagens was studied in respect of morphological parameters such as sprouting, survival, sprout height, plant height, number and size of leaves, number of cloves and weight of bulb. In case of mutagen treatment the percentage of sprouting and survival as well as sprout height were found to be decreased with an increase in the dose/concentration of the mutagen. The effect of mutagen on leaf size and number was inhibitory. However, the number of cloves and weight of bulb were found to be increased at lower dose concentration of mutagens. (author)

  10. Studies on mutagenic effect on genetic variability in green gram (Vigna radiata (L. ) Wilczek)

    Energy Technology Data Exchange (ETDEWEB)

    Krishnaswami, S; Rathinam, M [Tamil Nadu Agricultural Univ. Coimbatore (India). Dept. of Agricultural Botany

    1982-03-01

    With a view to finding out the effect of mutagenic treatments on heritability in green gram, two cultivars, showing extremes of sensitivity to mutagen, were subjected to two levels each of gamma irradiation and EMS separately and conjointly and the M/sub 2/ generation raised. Families of the higher dose in each treatment were advanced to the M/sub 3/ and the genetic parameters of the various growth and yield attributes, besides seed yield, studied. Barring plant height, heritability of all other traits registered an increase under the mutagen effect. No consistency was evident in the superiority of one mutagen over the other, their behaviour varying with the cultivar and the character studied. Consequent to enhancement in heritability, correlations between the characters underwent alterations under the mutagens.

  11. Mutagenic effects of β-rays on rice (oryza sativa L.)

    International Nuclear Information System (INIS)

    Wang Cailian; Chen Qiufang; Shen Mei; Xu Gang

    1994-07-01

    The mutagenic effects of 14 C and some other mutagenic factors were compared, and the relationships between mutagenic effects of 14 C and treated stages, doses and methods were studied with different rice varieties as test materials. The mutation rates of heading date and plant height were observed in M 2 . The results showed that the mutagenic effects of 14 C were better than those of other mutagenic factors tested. It is most effective for inducing early-maturing mutation to treat plants with the doses of 333 x 10 4 Bq/plant at the stage of pollen mother cell formation; but for dwarf mutation , they were treated with 74 x 10 4 Bq/plant at the stage of pistil and stamen formation to pollen mother cell formation. As a best treating method, Na 2 14 CO 3 solution was injected to plant bases

  12. Scanning electron-microscopic and X-ray-microanalytic observation of diesel-emission particles associated with mutagenicity

    International Nuclear Information System (INIS)

    Nakashima, K.; Yoshitsugu, K.; Tokiwa, H.; Fukuoka Environmental Research Center

    1983-01-01

    The particles formed by diesel combustion, which may contain various mutagenic chemicals like polycyclic aromatic hydrocarbons (PAH), are analyzed in their morphology by scanning electron microscopy; their sulfur content is detected by X-ray microanalysis, and mutagenicity is tested with a Salmonella typhimurium bioassay. The authors find a close correlation between sulfur content and mutagenicity of PAH. (Auth.)

  13. Mutagenic and cytotoxic properties of 6-thioguanine, S6-methylthioguanine, and guanine-S6-sulfonic acid.

    Science.gov (United States)

    Yuan, Bifeng; Wang, Yinsheng

    2008-08-29

    Thiopurine drugs, including 6-thioguanine ((S)G), 6-mercaptopurine, and azathioprine, are widely employed anticancer agents and immunosuppressants. The formation of (S)G nucleotides from the thiopurine prodrugs and their subsequent incorporation into nucleic acids are important for the drugs to exert their cytotoxic effects. (S)G in DNA can be methylated by S-adenosyl-l-methionine to give S(6)-methylthioguanine (S(6)mG) and oxidized by UVA light to render guanine-S(6)-sulfonic acid ((SO3H)G). Here, we constructed single-stranded M13 shuttle vectors carrying a (S)G, S(6)mG, or (SO3H)G at a unique site and allowed the vectors to propagate in wild-type and bypass polymerase-deficient Escherichia coli cells. Analysis of the replication products by using the competitive replication and adduct bypass and a slightly modified restriction enzyme digestion and post-labeling assays revealed that, although none of the three thionucleosides considerably blocked DNA replication in all transfected E. coli cells, both S(6)mG and (SO3H)G were highly mutagenic, which resulted in G-->A mutation at frequencies of 94 and 77%, respectively, in wild-type E. coli cells. Deficiency in bypass polymerases does not result in alteration of mutation frequencies of these two lesions. In contrast to what was found from previous steady-state kinetic analysis, our data demonstrated that 6-thioguanine is mutagenic, with G-->A transition occurring at a frequency of approximately 10%. The mutagenic properties of 6-thioguanine and its derivatives revealed in the present study offered important knowledge about the biological implications of these thionucleosides.

  14. High-definition fiber tracking for assessment of neurological deficit in a case of traumatic brain injury: finding, visualizing, and interpreting small sites of damage.

    Science.gov (United States)

    Shin, Samuel S; Verstynen, Timothy; Pathak, Sudhir; Jarbo, Kevin; Hricik, Allison J; Maserati, Megan; Beers, Sue R; Puccio, Ava M; Boada, Fernando E; Okonkwo, David O; Schneider, Walter

    2012-05-01

    For patients with traumatic brain injury (TBI), current clinical imaging methods generally do not provide highly detailed information about the location of axonal injury, severity of injury, or expected recovery. In a case of severe TBI, the authors applied a novel high-definition fiber tracking (HDFT) to directly visualize and quantify the degree of axonal fiber damage and predict functional deficits due to traumatic axonal injury and loss of cortical projections. This 32-year-old man sustained a severe TBI. Computed tomography and MRI revealed an area of hemorrhage in the basal ganglia with mass effect, but no specific information on the location of axonal injury could be obtained from these studies. Examinations of the patient at Week 3 and Week 8 after TBI revealed motor weaknesses of the left extremities. Four months postinjury, 257-direction diffusion spectrum imaging and HDFT analysis was performed to evaluate the degree of axonal damage in the motor pathway and quantify asymmetries in the left and right axonal pathways. High-definition fiber tracking was used to follow corticospinal and corona radiata pathways from the cortical surface to the midbrain and quantify projections from motor areas. Axonal damage was then localized by assessing the number of descending fibers at the level of the cortex, internal capsule, and midbrain. The motor deficit apparent in the clinical examinations correlated with the axonal losses visualized using HDFT. Fiber loss estimates at 4 months postinjury accurately predicted the nature of the motor deficits (severe, focal left-hand weakness) when other standard clinical imaging modalities did not. A repeat scan at 10 months postinjury, when edema and hemorrhage had receded, replicated the fiber loss. Using HDFT, the authors accurately identified the presence and location of damage to the underlying white matter in this patient with TBI. Detailed information of injury provided by this novel technique holds future potential for

  15. Inhibitors of acid secretion can benefit gastric wound repair independent of luminal pH effects on the site of damage

    Science.gov (United States)

    Demitrack, Elise S; Aihara, Eitaro; Kenny, Susan; Varro, Andrea; Montrose, Marshall H

    2012-01-01

    Background and aims The authors’ goal was to measure pH at the gastric surface (pHo) to understand how acid secretion affects the repair of microscopic injury to the gastric epithelium. Methods Microscopic gastric damage was induced by laser light, during confocal/two-photon imaging of pH-sensitive dyes (Cl-NERF, BCECF) that were superfused over the mucosal surface of the exposed gastric corpus of anaesthetised mice. The progression of repair was measured in parallel with pHo. Experimental conditions included varying pH of luminal superfusates, and using omeprazole (60 mg/kg ip) or famotidine (30 mg/kg ip) to inhibit acid secretion. Results Similar rates of epithelial repair and resting pHo values (~pH 4) were reported in the presence of luminal pH 3 or pH 5. Epithelial repair was unreliable at luminal pH 2 and pHo was lower (2.5±0.2, P pH 3). Epithelial repair was slower at luminal pH 7 and pHo was higher (6.4±0.1, PpH 3 or pH 7, omeprazole reduced maximal damage size and accelerated epithelial repair, although only at pH 3 did omeprazole further increase surface pH above the level caused by imposed damage. At luminal pH 7, famotidine also reduced maximal damage size and accelerated epithelial repair. Neither famotidine nor omeprazole raised plasma gastrin levels during the time course of the experiments. Conclusions Epithelial repair in vivo is affected by luminal pH variation, but the beneficial effects of acutely blocking acid secretion extend beyond simply raising luminal and/or surface pH. PMID:21997560

  16. Human telomeres are hypersensitive to UV-induced DNA Damage and refractory to repair.

    Directory of Open Access Journals (Sweden)

    Patrick J Rochette

    2010-04-01

    Full Text Available Telomeric repeats preserve genome integrity by stabilizing chromosomes, a function that appears to be important for both cancer and aging. In view of this critical role in genomic integrity, the telomere's own integrity should be of paramount importance to the cell. Ultraviolet light (UV, the preeminent risk factor in skin cancer development, induces mainly cyclobutane pyrimidine dimers (CPD which are both mutagenic and lethal. The human telomeric repeat unit (5'TTAGGG/CCCTAA3' is nearly optimal for acquiring UV-induced CPD, which form at dipyrimidine sites. We developed a ChIP-based technique, immunoprecipitation of DNA damage (IPoD, to simultaneously study DNA damage and repair in the telomere and in the coding regions of p53, 28S rDNA, and mitochondrial DNA. We find that human telomeres in vivo are 7-fold hypersensitive to UV-induced DNA damage. In double-stranded oligonucleotides, this hypersensitivity is a property of both telomeric and non-telomeric repeats; in a series of telomeric repeat oligonucleotides, a phase change conferring UV-sensitivity occurs above 4 repeats. Furthermore, CPD removal in the telomere is almost absent, matching the rate in mitochondria known to lack nucleotide excision repair. Cells containing persistent high levels of telomeric CPDs nevertheless proliferate, and chronic UV irradiation of cells does not accelerate telomere shortening. Telomeres are therefore unique in at least three respects: their biophysical UV sensitivity, their prevention of excision repair, and their tolerance of unrepaired lesions. Utilizing a lesion-tolerance strategy rather than repair would prevent double-strand breaks at closely-opposed excision repair sites on opposite strands of a damage-hypersensitive repeat.

  17. Studies on mutagenic activity of 60Co γ-ray irradiated rape pollen

    International Nuclear Information System (INIS)

    He Weishun; Liu Aihua; Lin Shiying; Xiong Xikun

    1989-01-01

    In the present study on disinfection, the rape pollen was irradiated with 2.5 kGy 60 Co γ-ray. Micronuclei, sister chromatid exchanges (SCE) of bone marrow cells and chromosomal aberrations of meiotic cells in mice were used as an indicater of chromosomal damage to study the mutagenicity of irradiated rape pollen. The results are as follows: (1) The frequency of micronuclei in polychromatic erythrocytes is 2.00 per mille; nucleated cells is 0.8 per mille in control group. In the numbers of polychromatic erythrocytes and nucleated cells with micronuclei, there is no obviously difference in irradiated and unirradiated groups. (2) SCE incidence of control group is 2.01 ± 0.12/cell. No significant difference in the frequency of SCE exists between non-irradiated rape pollen and the control groups. But the frequency of SCE in irradiated rape pollen group (3000 mg/kg/day x 7) is 2.36 ± 0.12/cell; high dose group (6000 mg/kg/day x 7) is 2.96 ± 0.14/cell. In comparison with control group, there is a significant difference. (3) The chromatid breaks, fragments, and univalents in primary spermatocytes have been obseved. The frequencies of chromosomal aberration showed no obviously difference among irradiated and non-irradiated rape pollen groups

  18. Structural specificity in the lethal and mutagenic activity of furocoumarins in yeast cells

    International Nuclear Information System (INIS)

    Averbeck, D.; Chandra, P.; Biswas, R.K.; Gesellschaft fuer Strahlen- und Umweltforschung m.b.H., Frankfurt am Main

    1975-01-01

    Using monofunctional (Angelicin) and bifunctional furocoumarins (Psoralen and 8 Methoxypsoralen) plus 365 nm light it is shown that both kinds of damage, the induced monoadducts and/or crosslinks in DNA, provoke lethal and mutagenic effects in haploid and diploid cells of Saccharomyces cerevisiae. Bifunctional furocoumarins are about 20 times more effective in cell killing than Angelicin. Diploid cells are always more resistant than haploid cells. Dark repair (agar holding) increases survival. This effect can be at least in part correlated to the release of bound material from DNA in dark repair conditions. Bifunctional psoralens (10 μg/ml) are at least 10-fold more effective in inducing nuclear gene back mutations (his - to HIS + ) than Angelicin (10 μg/ml) plus 365 nm light or 254 nm ultraviolet light. In contrast cytoplasmic 'petite' (rho-) mutations are about as frequently induced by Angelicin plus 365 nm light as by 254 nm UV light. Bifunctional furocoumarins are less effective. The frequency of cytoplasmic 'petite' mutations per survivors decreases during dark repair conditions more efficiently after Angelicin than after Psoralen plus 365 nm light treatment. (orig.) [de

  19. Mutagenic Potential ofBos taurus Papillomavirus Type 1 E6 Recombinant Protein: First Description

    Directory of Open Access Journals (Sweden)

    Rodrigo Pinheiro Araldi

    2015-01-01

    Full Text Available Bovine papillomavirus (BPV is considered a useful model to study HPV oncogenic process. BPV interacts with the host chromatin, resulting in DNA damage, which is attributed to E5, E6, and E7 viral oncoproteins activity. However, the oncogenic mechanisms of BPV E6 oncoprotein per se remain unknown. This study aimed to evaluate the mutagenic potential of Bos taurus papillomavirus type 1 (BPV-1 E6 recombinant oncoprotein by the cytokinesis-block micronucleus assay (CBMNA and comet assay (CA. Peripheral blood samples of five calves were collected. Samples were subjected to molecular diagnosis, which did not reveal presence of BPV sequences. Samples were treated with 1 μg/mL of BPV-1 E6 oncoprotein and 50 μg/mL of cyclophosphamide (positive control. Negative controls were not submitted to any treatment. The samples were submitted to the CBMNA and CA. The results showed that BPV E6 oncoprotein induces clastogenesis per se, which is indicative of genomic instability. These results allowed better understanding the mechanism of cancer promotion associated with the BPV E6 oncoprotein and revealed that this oncoprotein can induce carcinogenesis per se. E6 recombinant oncoprotein has been suggested as a possible vaccine candidate. Results pointed out that BPV E6 recombinant oncoprotein modifications are required to use it as vaccine.

  20. Analysis of mutagenic DNA repair in a thermoconditional repair mutant of Saccharomyces cerevisiae. Pt. 2

    International Nuclear Information System (INIS)

    Siede, W.; Eckardt, F.; Brendel, M.

    1983-01-01

    The time course of REV2 dependent recovery from prelethal UV damage and UV-induced locus-specific reversion of the his5-2 allele was determined in temperature-shift experiments by use of a thermoconditional allele of the rev2 gene (rad5-8, rev2sup(ts)). In UV-irradiated, exponentially growing rev2sup(ts) cells the REV2 dependent repair acitivity persists for up to 8 h at permissive temperature (23 0 C), while the REV2 dependent mutagenic process is mostly completed within 2 h. The REV2 dependent process in exponentially growing cells is highly impaired by inhibition of protein synthesis. However, a REV2 dependent repair activity independent of de novo synthesis is detectable, even in the presence of up to 200 μg/ml cycloheximide, a response not found in stationary phase cells. Thus, the REV2 dependent process seems to be partially constitutive in exponentially growing cells. Additionally, exponentially growing rev2sup(ts) cells were considerably more UV-sensitive at restrictive temperature (36 0 C) than were stationary phase cells. (orig.)

  1. Mutagenic potential of water from Pelotas Creek in Rio Grande do Sul, Brazil.

    Science.gov (United States)

    Santos, T C O; Maciel, L F; Leal, K S; Bender, A E N; Paiva, T S; Garcias, G L; Martino-Roth, M G

    2009-09-01

    Water resource degradation is one of mankind's greatest worries, as it causes direct and indirect damage to the associated biota. We initiated a water monitoring study in Pelotas Creek in 2003 in order to assess the mutagenic effect of the creek's waters. Allium cepa cells exposed to water samples and a chronically exposed macrophyte were analyzed, through evaluation of the mitotic index, mitotic anomalies, interphase anomalies, and total anomalies. Five points were chosen along the lower course of Pelotas Creek, from which water samples and floating pennywort (Hydrocotyle ranunculoides, Apiaceae) were collected in 2006 and 2007. The enteric bacterium Escherichia coli was found at all sampling points; in the physical-chemical analysis, a few variables exceeded permitted limits, pH (from 6 to 9), chloride (250 mg/L), hardness (from 10 to 200 mg CaCO(3)/L), and conductivity (100 microOmega/cm). There was an increased number of cytogenetic anomalies in exposed A. cepa cells and in the pennywort in 2006 relative to 2007, which may be explained by the increased rainfall, which was three times greater in 2007 at some stations than in 2006.Omega/cm). There was an increased number of cytogenetic anomalies in exposed A. cepa cells and in the pennywort in 2006 relative to 2007, which may be explained by the increased rainfall, which was three times greater in 2007 at some stations than in 2006.

  2. Hispanic health disparities after a flood disaster: results of a population-based survey of individuals experiencing home site damage in El Paso (Texas, USA).

    Science.gov (United States)

    Collins, Timothy W; Jimenez, Anthony M; Grineski, Sara E

    2013-04-01

    In 2006, El Paso County, a predominantly Hispanic urban area, was affected by a flood disaster; 1,500 homes were damaged. We assessed the health impacts of the disaster upon 475 individuals whose homes were flood-damaged using mail survey data and logistic regression. Substantial proportions of individuals had one or more physical (43 %) or mental (18 %) health problem in the four months following the floods; 28 % had one or more injury or acute effect related to post-flood cleanup. Adverse event experiences, older age, and lower socioeconomic status were significantly associated with negative post-flood health outcomes in all three logistic regression models. A lack of access to healthcare, non-US citizenship, and English proficiency were significant predictors of negative outcomes in both the physical and mental health models, while Hispanic ethnicity (physical), native-birth (mental), and more serious home damage (cleanup) were significant predictors in one model each. The disaster had disproportionate negative health impacts on those who were more exposed, poorer, older, and with constrained resource-access. While a lack of US citizenship and Hispanic ethnicity were associated with higher risks, being less acculturated (i.e., English-deficient, foreign-born) may have protected against health impacts.

  3. Mutagenic and epigenetic influence of caffeine on the frequencies of UV-induced ouabain-resistant Chinese hamster cells

    International Nuclear Information System (INIS)

    Chang, Chia-Cheng; Philipps, C.; Trosko, J.E.; Hart, R.W.

    1977-01-01

    Caffeine, given as a post-treatment to UV-irradiated Chinese hamster cells in vitro, modified the frequency of induced mutations at the ouabain resistance locus. Mutation frequencies were increased when caffeine was added only for the DNA repair and mutation fixation period. When caffeine was added after the DNA repair and mutation fixation period, or immediately after DNA damage and for the entire repair and selection period, mutation frequencies were reduced. A hypothesis, given to explain both results, is that caffeine, by blocking a constitutive 'error-free' postreplication repair process, allows an 'error-prone' DNA repair process to produce many mutations. Moreover, caffeine, possibly by modifying C-AMP metabolism, causes a repression of induced mutations which, in effect, explains its anti-mutagenic and anti-carcinogenic properties

  4. Retroviral integration: Site matters

    Science.gov (United States)

    Demeulemeester, Jonas; De Rijck, Jan

    2015-01-01

    Here, we review genomic target site selection during retroviral integration as a multistep process in which specific biases are introduced at each level. The first asymmetries are introduced when the virus takes a specific route into the nucleus. Next, by co‐opting distinct host cofactors, the integration machinery is guided to particular chromatin contexts. As the viral integrase captures a local target nucleosome, specific contacts introduce fine‐grained biases in the integration site distribution. In vivo, the established population of proviruses is subject to both positive and negative selection, thereby continuously reshaping the integration site distribution. By affecting stochastic proviral expression as well as the mutagenic potential of the virus, integration site choice may be an inherent part of the evolutionary strategies used by different retroviruses to maximise reproductive success. PMID:26293289

  5. DNA Damage and Pulmonary Hypertension

    Science.gov (United States)

    Ranchoux, Benoît; Meloche, Jolyane; Paulin, Roxane; Boucherat, Olivier; Provencher, Steeve; Bonnet, Sébastien

    2016-01-01

    Pulmonary hypertension (PH) is defined by a mean pulmonary arterial pressure over 25 mmHg at rest and is diagnosed by right heart catheterization. Among the different groups of PH, pulmonary arterial hypertension (PAH) is characterized by a progressive obstruction of distal pulmonary arteries, related to endothelial cell dysfunction and vascular cell proliferation, which leads to an increased pulmonary vascular resistance, right ventricular hypertrophy, and right heart failure. Although the primary trigger of PAH remains unknown, oxidative stress and inflammation have been shown to play a key role in the development and progression of vascular remodeling. These factors are known to increase DNA damage that might favor the emergence of the proliferative and apoptosis-resistant phenotype observed in PAH vascular cells. High levels of DNA damage were reported to occur in PAH lungs and remodeled arteries as well as in animal models of PH. Moreover, recent studies have demonstrated that impaired DNA-response mechanisms may lead to an increased mutagen sensitivity in PAH patients. Finally, PAH was linked with decreased breast cancer 1 protein (BRCA1) and DNA topoisomerase 2-binding protein 1 (TopBP1) expression, both involved in maintaining genome integrity. This review aims to provide an overview of recent evidence of DNA damage and DNA repair deficiency and their implication in PAH pathogenesis. PMID:27338373

  6. Lethal and Mutagenic Effects of Tritium Decay Produced by Tritiated Compounds Incorporated into Bacteria and Bacteriophages

    Energy Technology Data Exchange (ETDEWEB)

    Person, S. [Pennsylvania State University, University Park, PA (United States)

    1968-06-15

    The work discussed below is predominantly from the author's laboratory. Some effects of tritium decay on bacteria and bacteriophages, using labelled compounds that are incorporated preferentially into DNA, RNA or protein, have been studied. A relatively high killing efficiency, the probability that a single decay produces loss of colony-forming ability in bacteria or loss of plaque-forming ability in bacteriophages, is observed for thymidine- methyl-{sup 3}H decay, but this is thought to be due to S-particle ionization damage. The most definitive experiments involved a comparison of killing efficiencies for decays originating as thymidine-methyl-{sup 3}H in phage DNA and as amino acid-{sup 3}H in phage protein with the calculated {beta}-particle path length through, the DNA in the two cases. Experimental and calculated values are essentially the same. Radiation-dose calculations to many different bacterial sub-volumes were determined for several different distributions of radioactivity. The high killing efficiency for thymidine-methyl- {sup 3}H decay can be explained by {beta}-particle ionizations, providing DNA is the sensitive target molecule and it is organized in a central volume of the cell (see also Ref.[24]). Although both the lethal and mutagenic effect of thymidine-methyl-{sup 3}H and amino acid-{sup 3}H decays can readily be explained on the basis of {beta}-particle ionizations, the observed large mutation frequency produced by uracil-5{sup 3}H decay cannot. The majority of mutations produced by uracil-5{sup 3}H decays are due to a specific chemical rearrangement of the parent molecule, since decays from uracil-6{sup 3}H are 6 to 7-fold less mutagenic. It is clear that the decays leading to mutations for cells labelled with uracil-5{sup 3}H originate as cytosine-5{sup 3}H in bacterial DNA. Recent work shows that the specific chemical rearrangement causes a C --> T(u) genetic coding change. (author)

  7. Combined anaerobic–ozonation process for treatment of textile wastewater: Removal of acute toxicity and mutagenicity

    Energy Technology Data Exchange (ETDEWEB)

    Punzi, Marisa, E-mail: marisa.punzi@biotek.lu.se [Department of Biotechnology, Lund University, P.O. Box 124, SE-221 00 Lund (Sweden); Nilsson, Filip [Water and Environmental Engineering at the Department of Chemical Engineering, Lund University, P.O. Box 124, SE-221 00 Lund (Sweden); Anbalagan, Anbarasan [Department of Biotechnology, Lund University, P.O. Box 124, SE-221 00 Lund (Sweden); Svensson, Britt-Marie [School of Education and Environment, Kristianstad University, SE-291 88 Kristianstad (Sweden); Jönsson, Karin [Water and Environmental Engineering at the Department of Chemical Engineering, Lund University, P.O. Box 124, SE-221 00 Lund (Sweden); Mattiasson, Bo; Jonstrup, Maria [Department of Biotechnology, Lund University, P.O. Box 124, SE-221 00 Lund (Sweden)

    2015-07-15

    Highlights: • COD and UV absorbance were effectively reduced. • The treated effluents were non-toxic to Artemia salina and Vibrio fischeri. • The real textile wastewater was mutagenic. • Mutagenicity persisted after bio treatment and even more after a short ozonation. • Higher ozone doses completely remove mutagenicity. - Abstract: A novel set up composed of an anaerobic biofilm reactor followed by ozonation was used for treatment of artificial and real textile effluents containing azo dyes. The biological treatment efficiently removed chemical oxygen demand and color. Ozonation further reduced the organic content of the effluents and was very important for the degradation of aromatic compounds, as shown by the reduction of UV absorbance. The acute toxicity toward Vibrio fischeri and the shrimp Artemia salina increased after the biological treatment. No toxicity was detected after ozonation with the exception of the synthetic effluent containing the highest concentration, 1 g/l, of the azo dye Remazol Red. Both untreated and biologically treated textile effluents were found to have mutagenic effects. The mutagenicity increased even further after 1 min of ozonation. No mutagenicity was however detected in the effluents subjected to longer exposure to ozone. The results of this study suggest that the use of ozonation as short post-treatment after a biological process can be beneficial for the degradation of recalcitrant compounds and the removal of toxicity of textile wastewater. However, monitoring of toxicity and especially mutagenicity is crucial and should always be used to assess the success of a treatment strategy.

  8. Mutagenicity of Tween 80-solvated mild gasification products in the Ames salmonella microsomal assay system

    Energy Technology Data Exchange (ETDEWEB)

    1992-01-13

    The results of the Tween 80-solvated Ames testing of six mild gasification samples indicate significant mutagenic activity only in the composite materials (MG-119 and MG-120), previously suspected from the DMSO-solvated assays, which had shown some variable but ultimately insignificant mutagenic responses. The activity of these samples from the Tween 80-solvated assays was quite low when compared to either the positive controls or the SRC-II HD coal-liquefaction reference material. The class of mutagenic activity expressed by these samples solvated in Tween 80 was that of an indirect-acting, frameshift mutagen(s) since significant activity was found only on tester strain TA98 in the presence of the metabolic activation fraction (S9). Because DMSO and other solvents have been shown to affect the mutagenic activity of certain pure chemicals, the possibility of solvent/mutagen interactions in complex mixtures such as coal-derived liquids exists. Thus, the testing of the genotoxic activity of undefined, chemically complex compounds may require the use of at least two solvent systems to reduce the possibility of artifactual findings. 10 refs., 4 tabs.

  9. Application of the Ames mutagenicity test to food processed by physical preservation methods

    International Nuclear Information System (INIS)

    Kooij, J.G. van; Leveling, H.B.; Schubert, J.

    1978-01-01

    An irradiated (380 krad) mixture of four fresh vegetables - leek, celery, carrot, and cauliflower - was examined for mutagenicity by the Ames mutagenicity test using four different histidine-deficient strains of Salmonellae. Water extracts were prepared from the irradiated and unirradiated vegetables - a freeze dried extract (FDE) and a boiled extract (BE). Several problems were overcome in the mutagenicity testing of a complex substance such as food which contains free histidine, different species of bacteria, and a mixture of low and high molecular weight chemicals. In addition, we eliminated an omission in the usual protocols of the Ames test by testing the positive mutagen controls in the presence and absence of the test samples, thus reducing the possible incidence of false negatives and false positives. The induction and expression of mutagenesis by sodium azide (SA) and ethidium bromide (EB) in TA 100 and TA 98 mutant strains, respectively, decreased with increasing amounts of FDE, while increasing levels of BE suppressed the number of revertants in TA 98 in the presence of EB, but exerted little influence on the mutagenicity of SA in TA 100. No difference was observed in the antimutagenic action between the irradiated and unirradiated vegetable extracts. Both the FDE and BE preparations suppressed the action of a frameshift mutagen, but with a base-pair mutagen only the FDE or uncooked vegetable extracts produced suppression. (author)

  10. Mutagenic effect of radiations of various LET on Salmonella cells

    International Nuclear Information System (INIS)

    Kozubek, S.; Krasavin, E.A.; Amirtaev, K.G.; Tokarova, B.; Basha, S.G.

    1989-01-01

    Regularities of mutagenic effect of heavy charged particles of helium, deuterium ions and protons on various strains of Salmonella typhimurium were studied. Linear dose dependences of mutation frequency in the range of low doses were revealed. A conclusion was made that mutation process at low dose irradiation is determined in various teststrains of Salmonella typhimurium by certain premutation injuries. Quite a different picture is observed in mutation process in case of high dose irradiation where effect of inducible SOS-repair is distinctly manifested. Not only spectra of primary DNA injuries but probability of their fixation into mutation can change with the increase of LET. If fixation probability doesn't change with LET increase for replicative mutagenesis which make basis contribution to linear component of dose dependence of mutation frequency the probability of fixation is increased for reparative mutagenesis. It accounts for increase of values of relative genetic efficiency with LET increase. 7 refs.; 6 figs.; 1 tab

  11. Mutagenic effects of space environment and protons on rice

    International Nuclear Information System (INIS)

    Wang Cailian; Chen Qiufang; Shen Mei

    1998-07-01

    Dry seeds of 5 rice varieties were carried by recoverable satellite for space mutation, and were irradiated by 4∼8 MeV protons with various doses. The mutagenic effects was studied. The results indicated that the space environment could cause chromosomal structure aberration and had stimulating mitosis action in root tip cells. As compared with γ-rays and protons, the effects of space environment flight were lower on chromosomal aberration but were significantly higher on mitosis index. Space environment and protons induce high frequency of chlorophyll deficient mutation and mutation in plant height and heading date in M 2 generation. Frequency of beneficial mutation induced by space environment and protons were higher than those induced by γ-rays

  12. Samplings of urban particulate matter for mutagenicity assays

    International Nuclear Information System (INIS)

    De Zaiacono, T.

    1996-07-01

    In the frame of a specific program relating to the evaluation of mutagenic activity of urban particulate matter, an experimental arrangement has been developed to sample aerosuspended particles from the external environment carried indoor by means of a fan. Instrumentation was placed directly in the air flow to minimize particle losses, and consisted of total filter, collecting particles without any size separation; cascade impactor, fractioning urban particulate to obtain separate samples for analyses; an optical device, for real time monitoring of aerosol concentration, temperature and relative humidity sensors. Some of the samples obtained were analysed to investigate: particle morphology, aerosol granulometric distributions, effect of relative humidity on collected particulate, amount of ponderal mass compared with real time optical determinations. The results obtained are reported here, together with some considerations about carbonaceous particles, in urban areas mainly originated from diesel exhausts, their degree of agglomeration and role to vehiculate substances into the human respiratory

  13. Survey of the mutagenicity of surface water, sediments, and drinking water from the Penobscot Indian Nation.

    Science.gov (United States)

    Warren, Sarah H; Claxton, Larry D; Diliberto, Janet; Hughes, Thomas J; Swank, Adam; Kusnierz, Daniel H; Marshall, Valerie; DeMarini, David M

    2015-02-01

    U.S. Environmental Protection Agency (US EPA) Regional Applied Research Effort (RARE) projects address the effects of environmental pollutants in a particular region on the health of the population in that region. This report is part of a RARE project that addresses this for the Penobscot Indian Nation (PIN), Penobscot Island, Maine, U.S., where the Penobscot River has had fish advisories for many years due to high levels of mercury. We used the Salmonella mutagenicity assay with strains TA100, TA98, YG1041, and YG1042 with and without metabolic activation to assess the mutagenic potencies of organic extracts of the Penobscot River water and sediment, as well as drinking-water samples, all collected by the PIN Department of Natural Resources. The source water for the PIN drinking water is gravel-packed groundwater wells adjacent to the Penobscot River. Most samples of all extracts were either not mutagenic or had low to moderate mutagenic potencies. The average mutagenic potencies (revertants/L-equivalent) were 337 for the drinking-water extracts and 177 for the river-water extracts; the average mutagenic potency for the river-sediment extracts was 244 revertants(g-equivalent)(-1). This part of the RARE project showed that extracts of the Penobscot River water and sediments and Penobscot drinking water have little to no mutagenic activity that might be due to the classes of compounds that the Salmonella mutagenicity assay detects, such as polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs (nitroarenes), and aromatic amines. This study is the first to examine the mutagenicity of environmental samples from a tribal nation in the U.S. Published by Elsevier Ltd.

  14. Heavy Metal-Induced Oxidative DNA Damage in Earthworms: A Review

    Directory of Open Access Journals (Sweden)

    Takeshi Hirano

    2010-01-01

    Full Text Available Earthworms can be used as a bio-indicator of metal contamination in soil, Earlier reports claimed the bioaccumulation of heavy metals in earthworm tissues, while the metal-induced mutagenicity reared in contaminated soils for long duration. But we examined the metal-induced mutagenicity in earthworms reared in metal containing culture beddings. In this experiment we observed the generation of 8-oxoguanine (8-oxo-Gua in earthworms exposed to cadmium and nickel in soil. 8-oxo-Gua is a major premutagenic form of oxidative DNA damage that induces GC-to-TA point mutations, leading to carcinogenesis.

  15. Vitamin C for DNA damage prevention

    International Nuclear Information System (INIS)

    Sram, Radim J.; Binkova, Blanka; Rossner, Pavel

    2012-01-01

    The ability of vitamin C to affect genetic damage was reviewed in human studies that used molecular epidemiology methods, including analysis of DNA adducts, DNA strand breakage (using the Comet assay), oxidative damage measured as levels of 8-oxo-7,8-dihydroxy-2′-deoxyguanosine (8-oxodG), cytogenetic analysis of chromosomal aberrations and micronuclei, and the induction of DNA repair proteins. The protective effect of vitamin C was observed at plasma levels > 50 μmol/l. Vitamin C supplementation decreased the frequency of chromosomal aberrations in groups with insufficient dietary intake who were occupationally exposed to mutagens, and also decreased the sensitivity to mutagens as assessed using the bleomycin assay. High vitamin C levels in plasma decreased the frequency of genomic translocations in groups exposed to ionizing radiation or c-PAHs in polluted air. The frequency of micronuclei was decreased by vitamin C supplementation in smokers challenged with γ-irradiation, and higher vitamin C levels in plasma counteracted the damage induced by air pollution. The prevalence of DNA adducts inversely correlated with vitamin C levels in groups environmentally exposed to high concentrations of c-PAHs. Increased vitamin C levels decreased DNA strand breakage induced by air pollution. Oxidative damage (8-oxodG levels) was decreased by vitamin C supplementation in groups with plasma levels > 50 μmol/l exposed to PM2.5 and c-PAHs. Modulation of DNA repair by vitamin C supplementation was observed both in poorly nourished subjects and in groups with vitamin C plasma levels > 50 μmol/l exposed to higher concentrations of c-PAHs. It is possible that the impact of vitamin C on DNA damage depends both on background values of vitamin C in the individual as well as on the level of exposure to xenobiotics or oxidative stress.

  16. Vitamin C for DNA damage prevention

    Energy Technology Data Exchange (ETDEWEB)

    Sram, Radim J., E-mail: sram@biomed.cas.cz [Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 14220 Prague 4 (Czech Republic); Binkova, Blanka; Rossner, Pavel [Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 14220 Prague 4 (Czech Republic)

    2012-05-01

    The ability of vitamin C to affect genetic damage was reviewed in human studies that used molecular epidemiology methods, including analysis of DNA adducts, DNA strand breakage (using the Comet assay), oxidative damage measured as levels of 8-oxo-7,8-dihydroxy-2 Prime -deoxyguanosine (8-oxodG), cytogenetic analysis of chromosomal aberrations and micronuclei, and the induction of DNA repair proteins. The protective effect of vitamin C was observed at plasma levels > 50 {mu}mol/l. Vitamin C supplementation decreased the frequency of chromosomal aberrations in groups with insufficient dietary intake who were occupationally exposed to mutagens, and also decreased the sensitivity to mutagens as assessed using the bleomycin assay. High vitamin C levels in plasma decreased the frequency of genomic translocations in groups exposed to ionizing radiation or c-PAHs in polluted air. The frequency of micronuclei was decreased by vitamin C supplementation in smokers challenged with {gamma}-irradiation, and higher vitamin C levels in plasma counteracted the damage induced by air pollution. The prevalence of DNA adducts inversely correlated with vitamin C levels in groups environmentally exposed to high concentrations of c-PAHs. Increased vitamin C levels decreased DNA strand breakage induced by air pollution. Oxidative damage (8-oxodG levels) was decreased by vitamin C supplementation in groups with plasma levels > 50 {mu}mol/l exposed to PM2.5 and c-PAHs. Modulation of DNA repair by vitamin C supplementation was observed both in poorly nourished subjects and in groups with vitamin C plasma levels > 50 {mu}mol/l exposed to higher concentrations of c-PAHs. It is possible that the impact of vitamin C on DNA damage depends both on background values of vitamin C in the individual as well as on the level of exposure to xenobiotics or oxidative stress.

  17. Antimutagenic properties of lactic acid-cultured milk on chemical and fecal mutagens

    Energy Technology Data Exchange (ETDEWEB)

    Hosono, A.; Kashina, T.; Kada, T.

    1986-09-01

    The antimutagenic properties of milk cultured with Lactobacillus bulgaricus and Streptococcus thermophilus were examined using streptomycin-dependent strains of Salmonella in an in vitro assay system. The mutagens utilized for testing included 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide, 4-nitroquinoline-N-oxide, and fecal mutagenic extracts from cats, monkeys, dogs and other mammals. Both types of cultured milk exhibited antimutagenic activity on all mutagens used. Antimutagenic activities of the cultured milks with 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide and 4-nitroquinoline-N-oxide increased with incubation time but were thermolabile beyond 55/sup 0/C for 10 min.

  18. Evaluation of the tickcide, genotoxic, and mutagenic effects of the Ruta graveolens L. (Rutaceae

    Directory of Open Access Journals (Sweden)

    Alessandra Vargas de Carvalho

    2015-10-01

    Full Text Available Current analysis investigated the tickcide effects of the aqueous extract and chloroform fractions of Ruta graveolens L. (rue on engorged females of Rhipicephalus microplus, as well as their genotoxic and mutagenic effects on human leukocytes. The best tickcide activity (non-dependent dose and genotoxic / mutagenic effects (dependent-dose were observed on exposure to chloroform fractions. Results suggest that extract fractions of R. graveolens L are efficient against R. microplus, although the fraction and the tested concentrations show genotoxic and mutagenic potential for human leukocytes.

  19. Reproductive health control of the families with mutagenic exposures after Chernobyl disaster

    International Nuclear Information System (INIS)

    Genyk-Berezovska, S.O.; Havrylyuk, Yu.Y.

    2003-01-01

    The aim of this work is to estimate the additional genetic risk (hazard) of mutagenic radiation for evacuated families in relatively ecologically favorable region. The reproductive characteristics, birth defects prevalence and antropometric data compare was held among newborns for 130 families before and after mutagenic exposure, when they were evacuated from radiation polluted region. The study results indicated no evidence of low-dose radiation exposure impact on realization of additional mutagenic burden in the liquidators and evacuees families through the extent of reproductive losses and CM

  20. Responses of physiological and biochemical components in Gossypium hirsutum L. to mutagens

    International Nuclear Information System (INIS)

    Muthusamy, A.; Vasanth, K.; Jayabalan, N.

    2003-01-01

    The two tetraploid varieties of cotton were exposed to gamma rays, EMS and SA. Chlorophyll, carotenoids, sugar, starch, free amino acids, protein, lipids, DNA and RNA were estimated quantitatively. All the physiological and biochemical components were increased in lower dose/concentration of the mutagenic treatments and they were decreased in higher dose/concentrations. The stimulation of the biochemical contents was a dose/concentration dependent response. Among the two varieties, MCU 11 was found to be responsive to mutagens than MCU 5. Based on the study the lower dose/concentration of the mutagenic treatments could enhance the biochemical components which is used for improved economic characters of cotton. (author)

  1. Comparative efficiency of chemical and radiation mutagens on two Cicer arietinum Rhizobial strains

    Energy Technology Data Exchange (ETDEWEB)

    Khare, A K; Shinde, D A; Nayak, M L [Jawaharlal Nehru Krishi Vishwa Vidyalaya, Indore (India)

    1982-03-01

    A comparison of efficacy due to chemical and radiation mutagens on morphology, nutritional totipotence and symbiotic character of two Cicer arietinum rhizobia has been made. The mutants produced as a result of radiations (gamma and UV rays) differed from parents in that, the mutant colony size was bigger and gelatinase activity was higher. The mutants were not deficient nutritionally, had wider host range and the size and number of nodules produced were higher. Radiation mutagenic effects were more pronounced than chemical mutagens. The mutants derived from chemicals were not as efficient as radiation mutants although they were better than parents in total nodulation.

  2. Histological and genetic studies on the male sterile mutants of tomato induced by gamma radiation and chemical mutagens

    Energy Technology Data Exchange (ETDEWEB)

    Choi, J K [Office of Rural Development, Suwon (Republic of Korea) Horticultural Experiment Station

    1976-03-01

    The object of this experiment was to test the radiosensitivity of the M/sub 1/ generation, and to determine the inheritance and morphological characteristics of the male-sterile mutants in tomatoes. The results obtained are as follows: Radiation damage varied with the water content of the seeds. The least damage occurred in the range of 11.34 to 14.29 percent moisture. Four tomato cultivars were gamma irradiated. The cultivar Sekai-ichi was the most sensitive while the other responded similarly to each other. Chemical mutagen treatments caused greater damage to germination, to delayed flowering and to pollen fertility than did radiation. Pollen fertility and seeds per fruit in seedling gamma irradiated plants decreased as the dosage and dose rate increased. Five male-sterile mutants were found. Each was controlled by a single recessive gene. All five male-steriles were nonallelic. Floral sized of the male-sterile mutants were slightly smaller. Ovule fertility varied, usually being lower than normal type. Male sterility varied, usually being lower than normal type. Male sterility in 109-1ms strain was caused by unbalanced, insufficient nutrients being made available to the pollen-mother cells from the tapetal tissued. (author).

  3. Molecular basis for the mutagenic and lethal effects of ultraviolet irradiation. Progress report, December 1, 1977--November 30, 1978

    International Nuclear Information System (INIS)

    Grossman, L.

    1978-07-01

    Our earlier work on the chemical basis of mutagenesis led to certain chemical generalities necessary to explain how certain mutagens such as UV light and hydroxylamine functioned in information transfer systems (replicative, transcriptive and translational). When such modifications were applied to biologically active DNA in a controlled manner biological expression was non-stoichiometric because much of the damage was removed from the DNA by repair systems. Our efforts were then directed to these systems which led to: the isolation, purification and characterization of endonucleases responsible for the first and controlling step in DNA repair referred to as incision in both M. luteus and E. coli; the isolation, purification and characterization of exonucleases responsible for the removal or excision of damaged nucleotides in M. luteus and human placental trophoblasts; the repair of UV damaged biologically active transforming and transfecting DNAs by purified endonucleases, exonucleases, DNA polymerase I and polynucleotide ligase from M. luteus and E. coli; the characterization of the dual gene control for incision phenomenon in M. luteus and E. coli; and isolation, purification and characterization of repair enzymes from human placenta

  4. Metabolic activation of polycyclic and heterocyclic aromatic hydrocarbons and DNA damage: A review

    International Nuclear Information System (INIS)

    Xue Weiling; Warshawsky, David

    2005-01-01

    Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic compounds (HACs) constitute a major class of chemical carcinogens present in the environment. These compounds require activation to electrophilic metabolites to exert their mutagenic or carcinogenic effects. There are three principal pathways currently proposed for metabolic activation of PAH and HAC: the pathway via bay region dihydrodiol epoxide by cytochrome P450 enzymes (CYPs), the pathway via radical cation by one-electron oxidation, and the ortho-quinone pathway by dihydrodiol dehydrogenase (DD). In addition to these major pathways, a brief description of a minor metabolic activation pathway, sulfonation, for PAHs that contain a primary benzylic alcoholic group or secondary hydroxyl group(s) is included in this review. The DNA damages caused through the reactive metabolites of PAH/HAC are described involving the DNA covalent binding to form stable or depurinating adducts, the formation of apurinic sites, and the oxidative damage. The review emphasizes the chemical/biochemical reactions involved in the metabolic processes and the chemical structures of metabolites and DNA adducts

  5. Evaluation of mutagenic potential of contaminated atmosphere at Ibirapuera Park, Sao Paulo - SP, Brazil, using the Tradescantia stamen-hair assay

    International Nuclear Information System (INIS)

    Ferreira, Maria Izildinha; Domingos, Marisa; Gomes, Heliana de A; Saldiva, Paulo H.N.; Assuncao, Joao V. de

    2007-01-01

    Trad-SHM assay was used to check mutagenic potential of atmospheric contamination at Ibirapuera Park, located in Sao Paulo city, Brazil, and variation of risk along the year, besides determining which Tradescantia clone, BNL 4430 or KU-20, better indicates risk. Thirty pots of both clones were exposed during one-year period (September, 2002-August, 2003). Twenty inflorescences were taken from each clone twice a month in the morning, in order to estimate the frequency of mutations in stamen hairs. Results were compared to air pollution and climatic data measured next to the exposure site. KU-20 showed stamen-hair mutations greater than BNL 4430. Greatest mutation rates in KU-20 were observed in condition of high monthly mean of NO 2 and average peak concentrations of NO during the day, indicating that mutagenic effects originated from vehicular pollution. Clone KU-20 revealed to be more appropriate for biomonitoring purposes at the Park. - Clone KU-20 showed to be more appropriate than clone BNL 4430 to indicate vehicular pollution mutagenic risks in Trad-SHM assay

  6. The C-terminal region of Rad52 is essential for Rad52 nuclear and nucleolar localization, and accumulation at DNA damage sites immediately after irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Koike, Manabu, E-mail: m_koike@nirs.go.jp [DNA Repair Gene Res., National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Yutoku, Yasutomo [DNA Repair Gene Res., National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Graduate School of Science, Chiba University, Yayoicho, Inage-ku, Chiba 263-8522 (Japan); Koike, Aki [DNA Repair Gene Res., National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2013-05-31

    Highlights: •Rad52 might play a key role in the repair of DSB immediately after irradiation. •EYFP-Rad52 accumulates rapidly at DSB sites and colocalizes with Ku80. •Accumulation of Rad52 at DSB sites is independent of the core NHEJ factors. •Localization and recruitment of Rad52 to DSB sites are dependent on the Rad52 CTR. •Basic amino acids in Rad52 CTR are highly conserved among vertebrate species. -- Abstract: Rad52 plays essential roles in homologous recombination (HR) and repair of DNA double-strand breaks (DSBs) in Saccharomyces cerevisiae. However, in vertebrates, knockouts of the Rad52 gene show no hypersensitivity to agents that induce DSBs. Rad52 localizes in the nucleus and forms foci at a late stage following irradiation. Ku70 and Ku80, which play an essential role in nonhomologous DNA-end-joining (NHEJ), are essential for the accumulation of other core NHEJ factors, e.g., XRCC4, and a HR-related factor, e.g., BRCA1. Here, we show that the subcellular localization of EYFP-Rad52(1–418) changes dynamically during the cell cycle. In addition, EYFP-Rad52(1–418) accumulates rapidly at microirradiated sites and colocalizes with the DSB sensor protein Ku80. Moreover, the accumulation of EYFP-Rad52(1–418) at DSB sites is independent of the core NHEJ factors, i.e., Ku80 and XRCC4. Furthermore, we observed that EYFP-Rad52(1–418) localizes in nucleoli in CHO-K1 cells and XRCC4-deficient cells, but not in Ku80-deficient cells. We also found that Rad52 nuclear localization, nucleolar localization, and accumulation at DSB sites are dependent on eight amino acids (411–418) at the end of the C-terminal region of Rad52 (Rad52 CTR). Furthermore, basic amino acids on Rad52 CTR are highly conserved among mammalian, avian, and fish homologues, suggesting that Rad52 CTR is important for the regulation and function of Rad52 in vertebrates. These findings also suggest that the mechanism underlying the regulation of subcellular localization of Rad52 is

  7. UV-B damage amplified by transposons in maize

    International Nuclear Information System (INIS)

    Walbot, V.

    1999-01-01

    While absorbing visible light energy for photosynthesis, plants are unavoidably exposed to ultraviolet radiation, which is particularly harmful at shorter wavelengths (UV-B radiation). Ozone depletion in the atmosphere means that plants receive episodic or steadily increasing doses of UV-B, which damages their photosynthetic reaction centres, crosslinks cellular proteins, and induces mutagenic DNA lesions. Plant adaptive mechanisms of shielding and repair are therefore critical to survival — for example, somatic tissues of maize and Arabidopsis defective in phenolic sunscreen pigments incur increased DNA damage, and mutants defective in DNA repair are killed by UV-B

  8. The dependence of natural regeneration of forest trees on upper soil conditions and acidity at damaged sites in the Black Forest, Germany

    International Nuclear Information System (INIS)

    Littek, T.

    1993-06-01

    It was the goal of this study to investigate the influence of different upper soil conditions on the germination and establishment, as well as the growth, of young plants of various tree species. For this purpose, four test plots in the region of the Black Forest were laid out, in which, by various means of site preparation and fertilization, the upper soils were changed. Natural seeding of common spruce, European silver-fir, beech, sycamore maple, European mountainash, and grey alder was simulated by means of controlled sowing. For comparison, a greenhouse experiment was carried out, examining the germination and development of the same tree species in various soil substrata, using different fertilizers, and under the influence of artificial acid rain. The most important results - with a high level of variation depending on the tree species examined - can be summarized as follows: Based on the results of field and greenhouse experiments, as well as on the investigations of other authors, it can be concluded that natural regeneration of forest stands is considerably impeded under conditions of increasing soil acidity and by high acid depositions. This is seen directly as the result of unfavorable chemical conditions in the upper soil, as well as indirectly due to deteriorating competitiveness against other vegetation. Site preparation and lime or dolomite fertilization can be important measures in the practice of forestry, to encourage natural regeneration in highly acidic sites with an unfavourable humus layer and a high presence of competing vegetation. (orig./UWA). 2 figs., 85 tabs., 269 refs [de

  9. After facial nerve damage, regenerating axons become aberrant throughout the length of the nerve and not only at the site of the lesion: an experimental study.

    Science.gov (United States)

    Choi, D; Raisman, G

    2004-02-01

    After facial nerve trauma, aberrant regeneration is associated with synkinesis. Animal models of mechanical nerve guides or reparative cell transplants at the site of a lesion have not been shown to improve disorganized regeneration. We examined whether this is because regenerating axons become disorganized throughout the length of the nerve and not only at the site of the lesion. In rats (n = 12), retrograde fluorescent tracer techniques were used to establish that most of the temporal branch fibres were carried in the superior half of the facial nerve trunk. In two further groups of rats (n = 24) a complete proximal facial nerve lesion was made, and the nerve immediately repaired by suture. After 4 weeks, at a second operation, the superior half of the facial nerve trunk was cut, either proximal or distal to the original lesion, and retrograde tracers were applied to distal branches of the nerve. It was possible to localize the points at which regenerating fibres became aberrant in their course by studying the number of labelled motoneurons in the facial nucleus after application of the tracer to the temporal branch of the nerve: this was similar in the distal and proximal hemisection groups, suggesting that aberrant axonal development occurred throughout the length of the nerve. Future strategies aimed at improving the organization of regeneration need to provide guidance cues not only at the site of the lesion as previously thought, but also throughout the length of the nerve.

  10. Amelioration of the cyclophosphamide induced genotoxic damage in mice by the ethanolic extract of Equisetum arvense.

    Science.gov (United States)

    Kour, Jasbir; Ali, Md Niamat; Ganaie, Hilal Ahmad; Tabassum, Nahida

    2017-01-01

    In the present study, we evaluated the potential of the plant E. arvense against the cytotoxic and mutagenic effects induced by cyclophosphamide (chemotherapeutic agent) in the bone marrow cells of mice using the Chromosome assay (CA) and Mitotic index (MI) in vivo as the biomarkers. The study was performed following 3 protocols: pre-treatment, simultaneous treatment and post-treatment with the ethanolic extract of the plant. The results demonstrated that the plant extract was not cytotoxic and mutagenic and has a protective effect against the mutagenicity induced by cyclophosphamide in pre, simultaneous and post treatments and against its cytotoxicity as well. Because of its ability to prevent chromosomal damage , E. arvense is likely to open an interesting field concerning its possible use in clinical applications, most importantly in cancer as a chemopreventive agent or even as a coadjuvant to chemotherapy to reduce the side effects associated with it.

  11. Cytotoxicity and mutagenicity of opthalmic solution preservatives and UVA radiation in L5178Y cells

    International Nuclear Information System (INIS)

    Withrow, T.J.; Brown, N.T.; Hitchins, V.M.; Strickland, A.G.

    1989-01-01

    Four preservatives used in ophthalmic solutions were tested for toxic and mutagenic potential in mouse lymphoma cells with and without exposure of cells to ultraviolet A (UVA) radiation. The preservatives tested were benzalkonium chloride (BAK), chlorhexidine, thimerosal and ethylenediaminetetraacetic acid (EDTA). Cell survival and mutagenesis were measured using the L5178Y mouse lymphoma (TK +/- ) system. Cells were exposed to varying amounts of preservatives for 1 h at 37 0 C, and aliquots irradiated with UVA radiation (during exposure to preservative). Cells were then assayed for survival, and mutagenesis at the thymidine kinase (TK) locus. In concentrations commonly found in ophthalmic solutions, BAK, chlorhexidine, and thimerosal were toxic to cells, and thimerosal was slightly mutagenic. When cells were exposed to preservative and UVA radiation, chlorhexidine was mutagenic and the mutagenic activity of thimerosal was enhanced. (author)

  12. The effect of γ-radiation on smoked fish using short-term mutagenicity assays

    International Nuclear Information System (INIS)

    Dela Rosa, A.M.; Banzon, R.B.

    1989-01-01

    The effect of γ-radiation on the mutagenicity potential of wood-smoked fish was investigated. Smoked fish were irradiated with radiation doses of 2.0, 4.0, 6.0 and 8.0 kGy. The DMSO extracts of non-radiated and irradiated smoked fish were tested for mutagenicity using the Ames plate incorporation assay, host-mediated assay, and the micronucleus test. It was observed that γ-irradiation did not induce any significant increase in the number of revertants of TA98, TA100 and TA104 as compared with the non-radiated smoked fish. Results of the host-mediated assay and the micronucleus test showed no difference in the mutagenic response of non-radiated in irradiated smoked fish. The results indicate thet γ-radiation does not introduce mutagens in smoked fish. (author). 17 refs.; 6 tabs

  13. Study on mutagenic and toxic compounds in lake water used as drinking water supply

    International Nuclear Information System (INIS)

    Monarca, S.; Zanardini, A.

    1996-01-01

    Trace amounts of mutagenic and toxic substances are frequently found in drinking water, causing a great concern for their potential health effects. Aim of this work is to develop a reliable and efficient screening method for detecting aquatic mutagens and toxins in surface water used for human consumption. For this purpose different methods of concentration of lake water have been experimented by using three different solid phase extraction systems at different pHs and studying the adsorbates by means of a mutagenicity test (Ames test), a toxicity test (LUMIStox) and chemical analysis (GC,MS). This integrated chemical/biological approach showed to be a suitable system for the preliminary choice of an efficient screening method for aquatic mutagens and toxins and to give useful data for the evaluation of potential health hazards

  14. Cytotoxicity and mutagenicity of opthalmic solution preservatives and UVA radiation in L5178Y cells

    Energy Technology Data Exchange (ETDEWEB)

    Withrow, T.J.; Brown, N.T.; Hitchins, V.M.; Strickland, A.G. (Food and Drug Administration, Rockville, MD (USA). Center for Devices and Radiological Health)

    1989-09-01

    Four preservatives used in ophthalmic solutions were tested for toxic and mutagenic potential in mouse lymphoma cells with and without exposure of cells to ultraviolet A (UVA) radiation. The preservatives tested were benzalkonium chloride (BAK), chlorhexidine, thimerosal and ethylenediaminetetraacetic acid (EDTA). Cell survival and mutagenesis were measured using the L5178Y mouse lymphoma (TK{sup +/-}) system. Cells were exposed to varying amounts of preservatives for 1 h at 37{sup 0}C, and aliquots irradiated with UVA radiation (during exposure to preservative). Cells were then assayed for survival, and mutagenesis at the thymidine kinase (TK) locus. In concentrations commonly found in ophthalmic solutions, BAK, chlorhexidine, and thimerosal were toxic to cells, and thimerosal was slightly mutagenic. When cells were exposed to preservative and UVA radiation, chlorhexidine was mutagenic and the mutagenic activity of thimerosal was enhanced. (author).

  15. Predictive Models for Carcinogenicity and Mutagenicity: Frameworks,State-of-the-Art, and Perspectives

    Science.gov (United States)

    Mutagenicity and carcinogenicity are endpoints of major environmental and regulatory concern. These endpoints are also important targets for development of alternative methods for screening and prediction due to the large number of chemicals of potential concern and the tremendou...

  16. An approach to quantitate and control the mutagenic hazards of environmental chemical and radioactive pollutants

    International Nuclear Information System (INIS)

    Murthy, M.S.S.

    1977-01-01

    Human population, both at the occupational and non-occupational levels, is exposed to the environment polluted by man-made chemicals and radiation sources. The parameters required for quantitating mutagenic hazards of any agent are listed and it has been pointed out that though sufficient information of this nature is available in the case of radiations, it is almost impossible to collect similar information for chemical substances due to their number running into astronomical figures. A short-cut approach, therefore, is suggested to quantitate and control the mutagenic hazards of these pollutants. It is to express the mutagenic hazards of a chemical substance in terms of equivalent radiation units. The unit proposed for this purpose is called as Rem-Equivalent Chemical (REC). Total mutagenic burden to the society should take account of exposure from both chemicals and radiations. Advantages and limitation of this approach are discussed. (M.G.B.)

  17. Improved mutagen-testing systems in mice. Progress report, 1 June 1975--31 May 1976

    International Nuclear Information System (INIS)

    Roderick, T.H.

    1976-01-01

    Progress is reported on the following research projects: detection of inversions; inversions produced by chemical mutagens and x radiation; phenotypic effects of inversions; linkage of inversions; cytology of inversions; Robertsonian metacentric translocations; and somatic crossing-over in mammals

  18. Analysis of Hexanitrostilbene (HNS) and Dipicryethane (DPE) for Mutagenicity by the Ames/Salmonella Assay

    Energy Technology Data Exchange (ETDEWEB)

    Wu, R; Felton, J

    2007-10-12

    The Ames/Salmonella assay, developed by Professor Bruce Ames at the University of California, Berkeley, is a rapid and sensitive assay for detecting mutagenicity of various chemical compounds (Maron and Ames, 1983). It is a widely accepted short-term assay for detecting chemicals that induce mutations in the histidine (his) gene of Salmonella typhimurium. This is a reverse mutation assay that detects the mutational reversion of his-dependent Salmonella to the his-independent counterpart. Thereby, mutagenic compounds will increase the frequency of occurrence of his-independent bacterial colonies. The assay utilizes the specific genetically constructed strains of bacteria either with or without mammalian metabolic activation enzymes (S9), Aroclor induced rat liver homogenate to assess the mutagenicity of different compounds. In this study, we will use the Ames/Salmonella assay to investigate the mutagenicity of Hexanitrostilbene (HNS) from both Bofors and Pantex, and Dipicryethane (DPE).

  19. Mutagen Sensitivity, Apoptosis, and Polymorphism in DNA Repair as Measures of Prostate Cancer Risk

    National Research Council Canada - National Science Library

    Goldman, Radoslav

    2006-01-01

    .... We also created a computerized database of the samples in Microsoft Access. We developed assays for mutagen sensitivity, comet assay, and apoptosis in white blood cells exposed to bleomycin and ionizing radiation to evaluate...

  20. SERIES: Genomic instability in cancer Balancing repair and tolerance of DNA damage caused by alkylating agents

    Science.gov (United States)

    Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D

    2013-01-01

    Alkylating agents comprise a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER), and mismatch repair (MMR) respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for an organism's favorable response to alkylating agents. Furthermore, an individual's response to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity. PMID:22237395

  1. Health effects of soy-biodiesel emissions: mutagenicity-emission factors.

    Science.gov (United States)

    Mutlu, Esra; Warren, Sarah H; Matthews, Peggy P; King, Charly; Walsh, Leon; Kligerman, Andrew D; Schmid, Judith E; Janek, Daniel; Kooter, Ingeborg M; Linak, William P; Gilmour, M Ian; DeMarini, David M

    2015-01-01

    Soy biodiesel is the predominant biodiesel fuel used in the USA, but only a few, frequently conflicting studies have examined the potential health effects of its emissions. We combusted petroleum diesel (B0) and fuels with increasing percentages of soy methyl esters (B20, B50 and B100) and determined the mutagenicity-emission factors expressed as revertants/megajoule of thermal energy consumed (rev/MJ(th)). We combusted each fuel in replicate in a small (4.3-kW) diesel engine without emission controls at a constant load, extracted organics from the particles with dichloromethane, determined the percentage of extractable organic material (EOM), and evaluated these extracts for mutagenicity in 16 strains/S9 combinations of Salmonella. Mutagenic potencies of the EOM did not differ significantly between replicate experiments for B0 and B100 but did for B20 and B50. B0 had the highest rev/MJ(th), and those of B20 and B100 were 50% and ∼85% lower, respectively, in strains that detect mutagenicity due to polycyclic aromatic hydrocarbons (PAHs), nitroarenes, aromatic amines or oxidative mutagens. For all strains, the rev/MJ(th) decreased with increasing biodiesel in the fuel. The emission factor for the 16 EPA Priority PAHs correlated strongly (r(2 )= 0.69) with the mutagenicity-emission factor in strain TA100 + S9, which detects PAHs. Under a constant load, soy-biodiesel emissions were 50-85% less mutagenic than those of petroleum diesel. Without additional emission controls, petroleum and biodiesel fuels had mutagenicity-emission factors between those of large utility-scale combustors (e.g. natural gas, coal, or oil) and inefficient open-burning (e.g. residential wood fireplaces).

  2. Mutagenic and genotoxic activity of particulate matter MP2,5, in Pamplona, North Santander, Colombia

    OpenAIRE

    Martínez Montañez, Mónica Liseth; Meléndez Gélvez, Iván; Quijano Parra, Alfonso

    2012-01-01

    Objective: To study the mutagenic and genotoxic activities of particulate material (MP2,5 collected in Pamplona, Norte de Santander, Colombia.Materials and methods: MP2,5 was monitored by means of a Partisol 2025 sequential air sampler with Plus Palmflex quartz filters. The latter were subjected to two extraction procedures: Soxhlet extraction using dichloromethane-acetone; and ultrasonic extraction using dichloromethane, acetone and dichloromethane/ acetone mix. The mutagenic and genotoxic a...

  3. Microplate Ames MPF™ test use in assessment of mutagenic properties of dust pollution

    Directory of Open Access Journals (Sweden)

    Agnieszka Kozłowska

    2012-09-01

    Full Text Available Background: Highly industrialized Upper Silesia Region is particularly polluted by both anthropogenic and natural airborne particulate matters, which may lead to negative health effects in human. Materials and methods: The aim of the study was to assess the mutagenic properties of dust extracts which were collected in six cities in the Silesian Voivodeship. Dust samples were collected on glass fiber filters by the aspirator with air flow ca. 1 m3/min. Extraction of pollution was carried out using dichlorometane. The extracted samples were dissolved in dimethylsulfoxide (DMSO. The mutagenic properties were assessed using microplate Ames assay MPFTM with the use of bacteria Salmonella typhimurium strain TA98 and TA100. Results: In microplate Ames assay MPFTM there was observed a linear dose-response relationship in both metabolic variants of TA98 strain. Similar relationship was observed for TA100 strain with metabolic activation (S9. Mutagenic activity (AM of 100% extracts for TA98 strain in both metabolic variants (S9 exceeded 2, what indicate highly mutagenic effects of dust extracts. There was no mutagenic activity observed in the assay with TA100 (S9, AM 1. In the variant with exogenous metabolic activation (S9 in TA100 strain AM values ranged from AM1,160,15 to AM9,671,02. Mutagenic activity varied between different cities. Conclusions: The study demonstrated that microplate Ames assay MPFTM is fast and complex method of assessing the mutagenic properties of dust pollution, which exert toxic effect on organisms. The use of microplate Ames assay MPFTM together with chemical analyses of air dust pollution may evaluate the level of exposure in the environment and enable to perform health risk assessment in populations exposed to mutagenic, toxic and cytotoxic substances.

  4. Updated synthesis of knowledge related to the impact of radioactive releases from the damaged nuclear site of Fukushima Dai-Ichi on the marine environment - 13 July 2012

    International Nuclear Information System (INIS)

    2012-01-01

    Illustrated by tables, figures and graphs, this report first comments the evolution of the radioactive pollution of sea water: main radionuclides notices in sea water since the 21 March 2011 (with two main origins: atmospheric fallouts, liquid releases from the site), evolution of sea water contamination along the coast at the vicinity of the power station, simulation of caesium 137 dispersion in sea water off Japan. Then, it comments the evolution of the presence of radionuclides in sediments and in marine species (species with contamination level exceeding the admissible level for consumption, concentrations noticed by sea animals, expected evolution for marine species, other published data)

  5. A descriptive mutagenicity assessment of tretinoin in Allium sativum

    International Nuclear Information System (INIS)

    Dela Llana, Jonamine M.; Reyes, Florence C.

    1999-01-01

    This paper is primarily designed to assess the mutagenicity of tretinoin by applying the Allium test. Furthermore, it has the following objectives: to evaluate the macroscopic abnormalities caused by tretinoin based on root length and root form parameters; to investigate whether tretinoin can induce aberrances in cell division such as the formation of micronucleus, anaphase bridges, early anaphase, C-metaphase, sticky chromosome, stretched chromosome, vagrant chromosome and precocious chromosome; to determine the variation in the aberrations in the different concentration of tretinoin. Procedure: eight hundred equal-sized garlic bulbs were immersed in various concentrations of tretinoin and in tap water as control. These were divided into two groups. Six hundred bulbs were evaluated for macroscopic parameters while the remaining two hundred bulbs were fixed for microscopic observations. The Allium test set-ups were placed in the plant laboratory of UP-Manila. The were harvested on the third and on the fifth day. The fixed roots were examined in the Cytogenetics Laboratory of the Philippine Nuclear Research Institute. The data gathered for macroscopic parameter was statistically tested using Complete Randomized Design and the Tukey's Honestly Significant Difference. The microscopic abnormalities were determined descriptively for every concentration. Findings: analysis of macroscopic and microscopic parameters showed that: according to the analyses of variances, the number of roots, the root length and the number of root forms such as straight, bent, bulbous and tapered were not equal in all concentrations. However, the difference in the number of curled roots was not significant.; the root length distinctly showed the toxicity effect of tretinoin. The growth or the length of roots decreases as the tretinoin concentration increases; the mitotic abnormalities observed in the garlic cells include micronucleus, anaphase bridges, early anaphase. C-metaphase, sticky

  6. A descriptive mutagenicity assessment of tretinoin in Allium sativum

    Energy Technology Data Exchange (ETDEWEB)

    Dela Llana, Jonamine M; Reyes, Florence C

    1999-07-01

    This paper is primarily designed to assess the mutagenicity of tretinoin by applying the Allium test. Furthermore, it has the following objectives: to evaluate the macroscopic abnormalities caused by tretinoin based on root length and root form parameters; to investigate whether tretinoin can induce aberrances in cell division such as the formation of micronucleus, anaphase bridges, early anaphase, C-metaphase, sticky chromosome, stretched chromosome, vagrant chromosome and precocious chromosome; to determine the variation in the aberrations in the different concentration of tretinoin. Procedure: eight hundred equal-sized garlic bulbs were immersed in various concentrations of tretinoin and in tap water as control. These were divided into two groups. Six hundred bulbs were evaluated for macroscopic parameters while the remaining two hundred bulbs were fixed for microscopic observations. The Allium test set-ups were placed in the plant laboratory of UP-Manila. The were harvested on the third and on the fifth day. The fixed roots were examined in the Cytogenetics Laboratory of the Philippine Nuclear Research Institute. The data gathered for macroscopic parameter was statistically tested using Complete Randomized Design and the Tukey's Honestly Significant Difference. The microscopic abnormalities were determined descriptively for every concentration. Findings: analysis of macroscopic and microscopic parameters showed that: according to the analyses of variances, the number of roots, the root length and the number of root forms such as straight, bent, bulbous and tapered were not equal in all concentrations. However, the difference in the number of curled roots was not significant.; the root length distinctly showed the toxicity effect of tretinoin. The growth or the length of roots decreases as the tretinoin concentration increases; the mitotic abnormalities observed in the garlic cells include micronucleus, anaphase bridges, early anaphase. C-metaphase, sticky

  7. Structural features of nitroaromatics that determine mutagenic activity in Salmonella typhimurium

    International Nuclear Information System (INIS)

    Vance, W.A.; Levin, D.E.

    1984-01-01

    Seventeen structurally homologous nitroaromatics were tested for direct-acting mutagenic potency in nine strains of Salmonella typhimurium. The following four structural features were determined to have a strong influence on mutagenic activity: physical dimensions of the aromatic rings, isomeric position of the nitro group, conformation of the nitro group with respect to the plane of the aromatic rings, and ability to resonance-stabilize the utimate electrophile. Progressive addition of five- and six-membered rings to a nitrobenzene nucleus demonstrated that mutagenic activity was a direct function of size. Nitroaromatics with a nitro group oriented along the long axis of symmetry of the molecule were more potent mutagens that those with the nitro group oriented along the short axis. These results are discussed in light of the insertion-denaturation model for intercalation of certain DNA adducts. Finally, structural features that contribute to resonance stabilization of the reactive nitrenium ion enhance mutagenic potency. The predictive value of these structure-activity relationships should permit a first approximation in the assessment of mutagenic potency of nitroaromatics

  8. Intramolecular tautomerisation and the conformational variability of some classical mutagens – cytosine derivatives: quantum chemical study

    Directory of Open Access Journals (Sweden)

    Hovorun D. M.

    2011-04-01

    Full Text Available Aim. To determine the lifetime of the mutagenic cytosine derivatives through the investigation of the physicochemical mechanisms of their intramolecular proton transfer. Methods. Non-empirical quantum chemistry, the analysis of the electron density by means of Bader’s atoms in molecules (AIM theory and physicochemical kinetics were used. Results. It is shown that the modification of all investigated compounds, except DCyt, prevents their pairing in both mutagenic and canonical tautomeric forms with a base which is an interacting partner. This effect can inhibit their mutagenic potential. It is also established that Watson-Crick tautomeric hypothesis can be formally expanded for the investigated molecules so far as a lifetime of the mutagenic tautomers much more exceeds characteristic time for the incorporation of one nucleotides pair by DNA biosynthesis machinery. It seems that just within the frame of this hypothesis it will be possible to give an adequate explanation of the mechanisms of mutagenic action of N4-aminocytosine, N4-methoxycytosine, N4-hydroxycytosine and N4dehydrocytosine, which have much more energy advantageous imino form in comparison with amino form. Conclusions. For the first time the comprehensive conformational analysis of a number of classical mutagens, namely cytosine derivatives, has been performed using the methods of non-empirical quantum chemistry at the MP2/6-311++G (2df,pd//B3LYP/6-311++G(d,p level of theory

  9. Assessment of the mutagenic potential of cyanobacterial extracts and pure cyanotoxins.

    Science.gov (United States)

    Sieroslawska, Anna

    2013-11-01

    The aim of the study was to assess the mutagenic potential of extracts obtained from the cyanobacterial bloom-forming cells harvested from the water body located in Lubelszczyzna region of southeastern Poland. Three cyanotoxins, microcystin-LR, cylindrospermopsin and anatoxin-a were detected in some of the studied samples in different concentrations. All extracts were assessed for their potential mutagenic effects with the use of a short-term bacterial assay, the Ames test. Mutagenic activity was observed in four of all ten studied extracts, mainly toward the Salmonella typhimurium TA100 strain. On the contrary, the cyanotoxins in purified forms occurred not to be mutagenic or cytotoxic towards S. typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2 uvrA and WP2 [pKM101] up to a concentration of 10 μg/ml. Similarly, there were no effects after bacteria exposure to the mixture of purified toxins. It has been also detected that after fractionation, genotoxic impact of previously mutagenic extracts was weaker and the highest potency in revertant induction possessed fractions containing very hydrophilic compounds. The results indicate, that while tested cyanotoxins were not directly responsible for the observed mutagenicity of the extracts analysed, some synergistic interactions with other unidentified cyanobacterial-derived factors involved in the process are possible. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Mutagenic atmospheres resulting from the photooxidation of aromatic hydrocarbon and NOx mixtures

    Science.gov (United States)

    Riedel, Theran P.; DeMarini, David M.; Zavala, Jose; Warren, Sarah H.; Corse, Eric W.; Offenberg, John H.; Kleindienst, Tadeusz E.; Lewandowski, Michael

    2018-04-01

    Although many volatile organic compounds (VOCs) are regulated to limit air pollution and the consequent health effects, the photooxidation products generally are not. Thus, we examined the mutagenicity in Salmonella TA100 of photochemical atmospheres generated in a steady-state atmospheric simulation chamber by irradiating mixtures of single aromatic VOCs, NOx, and ammonium sulfate seed aerosol in air. The 10 VOCs examined were benzene; toluene; ethylbenzene; o-, m-, and p-xylene; 1,2,4- and 1,3,5-trimethylbenzene; m-cresol; and naphthalene. Salmonella were exposed at the air-agar interface to the generated atmospheres for 1, 2, 4, 8, or 16 h. Dark-control exposures produced non-mutagenic atmospheres, illustrating that the gas-phase precursor VOCs were not mutagenic at the concentrations tested. Under irradiation, all but m-cresol and naphthalene produced mutagenic atmospheres, with potencies ranging from 2.0 (p-xylene) to 11.4 (ethylbenzene) revertants m3 mgC-1 h-1. The mutagenicity was due exclusively to direct-acting late-generation products of the photooxidation reactions. Gas-phase chemical analysis showed that a number of oxidized organic chemical species enhanced during the irradiated exposure experiments correlated (r ≥ 0.81) with the mutagenic potencies of the atmospheres. Molecular formulas assigned to these species indicated that they likely contained peroxy acid, aldehyde, alcohol, and other functionalities.

  11. Assessment of Cellular Mutagenicity of Americano Coffees from Popular Coffee Chains.

    Science.gov (United States)

    Liu, Zhen-Shu; Chen, Po-Wen; Wang, Jung-Yu; Kuo, Tai-Chen

    2017-09-01

    Coffee is a popular beverage worldwide, but coffee beans can be contaminated with carcinogens. The Ames Salmonella mutagenicity test is often used for analysis of carcinogens for mutagenicity. However, previous studies have provided controversial data about the direct mutagenicity of coffee beans based on Ames test results. This study was conducted to determine the mutagenicity of popular Americano coffee based on results from the Ames test. Coffee samples without additives that were served by five international coffee chain restaurants were subjected to the analysis using Salmonella Typhimurium tester strains TA98, TA100, and TA1535. The levels of bacterial revertants in samples from coffee chains were lower than the twofold criterion of the control sets, and no significant dose-response effect was observed with or without rat liver enzyme activation. These data indicate that Americano coffees from the selected coffee chains possessed no direct mutagenic activity with or without enzyme activation. These findings suggest a low mutagenic risk from Americano coffees served by the selected coffee chains and support the use of other methods to confirm the nonmutagenicity of coffee products. These results are consistent with most recent epidemiological reports.

  12. Lack of mutagens in deep-fat-fried foods obtained at the retail level.

    Science.gov (United States)

    Taylor, S L; Berg, C M; Shoptaugh, N H; Scott, V N

    1982-04-01

    The basic methylene chloride extract from 20 of 30 samples of foods fried in deep fat failed to elicit any mutagenic response that could be detected in the Salmonella typhimurium/mammalian microsome assay. The basic extracts of the remaining ten samples (all three chicken samples studied, two of the four potato-chip samples, one of four corn-chip samples, the sample of onion rings, two of six doughnuts, and one of three samples of french-fried potato) showed evidence of weak mutagenic activity. In these samples, amounts of the basic extract equivalent to 28.5-57 g of the original food sample were required to produce revertants at levels of 2.6-4.8 times the background level. Only two of the acidic methylene chloride extracts from the 30 samples exhibited mutagenic activity greater than 2.5 times the background reversion level, and in both cases (one corn-chip and one shrimp sample) the mutagenic response was quite weak. The basic extract of hamburgers fried in deep fat in a home-style fryer possessed higher levels of mutagenic activity (13 times the background reversion level). However, the mutagenic activity of deep-fried hamburgers is some four times lower than that of pan-fried hamburgers.

  13. [EVALUATION OF THE CYTOGENETIC AND MUTAGEN-MODIFYING ACTIVITY OF CAFFEINE IN MOUSE BONE MARROW CELLS].

    Science.gov (United States)

    Durnev, A D; Kulakova, A V; Zhanataev, A K; Oganesiants, L A

    2015-01-01

    The cytogenetic and mutagen-modifying activity of caffeine was studied with the method of chromosomal aberrations in bone marrow cells of mice hybrids F1 CBAxC57BL/6. Caffeine per se was administered intragastrically or intraperitoneally, and in combination with mutagens--intragastrically. Mutagens injected intraperitoneally. Caffeine at doses of 10 and 100 mg/kg (single dose) and 10 mg/kg (five days) in parenteral administration and oral introduction failed to possess cytogenetic activity. In combination with mutagens caffeine (1, 10 and 100 mg/kg) had no effect on the cytogenetic activity of dioxydine (200 mg/kg/intraperitoneally) for a single coadministration, five-day pre or five-day coadministration. In combination with other mutagens under the same processing conditions caffeine at doses of 10 and 100 mg/kg significantly increased cytogenetic effects of cyclophosphamide (20 mg/kg) in the pretreatment of the animals and at the dose of 100 mg/kg significantly attenuated the cytogenetic effect of cisplatin (5 mg/kg) in single and repeated co-administration. Thus we have shown the absence of caffeine cytogenetic activity in vivo and showed the multidirectional effect of caffeine in doses far exceeding its daily consumption, to the manifestation ofcytogenetic effects of certain chemical mutagens in some modes of processing animals.

  14. Biologically important radiation damage in DNA

    International Nuclear Information System (INIS)

    Ward, J.F.

    1994-01-01

    Most DNA damage by the hydroxyl radical is confined to the bases, and this base damage represents an important component of locally multiply demanded sites (LMOS). The yields of the major damaged bases have been determined by gas chromatography mass spectrometry. For our propose, it was necessary to convert a known fraction of these damaged bases to strand breaks and then assay these labile sites as the increase in strand break yield over the normally observed level. Three potential agents by which this strategy of conversion of base damage to strand break could be implemented were identified in the original application: 1, Sl nuclease; 2, piperidine; and 3, base damage specific enzymes

  15. Dicholesteroyl diselenide: cytotoxicity, genotoxicity and mutagenicity in the yeast Saccharomyces cerevisiae and in Chinese hamster lung fibroblasts.

    Science.gov (United States)

    de Oliveira, Iuri Marques; Degrandi, Tiago Hoerbe; Jorge, Patrícia Mendes; Saffi, Jenifer; Rosa, Renato Moreira; Guecheva, Temenouga Nikolova; Henriques, João Antonio Pêgas

    2014-03-15

    The organoselenium compound, dicholesteroyl diselenide (DCDS) is a structural analogue of diphenyl diselenide (DPDS) and may be considered as a promising antioxidant drug in vivo. Nevertheless, little is known about the toxicological properties of DCDS. In the present study we evaluated the cytotoxic, genotoxic and mutagenic properties of DCDS in Chinese hamster lung fibroblasts (V79) and in strains of the yeast Saccharomyces cerevisiae, proficient and deficient in several DNA-repair pathways. The results with V79 cells show that DCDS induced cytotoxicity, GSH depletion and elevation of lipid peroxidation at lower concentrations than did DPDS. DCDS also generated single- and double-strand DNA breaks in V79 cells, both in the presence and in the absence of metabolic activation, as revealed by alkaline and neutral comet assays. Moreover, the induction of oxidative DNA base-damage was demonstrated by means of a modified comet assay with formamidopyrimidine-DNA glycosylase and endonuclease III. Treatment with DCDS also induced micronucleus formation in V79 cells as well as point and frame-shift mutations in a haploid wild-type strain of S. cerevisiae. Yeast mutants defective in base excision-repair proteins were the most sensitive to DCDS. Pre-incubation with N-acetylcysteine reduced DCDS's oxidative, genotoxic and mutagenic effects in yeast and in V79 cells. Our findings indicate that the presence of cholesteroyl substituents in DCDS results in elevation of its cytotoxic and genotoxic potential compared with that of DPDS in yeast and in V79 cells. However, due to dose-dependent contrasting behaviour of organoselenium compounds and differences in their toxicity in in vitro and in vivo systems, further studies are needed in order to establish the non-toxic concentration range for treatment in mammals. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. The mutation frequency of 8-oxo-7,8 dihydroguanine (8-oxoG) situated in a multiply damaged site: comparison of a single and two closely opposed 8-oxodG in Escherichia coli

    International Nuclear Information System (INIS)

    Malyarchuk, S.G.; Youngblood, R.C.; Landry, A.M.; Quillin, E.; Harrison, L.

    2003-01-01

    Full text: A multiply damaged site (MDS) is defined as >= two lesions within a distance of 10-15 base pairs (bp). MDS generated by ionizing radiation contains oxidative base damage, and in vitro studies have indicated that if the base damage is less than 3 bp apart, repair of one lesion is inhibited until repair of the lesion in the opposite strand is completed. Inhibition of repair could result in an increase in the mutation frequency of the base damage. We have designed an assay to determine whether a closely opposed lesion causes an increase in adenine insertion opposite an 8-oxodG in bacteria. The double-stranded oligonucleotides (with no damage, each single 8-oxodG or the MDS) were ligated into the firefly luciferase coding region of a reporter vector and transformed into wild type or MutY-deficient bacteria. The MDS contained an 8-oxodG in the transcribed strand (T) and a second 8-oxodG immediately 5' to this lesion in the non-transcribed strand (NT). During two rounds of replication, insertion of adenine opposite the 8-oxodG in the T or NT strand results in a translation termination codon at position 444 or 445, respectively. In wild-type bacteria, we detected a translation stop at a frequency of 0.15% (codon 444) and 0.09% (codon 445) with a single 8-oxodG in the T or NT strand, respectively. This was enhanced ∼3 fold when single lesions were replicated in MutY-deficient bacteria. Positioning an 8-oxodG in the T strand within the MDS enhanced the mutation frequency by ∼2 fold in wild-type bacteria and 8 fold in Mut Y-deficient bacteria, while the mutation frequency of the 8-oxodG in the NT strand increased by 6 fold in Mut Y-deficient bacteria. This enhancement of mutation frequency supports the in vitro MDS studies, which demonstrated the inability of base excision repair to completely repair closely opposed lesions

  17. Assessment of DNA Damage in Peripheral Blood Lymphocytes of Radiation Workers at Al-Tuwaitha Site by Using the Sister Chromatid Exchange and the Comet Assay

    International Nuclear Information System (INIS)

    Ali, A.K.; Muttar, A.J.; Khayon, S.K.; Haider, Y.L.; Ali, H.F.; Abdullah, A.K.

    2015-01-01

    The sister chromatid exchange was performed on peripheral blood lymphocytes obtained from 40 individuals of workers occupationally exposed to low ionizing radiation doses in Al-Tuwaitha site due to decommissioning to radioactive contamination then compared with 40 control individuals living in Baghdad. SCEs were scored in metaphase chromosomes were identified by fluorescent plus Giemsa staining (Figure 2).The mean frequencies of SCEs per cell differed significantly (p≺0 0.05) between individuals of radiation workers and control, being 7.78 0.45 SCE/cells and 6.28 0.22 SCE/cells , respectively. However SCE frequency was statistically significant (P≺0 0.05) among radiation workers as compared to control individuals.

  18. Use of molecular cytogenetic analysis as bio marker in assessment of DNA damage in radiation workers at Al-Twuathia site Iraq

    International Nuclear Information System (INIS)

    Abdulsahib, K. A.; Amel, J. M.; Abdullah, A.K.; Haider, Y.L.; Ali, H.F.; Khawla, A.B.

    2012-12-01

    The present study aims to use the biological techniques in a genotoxicity assessment of low doses of radiation in samples of workers in Al-Tuwatha site due to decommissioning to radioactive contamination as a result of work. Used three molecular genetic techniques as included micronuclei in cytoplasm of reticulocytes cells, buccal micronuclei cymate assay and alkaline comet assay. this study including 50 blood samples, aged (35 - 63) as well as 50 blood samples which are not smokers and alcohol as control group which including (35 and 15) aged (25 - 57 year) for the test of micronuclei in cytoplasm of reticulocytes. While the comet assay and buccal micronuclei cymate assay which including blood and cheek swab samples from 25 aged (30 - 56), as well as 25 blood and cheek swab samples which are not smokers and alcohol as control group which including (15 and 10) aged (25 - 57 year). The frequencies of micronuclei in cytoplasm of reticulocytes observed for the radiation workers at Tl-Tuwaith site were significantly (P<0.05) higher than in the control group. Similarly, the comet parameter were statistically higher (P<0.05) in the radiation workers group in comparison with the control group. Also, the results obtained showed statistically significant differences (P-<0.05 between comet tail length and tail moment values measured in radiation worker and control groups. In the case of buccal micronuclei assay, no significant (P<0.05) differences between both group was found. In conclusion, the results indicated that there is a possibility of using the changes in the levels of micronuclei in cytoplasm of reticulocytes, and comet assay useful as results obtained confirmed usefulness of the alkaline comet assay as a sensitive additional bio marker in the regular health screening of workers occupationally exposed to low doses of ionizing radiation.(Author)

  19. Antigenotoxic activity of lactic acid bacteria, prebiotics, and products of their fermentation against selected mutagens.

    Science.gov (United States)

    Nowak, Adriana; Śliżewska, Katarzyna; Otlewska, Anna

    2015-12-01

    Dietary components such as lactic acid bacteria (LAB) and prebiotics can modulate the intestinal microbiota and are thought to be involved in the reduction of colorectal cancer risk. The presented study measured, using the comet assay, the antigenotoxic activity of both probiotic and non-probiotic LAB, as well as some prebiotics and the end-products of their fermentation, against fecal water (FW). The production of short chain fatty acids by the bacteria was quantified using HPLC. Seven out of the ten tested viable strains significantly decreased DNA damage induced by FW. The most effective of them were Lactobacillus mucosae 0988 and Bifidobacterium animalis ssp. lactis Bb-12, leading to a 76% and 80% decrease in genotoxicity, respectively. The end-products of fermentation of seven prebiotics by Lactobacillus casei DN 114-001 exhibited the strongest antigenotoxic activity against FW, with fermented inulin reducing genotoxicity by 75%. Among the tested bacteria, this strain produced the highest amounts of butyrate in the process of prebiotic fermentation, and especially from resistant dextrin (4.09 μM/mL). Fermented resistant dextrin improved DNA repair by 78% in cells pre-treated with 6.8 μM methylnitronitrosoguanidine (MNNG). Fermented inulin induced stronger DNA repair in cells pre-treated with mutagens (FW, 25 μM hydrogen peroxide, or MNNG) than non-fermented inulin, and the efficiency of DNA repair after 120 min of incubation decreased by 71%, 50% and 70%, respectively. The different degrees of genotoxicity inhibition observed for the various combinations of bacteria and prebiotics suggest that this effect may be attributable to carbohydrate type, SCFA yield, and the ratio of the end-products of prebiotic fermentation. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Induction of male sterility in rice using chemical mutagens

    Energy Technology Data Exchange (ETDEWEB)

    Minocha, J L; Gupta, R K [Department of Genetics, Punjab Agricultural University, Ludhiana (India)

    1988-07-01

    Full text: To diversify the sources of cytoplasmic male sterility for hybrid seed production in rice (Oryza sativa L.) attempts were made to induce this character in a popular indica cultivar PR 106 through chemical mutagens. Seeds were treated with 0.4% ethidium bromide (EB) for 24 or 48h at 10 deg. C, with 0.4% ethyl methanesulphonate (EMS) for 24 or 48h at 10 deg. C for 16 hr at 20 deg. C or with 0.2% streptomycin sulphate (SM) for 24 or 48 hr at 10 deg. C. In M{sub 2} male sterile plants were detected in eleven different progenies, one from SM treatment and the remaining from EMS treatments. All the sterile plants had 100% non-stainable aborted pollen. Seed set upon open-pollination of the male sterile plants with the variety PR 106 ranged from 0.03 to 4.93 per cent whereas no seed formed in bagged panicles. In M{sub 3}, open-pollinated progenies of the male sterile plants and their fertile sibs were further studied. Two progenies segregated for male sterility, all others had only fertile plants. In one of the segregating progenies, five out of six and in the other nine out of fourteen plants were male sterile. The progenies of fertile sibs did not have any male sterile plant. The results indicate that sterility of cytoplasmic type has been induced by EMS. The parental variety PR 106 acts as the maintainer. (author)

  1. Is ultraviolet enhanced reactivation of mammalian virus mutagenic

    International Nuclear Information System (INIS)

    Bockstahler, L.E.; Hellman, K.B.; Cantwell, J.M.; Strickland, A.

    1981-01-01

    Ultraviolet enhanced reactivation consists of an increase in the survival of certain uv-irradiated mammalian viruses when assayed for infectivity in uv-irradiated host mammalian cells, as compared with unirradiated cells. In this report ultraviolet enhanced reactivation is described, and a review is presented of investigations from this and other laboratories to establish whether or not this process is mutagenic. The answer to this question may help establish if error-prone DNA repair is induced in irradiated mammalian cells. We approached the mutagenesis question by examining the phenotypic reversion of a uv-irradiated temperature sensitive mutant of Herpes simplex virus to wild type growth in uv-irradiated monkey kidney cells. Apparent reversion was observed in both irradiated and unirradiated cells. No correlation could be found between the extent of reversion and uv exposure to the cells. The conclusions from studies reported by other investigators using various mammalian virus mutagenesis systems are conflicting. It was generally agreed that viral mutagenesis occurs when irradiated virus is passaged through either irradiated or unexposed cells. However, in some studies it was found that the frequency of mutagenesis in irradiated cells was greater than that in unirradiated cells, while in other studies increased mutagenesis in irradiated cells was not observed

  2. Mutagenic DNA repair in Escherichia coli: Pt. 17

    International Nuclear Information System (INIS)

    Sharif, F.; Bridges, B.A.

    1990-01-01

    In contrast to the dnaE485 mutation, which is nearly 'dead-stop', dnaE1026 allows DNA synthesis for some time at restrictive temperatures. When bacteria carrying the dnaE486 or dnaE1026 temperature-sensitive mutations were incubated at restrictive temperature after exposure to UV light they showed little or no fixation of mutations as determined by loss of photoreversibility and the mutation frequency fell progressively. These results confirm a role for DnaE protein in UV mutagenesis. A derivative of dnaE1026 carrying the umuC122 allele which blocks normal UV mutagenesis showed induction of mutations when photoreversing light was given to UV-irradiated bacteria after a period of incubation at either permissive or restrictive temperature. The defective DnaE1026 protein is therefore able to carry out the misincorporations postulated to be the first step in the mutagenic process. Its inability to give rise to mutations in umu + bacteria may therefore be attributed to its inability to participate in a later step. In contrast, UV-irradiated dnaE486 umuC122 bacteria did not show mutagenesis when incubated at restrictive temperature before photoreversal, suggesting that the altered DnaE486 protein was not able to carry out the postulate misincorporation step at 43 0 C. DNA polymerase III α-subunit therefore appears to be required for both the misincorporation and bypass steps in the two-step model for UV mutagenesis. (Author)

  3. Mutagenic effects of nitrogen and carbon ions on stevia

    International Nuclear Information System (INIS)

    Wang Cailian; Chen Qiufang; Shen Mei; Lu Ting; Shu Shizhen

    1998-06-01

    Dry seeds of stevia were implanted by 60∼100 keV nitrogen ion and 75 keV carbon ion with various doses. The biological effects in M 1 and mutation in M 2 were studied. The results showed that ion beam was able to induce variation on chromosome structure and inhibited mitosis action in root tip cells. The rate of cells with chromosome aberration was increased with the increase of ion beam energy and dose. Energy effects of mitosis were presented between 75 keV and 60, 100 keV. As compared with γ-rays, the effects of ion beam were lower on chromosomal aberration but were higher on frequency of the mutation. The rate of cell with chromosome aberration and M 2 useful mutation induced by implantation of carbon ion was higher than those induced by implantation of nitrogen ion. Mutagenic effects of Feng 1 x Ri Yuan and of Ri Yuan x Feng 2 are higher than that of Ji Ning and Feng 2

  4. Induction of male sterility in rice using chemical mutagens

    International Nuclear Information System (INIS)

    Minocha, J.L.; Gupta, R.K.

    1988-01-01

    Full text: To diversify the sources of cytoplasmic male sterility for hybrid seed production in rice (Oryza sativa L.) attempts were made to induce this character in a popular indica cultivar PR 106 through chemical mutagens. Seeds were treated with 0.4% ethidium bromide (EB) for 24 or 48h at 10 deg. C, with 0.4% ethyl methanesulphonate (EMS) for 24 or 48h at 10 deg. C for 16 hr at 20 deg. C or with 0.2% streptomycin sulphate (SM) for 24 or 48 hr at 10 deg. C. In M 2 male sterile plants were detected in eleven different progenies, one from SM treatment and the remaining from EMS treatments. All the sterile plants had 100% non-stainable aborted pollen. Seed set upon open-pollination of the male sterile plants with the variety PR 106 ranged from 0.03 to 4.93 per cent whereas no seed formed in bagged panicles. In M 3 , open-pollinated progenies of the male sterile plants and their fertile sibs were further studied. Two progenies segregated for male sterility, all others had only fertile plants. In one of the segregating progenies, five out of six and in the other nine out of fourteen plants were male sterile. The progenies of fertile sibs did not have any male sterile plant. The results indicate that sterility of cytoplasmic type has been induced by EMS. The parental variety PR 106 acts as the maintainer. (author)

  5. Measurement of oxidative damage to DNA in nanomaterial exposed cells and animals

    DEFF Research Database (Denmark)

    Møller, Peter; Jensen, Ditte Marie; Christophersen, Daniel Vest

    2015-01-01

    -reactivity with other molecules in cells. This review provides an overview of efforts to reliably detect oxidatively damaged DNA and a critical assessment of the published studies on DNA damage levels. Animal studies with high baseline levels of oxidatively damaged DNA are more likely to show positive associations...... of oxidatively damaged DNA in lung tissue. Oral exposure to nanosized carbon black, TiO2 , carbon nanotubes and ZnO is associated with elevated levels of oxidatively damaged DNA in tissues. These observations are supported by cell culture studies showing concentration-dependent associations between ENM exposure...... and oxidatively damaged DNA measured by the comet assay. Cell culture studies show relatively high variation in the ability of ENMs to oxidatively damage DNA; hence, it is currently impossible to group ENMs according to their DNA damaging potential. Environ. Mol. Mutagen., 2014. © 2014 Wiley Periodicals, Inc....

  6. Analysis of mutagenic DNA repair in a thermoconditional mutant of Saccharomyces cerevisiae. IV. Influence of DNA replication and excision repair on REV2 dependent UV-mutagenesis and repair

    Energy Technology Data Exchange (ETDEWEB)

    Siede, W.; Eckardt, F.

    1986-01-01

    A double mutant being thermoconditionally defective in mutation induction as well as in repair of pre-lethal UV-induced DNA damage (rev2ts) and deficient in excision repair (rad3-2) was studied in temperature-shift experiments. The influence of inhibitors of DNA replication (hydroxyurea, aphidicolin) was determined. Additionally, an analysis of the dose-response pattern of mutation induction (mutation kinetics) at several ochre alleles was carried out. It was concluded that the UV-inducible REV2 dependent mutagenic repair process is not induced in excision-deficient cells. In excision-deficient cells, REV2 dependent mutation fixation is slow and mostly post-replicative though not dependent on DNA replication. The REV2 mediated mutagenic process could be separated from the repair function.

  7. mei-9/sup a/ mutant of Drosophila melanogaster increases mutagen sensitivity and decreases excision repair

    International Nuclear Information System (INIS)

    Boyd, J.B.; Golino, M.D.; Setlow, R.B.

    1976-01-01

    The mei-9/sup a/ mutant of Drosophila melanogaster, which reduces meiotic recombination in females, is deficient in the excision of uv-induced pyrimidine dimers in both sexes. Assays were performed in primary cultures and established cell lines derived from embryos. An endonuclease preparation from M. luteus, which is specific for pyrimidine dimers, was employed to monitor uv-induced dimers in cellular DNA. The rate of disappearance of endonuclease-sensitive sites from DNA of control cells is 10-20 times faster than that from mei-9/sup a/ cells. The mutant mei-218, which is also deficient in meiotic recombination, removes nuclease-sensitive sites at control rates. The mei-9/sup a/ cells exhibit control levels of photorepair, postreplication repair and repair of single strand breaks. In mei-9 cells DNA synthesis and possibly postreplication repair are weakly sensitive to caffeine. Larvae which are hemizygous for either of the two mutants that define the mei-9 locus are hypersensitive to killing by the mutagens methyl methanesulfonate, nitrogen mustard and 2-acetylaminofluorene. Larvae hemizygous for the mei-218 mutant are insensitive to each of these reagents. These data demonstrate that the mei-9 locus is active in DNA repair of somatic cells. Thus functions involved in meiotic recombination are also active in DNA repair in this higher eukaryote. The results are consistent with the earlier suggestions that the mei-9 locus functions in the exchange events of meiosis. The mei-218 mutation behaves differently in genetic tests and our data suggest its function may be restricted to meiosis. These studies demonstrate that currently recognized modes of DNA repair can be efficiently detected in primary cell cultures derived from Drosophila embryos

  8. Estimated airborne release of radionuclides from the Battelle Memorial Institute Columbus Laboratories JN-1b building at the West Jefferson site as a result of postulated damage from severe wind and earthquake hazard

    International Nuclear Information System (INIS)

    Mishima, J.; Ayer, J.E.

    1981-11-01

    The potential airborne releases of radionuclides (source terms) that could result from wind and earthquake dmage are estimated for the Battelle Memorial Institute Columbus Laboratories JN-1b Building at the West Jefferson site in Ohio. The estimated source terms are based on the damage to barriers containing the radionuclides, the inventory of radionuclides at risk, and the fraction of the inventory made airborne as a result of the loss of containment. In an attempt to provide a realistic range of potential source terms that include most of the normal operating conditions, a best estimate bounded by upper and lower limits is calculated by combining the upper-bound, best-estimate, and lower-bound inventories-at-risk with an airborne release factor (upper-bound, best-estimate, and lower-bound if possible) for the situation. The factors used to evaluate the fractional airborne release of materials and the exchange rates between enclosed and exterior atmospheres are discussed. The postulated damage and source terms are discussed for wind and earthquake hazard scenarios in order of their increasing severity

  9. Mutagenicity of ultraviolet A radiation in the lacI transgene in Big Blue mouse embryonic fibroblasts

    International Nuclear Information System (INIS)

    Kim, Sang-in; Pfeifer, Gerd P.; Besaratinia, Ahmad

    2007-01-01

    Sunlight ultraviolet A (UVA) irradiation has been implicated in the etiology of human skin cancer. A genotoxic mode of action for UVA radiation has been suggested that involves photosensitization reactions giving rise to promutagenic DNA lesions. We investigated the mutagenicity of UVA in the lacI transgene in Big Blue mouse embryonic fibroblasts. UVA irradiation of these cells at a physiologically relevant dose of 18 J/cm 2 caused a 2.8-fold increase in the lacI mutant frequency relative to control, i.e., 12.12 ± 1.84 versus 4.39 ± 1.99 x 10 -5 (mean ± S.D.). DNA sequencing analysis showed that of 100 UVA-induced mutant plaques and 54 spontaneously arisen control plaques, 97 and 51, respectively, contained a minimum of one mutation along the lacI transgene. The vast majority of both induced- and spontaneous mutations were single base substitutions, although less frequently, there were also single and multiple base deletions and insertions, and tandem base substitutions. Detailed mutation spectrometry analysis revealed that G:C → T:A transversions, the signature mutations of oxidative DNA damage, were significantly induced by UVA irradiation (P -5 ; P < 0.00001). These findings are in complete agreement with those previously observed in the cII transgene of the same model system, and reaffirm the notion that intracellular photosensitization reactions causing promutagenic oxidative DNA damage are involved in UVA genotoxicity

  10. Organic mutagens and drinking water in The Netherlands : a study on mutagenicity of organic constituents in drinking water in The Netherlands and their possible carcinogenic effects

    NARCIS (Netherlands)

    Kool, H.J.

    1983-01-01

    Several mutagenic and carcinogenic organic compounds have been detected in Dutch surface waters and in drinking water prepared from these surface waters. Although the levels of these compounds in drinking- and surface water are relatively low, in general below μg per litre, it appeared that organic

  11. Radiation damage

    CERN Document Server

    Heijne, Erik H M; CERN. Geneva

    1998-01-01

    a) Radiation damage in organic materials. This series of lectures will give an overview of radiation effects on materials and components frequently used in accelerator engineering and experiments. Basic degradation phenomena will be presented for organic materials with comprehensive damage threshold doses for commonly used rubbers, thermoplastics, thermosets and composite materials. Some indications will be given for glass, scintillators and optical fibres. b) Radiation effects in semiconductor materials and devices. The major part of the time will be devoted to treat radiation effects in semiconductor sensors and the associated electronics, in particular displacement damage, interface and single event phenomena. Evaluation methods and practical aspects will be shown. Strategies will be developed for the survival of the materials under the expected environmental conditions of the LHC machine and detectors. I will describe profound revolution in our understanding of black holes and their relation to quantum me...

  12. Using Saccharomyces cerevisiae to Test the Mutagenicity of Household Compounds: An Open Ended Hypothesis-Driven Teaching Lab

    OpenAIRE

    Marshall, Pamela A.

    2007-01-01

    In our Fundamentals of Genetics lab, students perform a wide variety of labs to reinforce and extend the topics covered in lecture. I developed an active-learning lab to augment the lecture topic of mutagenesis. In this lab exercise, students determine if a compound they bring from home is a mutagen. Students are required to read extensive background material, perform research to find a potential mutagen to test, develop a hypothesis, and bring to the lab their own suspected mutagen. This lab...

  13. Quantitative mammalian cell mutagenesis and mutagen screening: study with CHO cells

    International Nuclear Information System (INIS)

    Hsie, A.W.; O'Neill, J.P.; San Sebastian, J.R.; Brimer, P.A.

    1979-01-01

    The CHO/HGPRT system has been developed and defined for quantifying mutation induced by various physical and chemical agents at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in Chinese hamster ovary (CHO) cells. In all direct-acting chemical mutagens studied, mutation induction increases linearly as a function of the concentration, with no apparent threshold. Some chemicals induce mutation at non-cytotoxic concentrations. The mutagenicity of ethyl methanesulfonate has been quantified as a function of exposure concentration x treatment time. The sensitive and quantitative nature of the system enables studies of the structure-activity (mutagenicity) relationships of various classes of chemicals, including alkylating agents, heterocyclic nitrogen mustards, and platinum compounds. When rat liver S 9 -mediated metabolic activation is present, procarcinogens such as benzo(a)pyrene, 2-acetylaminofluorene, and dimethylnitrosamine are mutagenic, whereas their noncarcinogenic structural analogues pyrene, fluorene, and dimethylamine are not. The system has been shown to be useful in determining the interactive effects between physical and chemical agents, and in screening for mutagenicity of fractionated organic mixtures and industrial chemicals in both liquid and gaseous state. For the system to be used successfully in routine screening, further studies should be directed toward the development of a metabolic activation system suitable for a broad spectrum of chemicals, a sensitive and reliable statistical method, and an experimental design to determine compounds with low mutagenicity. The system has been expanded for determination of mutagen-induced chromosome aberration, sister-chromatid exchange, and micronucleus formation in addition to gene mutation and cytotoxicity; it can also be used to study inhibition of DNA synthesis

  14. Inhibition of mutagenicity of N-methyl-N-nitrosourea by ellagic acid

    International Nuclear Information System (INIS)

    Dixit, R.; Gold, B.

    1986-01-01

    Ellagic acid (EA), a plant phenol present in a variety of soft fruits and vegetables, has been shown to possess antimutagenic and anticarcinogenic properties against bay region diol epoxide of polycyclic aromatic hydrocarbons. It is suggested that EA forms an adduct with diol epoxide of benzo (α) pyrene and thus prevents its binding to DNA. To better understand the mechanism of reactivity and inhibition properties of EA, we studied the effect of EA on mutagenicity and DNA alkylation of carcinogenic N-nitroso compounds, including N-methyl-N-nitrosourea (MNU) and N-methyl-N'-nitro-Nnitrosoguanidine (MNNG). MNU and MNNG are direct-acting mutagens requiring no metabolic activation. MNU showed a linear dose response between the concentration range of 50 to 400 nmole in an Ames/Salmonella mammalian mutagenicity test. EA at concentrations of 100, 250, 500, and 1,000 nmole inhibited the mutagenicity of MNU (400 nmole) by 3, 13, 45,and 60%, respectively. MNNG produced a nonlinear dose response in mutagenicity between the concentrations of 0.5 to 4 nmole. EA showed no appreciable inhibition of MNNG mutagenicity. Inhibition of DNA alkylation by MNU and MNNG by EA was studied by preincubating 50 to 200 nmole of EA with 200 nmole of ( 3 H)-MNU or ( 3 H)-MNNG for 10 min at 37 0 c, followed by incubation of polymer deoxyguanosine: deoxycytosine (poly dG:dC) (1 unit) overnight. EA caused no inhibitory effect on MNNG alkylation of poly dG:dC. Experiments on the effect of EA on alkylation of DNA and formation of nucleoside adducts by MNU are in progress, and results will be discussed with reference to MNU and MNNG mutagenicity and EA inhibition

  15. Single thrombopoietin dose alleviates hematopoietic stem cells intrinsic short- and long-term ionizing radiation damage. In vivo identification of anatomical cell expansion sites.

    Science.gov (United States)

    Tronik-Le Roux, Diana; Nicola, Marie-Anne; Vaigot, Pierre; Nurden, Paquita

    2015-01-01

    Hematopoietic stem cells (HSC) are essential for maintaining the integrity of complex and long-lived organisms. HSC, which are self-renewing, reconstitute the hematopoietic system through out life and facilitate long-term repopulation of myeloablated recipients. We have previously demonstrated that when mice are exposed to sublethal doses of ionizing radiation, subsets of the stem/progenitor compartment are affected. In this study we examine the role of thrombopoietin (TPO) on the regenerative capacities of HSC after irradiation and report the first demonstration of efficacy of a single injection of TPO shortly after in vivo exposure to ionizing radiation for reducing HSC injury and improving their functional outcome. Our results demonstrate that TPO treatment not only reduced the number of apoptotic cells but also induced a significant modification of their intrinsic characteristics. These findings were supported by transplantation assays with long-term HSC that were irradiated or unirradiated, TPO treated or untreated, in CD45.1/CD45.2 systems and by using luciferase-labeled HSC for direct bioluminescence imaging in living animals. Of particular importance, our data demonstrate the skull to be a highly favorable site for the TPO-induced emergence of hematopoietic cells after irradiation, suggesting a TPO-mediated relationship of primitive hematopoietic cells to an anatomical component. Together, the data presented here: provide novel findings about aspects of TPO action on stem cells, open new areas of investigation for therapeutic options in patients who are treated with radiation therapy, and show that early administration of a clinically suitable TPO-agonist counteracts the previously observed adverse effects.

  16. Tort Damages

    NARCIS (Netherlands)

    L.T. Visscher (Louis)

    2008-01-01

    textabstractAbstract: In this Chapter, I provide an overview of Law and Economics literature regarding tort damages. Where necessary, attention is also spent to rules of tort liability. Both types of rules provide behavioral incentives to both injurers and victims, with respect to their level of

  17. Quantification of the genetic risk of environmental mutagens

    International Nuclear Information System (INIS)

    Ehling, U.H.

    1988-01-01

    Screening methods are used for hazard identification. Assays for heritable mutations in mammals are used for the confirmation of short-term test results and for the quantification of the genetic risk. There are two main approaches in making genetic risk estimates. One of these, termed the direct method, expresses risk in terms of the expected frequency of genetic changes induced per unit. The other, referred to as the doubling dose method or the indirect method, expresses risk in relation to the observed incidence of genetic disorders now present in man. The indirect method uses experimental data only for the calculation of the doubling dose. The quality of the risk estimation depends on the assumption of persistence of the induced mutations and the ability to determine the current incidence of genetic diseases. The difficulties of improving the estimates of current incidences of genetic diseases or the persistence of the genes in the population led them to the development of an alternative method, the direct estimation of the genetic risk. The direct estimation uses experimental data for the induced frequency for dominant mutations in mice. For the verification of these quantifications one can use the data of Hiroshima and Nagasaki. According to the estimation with the direct method, one would expect less than 1 radiation-induced dominant cataract in 19,000 children with one or both parents exposed. The expected overall frequency of dominant mutations in the first generation would be 20-25, based on radiation-induced dominant cataract mutations. It is estimated that 10 times more recessive than dominant mutations are induced. The same approaches can be used to determine the impact of chemical mutagens

  18. Ames Mutagenicity Assessment of Flavored Water Pipe Tobacco Products :A Cross Sectional Study in Tehran

    Directory of Open Access Journals (Sweden)

    Shahrzad Sadri

    2016-12-01

    Full Text Available Waterpipe smoking has become a global youth trend especially in the Middle East countries and Iran . The aim of this study was to determine the mutagenic effects of three most popular flavored tobaccos by four different salmonella typhimurium strains and compare the possible mutagenic effects of the test samples. Ames mutagenicity assessment was conducted according to the OECD guideline using TA100, TA98 , YG1024 and YG1029 strains. Charcoal burned flavored tobaccos of three different flavors including Orange, Double Apple, and Lime Mint were filtered and exposed to all strains after strain identification tests and MIC ,MBC determinations. The Ames test results indicated significant mutagenic effects of tobacco samples in all four test strains when compared with negative control (p≤0.0001. The highest Mutagenic Factor (MF was seen in Double Apple samples using TA 98 (MF=11.5±3.3 . In all experiments, TA strains showed higher sensitivity to the samples than YG strains which suggest these two strains for further regulatory toxicity tests ,policy making purposes and tobacco control programs . Present results represents an important step in understanding the genotoxic potentials of three most popular flavored tobaccos samples of a famous brand in the global markets .

  19. Mutagenicity of food-derived carcinogens and the effect of antioxidant vitamins.

    Science.gov (United States)

    Montgomery, Beverly A; Murphy, Jessica; Chen, James J; Desai, Varsha G; McGarrity, Lynda; Morris, Suzanne M; Casciano, Daniel A; Aidoo, Anane

    2002-01-01

    The food-derived heterocyclic amines (HCAs) 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are mutagenic in the Ames test and produce tumors in laboratory animals, including monkeys. These HCAs have also been shown to induce gene mutations in vivo. To assess the antimutagenic effects of dietary antioxidant vitamins, beta-carotene, ascorbic acid (vitamin C), and alpha-tocopherol (vitamin E), on food-borne mutagenes/carcinogens, we evaluated the mutagenic activity of the compounds alone or combined with antioxidant vitamins. We utilized the rat lymphocyte mutation assay at the hypoxanthine guanine phosphoribosyl transferase (Hprt) locus. Female Fischer 344 rats treated with different doses (0, 2.5, 5.0, 25.0, and 50.0 mg/kg) of the carcinogens were sacrificed 5 wk after mutagen treatment. Although IQ and MeIQ slightly increased mutation frequency (MF) at some doses, a significant (P carcinogen metabolism would be affected by ingestion of vitamins. The activities of endogenous detoxification enzymes, glutathione S-transferase and glutathione peroxidase (GPx), were thus examined. Intake of beta-carotene and vitamin C without the carcinogen resulted in an increase (P food or taken as supplements could, in part, counteract such mutagenic activities.

  20. Quantitative measures of mutagenicity and multability based on mutant yield data

    International Nuclear Information System (INIS)

    Eckhardt, F.; Haynes, R.H.

    1980-01-01

    We describe, how mutant yield data (mutants per cell treated) can be used both to compare the mutagenenicity of different mutagens, and to characterize the mutability of different cell types. Yield curves reveal the net effect of the lethal and genetic actions of mutagens on cells. Normally, yields are the quantities measured in assays for mutagenesis, and rectilinear plots of such data baldly reveal the amount of experimental error and the extent of actual mutant induction above the background level. Plots of yield versus lethal hits can be used to quantify the relative mutagenenic efficiency (RME) of agents whose physical exposure doses otherwise would be incommensurable, as well as the relative mutability (Rmt) of different strains to the same mutagen. Plots of yield versus log dose provide an unambiguous way of assessing the relative mutational sensitivities (Rms) and mutational resolutions (Rmr) of different strains against a given mutagen. Such analysis is important for evaluation of the relative merits of excision-proficient and excision-deficient strains of the same organism as mutagen-testing systems. The mathematical approach outlined here is applied, by way of example, to measurements of UV and 4-NQO induced mutagenesis in both repair-deficient and repair-proficient haploid strains of the yeast Sacccharomyces cerevsiae. (orig.)

  1. Wholesomeness studies on gamma-irradiated smoked fish using short-term mutagenicity assays

    International Nuclear Information System (INIS)

    De la Rosa, A.M.; Banzon, R.B.

    1985-12-01

    The effect of gamma irradiation on the mutagenicity potential of wood-smoked mackerel (Rastrelliger sp.) was investigated. Smoked fish were irradiated with dose of 2.0, 4.0, 6.0 and 8.0 KGy, and tested for mutagenic activity using the Salmonella plate incorporation assay, host-mediated assay, and micronucleus test. The DMSO extract of unirradiated smoked fish was found to be mutagenic, without metabolic activation in Salmonella strains TA 100 and TA 104, both sensitive to base-pair substitution mutations. Strains TA 98 and TA 97 which are sensitive to frameshift mutations showed no mutagenic activity towards the same DMSO extract. The observed response towards the Salmonella strains was not affected by irradiation in the range of radiation doses studied. The presence of protamutagens in the DMSO extract of unirradiated smoked fish was not detected using the host-mediated assay. In another in-vivo test however, the same DMSO extract induced the formation of micronuclei in the bonemarrow cells of mice. Gamma irradiation up to a dose of 8.0 KGy did not affect the observed mutagenicity of wood-smoked fish. (author)

  2. Mutagenicity of smoke condensates from Canadian cigarettes with different design features.

    Science.gov (United States)

    Mladjenovic, Nemanja; Maertens, Rebecca M; White, Paul A; Soo, Evelyn C

    2014-01-01

    There is currently limited knowledge regarding the impact of different cigarette designs on the toxicological properties of cigarette smoke condensate (CSC). This study used the Salmonella Mutagenicity Assay to examine the mutagenic activity of mainstream CSCs from 11 commercial Canadian cigarette brands with different design features or tobacco blend. The brands were selected to include design features that are common for cigarettes sold in the Canadian market, as well as cigarettes with alternate filters (charcoal or MicroBlue™), the super slim design, and cigarettes containing mixed blends of different tobacco types. CSCs were obtained using the International Organization for Standardization (ISO) and Health Canada Intense (HCI) smoking regimes, and mutagenic activity was assessed using Salmonella strains TA98, YG1041 and YG5185. Comparisons of the commercial brands to the Kentucky 3R4F, the Canadian Monitor 8 reference and a Canadian best seller revealed no significant reduction in CSC mutagenicity for cigarettes with alternate filters. However, the super slim design did afford some reduction in mutagenic potency. Nevertheless, since the study did not attempt to evaluate the impact of the cigarette designs on human health at the individual or population level, the super slim cigarettes cannot be considered 'reduced-harm' cigarettes.

  3. Mutagenic activity of N-nitrosoethylene urea in higher plants. [C. cappilaris L

    Energy Technology Data Exchange (ETDEWEB)

    Sal' nikova, T.V.; Grigorova, N.V.; Laputin, D.L.; Shustova, L.L., Zazimko, V.V.; Shustov, G.V.; Kostyanovskiy, R.G.

    1984-04-01

    Cytopathogenetic effect of N-nitrosoethylene urea (NETM) on common wheat and C. cappilaris L. are studied. Air-dried wheat seeds were treated with 1 of 5 concentrations (0.1-0.01%) of NETM for 18 hours at pH 5.7 or 7.0. Treatment of seeds with NETM reduced the germinating power significantly at pH 5.7, especially at high concentrations of NETM. NETM is also a highly effective chemical mutagen. Maximum mutagenic effect appears at pH 7.0. NETM greatly reduced mitotic activity of wheat and C. cappilaris L. which is typical for alkylating type mutagens. The aberration rate is rather high for both objects studied. In both the anaphase and metaphase method of calculating chromosomal injuries, a great percentage of the total number of aberrations are chromatid type reconstructions which indicates predominance of the alkylating action of NETM. Wheat affected by NETM has a large number of anaphase cells with lagging chromosome which is atypical for alkylating type mutagens. This may be explained by the effect of NETM on centromeric and precentromeric parts of chromosomes and spindle filaments. NETM is an alkylating agent rather than a carbamoylating agent. It is a highly active and slightly toxic mutagen. 25 references, 1 figure.

  4. Assessment of diphenylcyclopropenone for photochemically induced mutagenicity in the Ames assay

    Energy Technology Data Exchange (ETDEWEB)

    Wilkerson, M.G.; Connor, T.H.; Henkin, J.; Wilkin, J.K.; Matney, T.S.

    1987-10-01

    The photochemical conversion of diphenylcyclopropenone to diphenylacetylene has recently been reported. Diphenylcyclopropenone is used in the treatment of alopecia areata and is nonmutagenic in a limited Ames assay. We examined diphenylcyclopropenone and diphenylacetylene, as well as synthetic precursors of diphenylcyclopropenone--dibenzylketone and alpha,alpha'-dibromodibenzylketone--for mutagenicity against TA100, TA98, TA102, UTH8413, and UTH8414. All compounds were nonmutagenic except alpha,alpha'-dibromodibenzylketone, which was a potent mutagen in TA100 with and without S-9 activation. The effect of photochemical activation of diphenylcyclopropenone in the presence of bacteria demonstrated mutagenicity in UTH8413 (two times background) at 10 micrograms/plate with S-9 microsomal activation. 8-Methoxypsoralen produces a mutagenic response in TA102 at 0.1 microgram/plate with 60 seconds of exposure to 350 nm light. In vitro photochemically activated Ames assay with S-9 microsomal fraction may enhance the trapping of short-lived photochemically produced high-energy mutagenic intermediates. This technique offers exciting opportunities to trap high-energy intermediates that may play an important role in mutagenesis. This method can be applied to a variety of topically applied dermatologic agents, potentially subjected to photochemical changes in normal use.

  5. Replication of UV-irradiated DNA in human cell extracts: Evidence for mutagenic bypass of pyrimidine dimers

    International Nuclear Information System (INIS)

    Thomas, D.C.; Kunkel, T.A.

    1993-01-01

    The authors have examined the efficiency and fidelity of simian virus 40-origin-dependent replication of UV-irradiated double-stranded DNA in extracts of human cells. Using as a mutational target the α-complementation domain of the Escherichia coli lacZ gene in bacteriophage M13mp2DNA, replication of undamaged DNA in HeLa cell extracts was highly accurate, whereas replication of DNA irradiated with UV light (280-320 nm) was both less efficient and less accurate. Replication was inhibited by irradiation in a dose-dependent manner. Nonetheless, covalently closed, monomer-length circular products were generated that were resistant to digestion by Dpn I, showing that they resulted from semiconservative replication. These products were incised by T4 endonuclease V, whereas the undamaged replication products were not, suggesting that pyrimidine dimers were bypassed during replication. When replicated, UV-irradiated DNA was used to transfect an E. coli α-complementation host strain to score mutant M13mp2 plaques, the mutant plaque frequency was substantially higher than that obtained with either unirradiated, replicated DNA, or unreplicated, UV-irradiated DNA. Both the increased mutagenicity and the inhibition of replication associated with UV irradiation were reversed by treatment of the irradiated DNA with photolyase before replication. Sequence analysis of mutants resulting from replication of UV-irradiated DNA demonstrated that most mutants contained C → T transition errors at dipyrimidine sites. A few mutants contained 1-nt frameshift errors or tandem double CC → TT substitutions. The data are consistent with the interpretation that pyrimidine dimers are bypassed during replication by the multiprotein replication apparatus in human cell extracts and that this bypass is mutagenic primarily via misincorporation of dAMP opposite a cytosine (or uracil) in the dimer. 56 refs., 2 figs., 3 tabs

  6. Trans-generational radiation-induced chromosomal instability in the female enhances the action of chemical mutagens

    International Nuclear Information System (INIS)

    Camats, Nuria; Garcia, Francisca; Parrilla, Juan Jose; Calaf, Joaquim; Martin, Miguel; Caldes, Montserrat Garcia

    2008-01-01

    Genomic instability can be produced by ionising radiation, so-called radiation-induced genomic instability, and chemical mutagens. Radiation-induced genomic instability occurs in both germinal and somatic cells and also in the offspring of irradiated individuals, and it is characterised by genetic changes including chromosomal rearrangements. The majority of studies of trans-generational, radiation-induced genomic instability have been described in the male germ line, whereas the authors who have chosen the female as a model are scarce. The aim of this work is to find out the radiation-induced effects in the foetal offspring of X-ray-treated female rats and, at the same time, the possible impact of this radiation-induced genomic instability on the action of a chemical mutagen. In order to achieve both goals, the quantity and quality of chromosomal damage were analysed. In order to detect trans-generational genomic instability, a total of 4806 metaphases from foetal tissues from the foetal offspring of X-irradiated female rats (5 Gy, acute dose) were analysed. The study's results showed that there is radiation-induced genomic instability: the number of aberrant metaphases and the breaks per total metaphases studied increased and were found to be statistically significant (p ≤ 0.05), with regard to the control group. In order to identify how this trans-generational, radiation-induced chromosomal instability could influence the chromosomal behaviour of the offspring of irradiated rat females in front of a chemical agent (aphidicolin), a total of 2481 metaphases were studied. The observed results showed that there is an enhancement of the action of the chemical agent: chromosomal breaks per aberrant metaphases show significant differences (p ≤ 0.05) in the X-ray- and aphidicolin-treated group as regards the aphidicolin-treated group. In conclusion, our findings indicate that there is trans-generational, radiation-induced chromosomal instability in the foetal cells

  7. Trans-generational radiation-induced chromosomal instability in the female enhances the action of chemical mutagens

    Energy Technology Data Exchange (ETDEWEB)

    Camats, Nuria [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, Francisca [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Parrilla, Juan Jose [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, 30120 El Palmar, Murcia (Spain); Calaf, Joaquim [Servei de Ginecologia i Obstetricia, Hospital Universitari de la Santa Creu i Sant Pau, 08025 Barcelona (Spain); Martin, Miguel [Departament de Pediatria, d' Obstetricia i Ginecologia i de Medicina Preventiva, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Caldes, Montserrat Garcia [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain)], E-mail: Montserrat.Garcia.Caldes@uab.es

    2008-04-02

    Genomic instability can be produced by ionising radiation, so-called radiation-induced genomic instability, and chemical mutagens. Radiation-induced genomic instability occurs in both germinal and somatic cells and also in the offspring of irradiated individuals, and it is characterised by genetic changes including chromosomal rearrangements. The majority of studies of trans-generational, radiation-induced genomic instability have been described in the male germ line, whereas the authors who have chosen the female as a model are scarce. The aim of this work is to find out the radiation-induced effects in the foetal offspring of X-ray-treated female rats and, at the same time, the possible impact of this radiation-induced genomic instability on the action of a chemical mutagen. In order to achieve both goals, the quantity and quality of chromosomal damage were analysed. In order to detect trans-generational genomic instability, a total of 4806 metaphases from foetal tissues from the foetal offspring of X-irradiated female rats (5 Gy, acute dose) were analysed. The study's results showed that there is radiation-induced genomic instability: the number of aberrant metaphases and the breaks per total metaphases studied increased and were found to be statistically significant (p {<=} 0.05), with regard to the control group. In order to identify how this trans-generational, radiation-induced chromosomal instability could influence the chromosomal behaviour of the offspring of irradiated rat females in front of a chemical agent (aphidicolin), a total of 2481 metaphases were studied. The observed results showed that there is an enhancement of the action of the chemical agent: chromosomal breaks per aberrant metaphases show significant differences (p {<=} 0.05) in the X-ray- and aphidicolin-treated group as regards the aphidicolin-treated group. In conclusion, our findings indicate that there is trans-generational, radiation-induced chromosomal instability in the foetal

  8. Een onderzoek naar het voorkomen van mutagene en/of carcinogene verbindingen in organische concentraten van Nederlands drinkwater alsmede naar de effecten van diverse zuiveringsstappen op de mutagene activiteit

    NARCIS (Netherlands)

    Kool HJ; van Kreijl CF; Hrubec J; van Oers JAM; Persad S

    1987-01-01

    In drinkwater, bereid uit oppervlaktewater en grondwater werd in veel gevallen mutagene activiteit aangetoond. Duinfiltratie en actiefkool filtratie verwijderen de mutagene activiteit. Chloring verhoogt die activiteit aanzienlijk, chloordioxide in concentraties kleiner dan 1 mg/l C10-2 leidt tot

  9. Determination of the main impurities formed after acid hydrolysis of soybean extracts and the in vitro mutagenicity and genotoxicity studies of 5-ethoxymethyl-2-furfural.

    Science.gov (United States)

    Nemitz, Marina C; Picada, Jaqueline N; da Silva, Juliana; Garcia, Ana Letícia H; Papke, Débora K M; Grivicich, Ivana; Steppe, Martin; von Poser, Gilsane L; Teixeira, Helder F

    2016-09-10

    Soybean acid hydrolyzed extracts are raw-materials widely used for manufacturing of pharmaceuticals and cosmetics products due to their high content of isoflavone aglycones. In the present study, the main sugar degradation products 5-hydroxymethyl-2-furfural (HMF) and 5-ethoxymethyl-2-furfural (EMF) were quantitatively determined after acid hydrolysis of extracts from different soybean cultivars by a validated liquid chromatography method. The furanic compounds determined in samples cover the range of 0.16-0.21mg/mL and 0.22-0.33mg/mL for HMF and EMF, respectively. Complementarily, due to the scarce literature regarding the EMF toxicology, this study also assessed the EMF mutagenicity by the Salmonella/microsome test and genotoxicity by the comet assay. The results revealed that EMF did not show mutagenicity at the range of 50-5000μg/plate in S. typhimurium strains TA98, TA97a, TA100, TA102 and TA1535, but induced DNA damage in HepG2 cells at non-cytotoxic doses of 0.1-1.3mg/mL, mainly by oxidative stress mechanisms. Based on literature of HMF genotoxicity, and considering the EMF genotoxicity results herein shown, purification procedures to remove these impurities from extracts are recommended during healthcare products development to ensure the security of the products. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Experimental study of mutagenous and mitosis modifying activity of silver nanoparticles

    Directory of Open Access Journals (Sweden)

    B. S. Kirbik

    2015-01-01

    Full Text Available Mutagenous and mitosis modifying impact of silver nanoparticles has been studied on outbred mice. Nanoparticles were of round shape with dimensions of 5-50 nm, size of generated organic shell of 2-5 nm, the quantity in 1 mcm3 makes 120-270. Metaphasic analysis of mice bone marrow cells was used as a testing technique. The frequency of chromosome aberrations and mitotic index of preparations were accounted. During single intraperitoneal administration of the agent in the dose of 250 mcg/kg the silver nanoparticles demonstrated mitosis stimulating activity. No mutagenous effect of silver nanoparticles by daily administration for 4 days of 25 mcg/kg and single administration in the dose of 250 mcg/kg has been registered, but there is statistically insignificant tendency of aberrant metaphases increase. Consequently silver nanoparticles in the investigated doses demonstrated no mutagenous activity and can be considered safe for mammalian cells.

  11. Interactive lethal and mutagenic effects of ultraviolet light and bleomycin in yeast: synergism or antagonism?

    Science.gov (United States)

    Lillo, O L; Severgnini, A A; Nunes, E M

    1997-11-01

    The mutagenic interactions of ultraviolet light and bleomycin in haploid populations of Saccharomyces cerevisiae were analyzed. Survival and mutation frequency as a function of different bleomycin concentrations after one conditioning dose of UV radiation were determined. Furthermore, corresponding interaction functions and sensitization factors were calculated. A synergistic interaction between UV light and bleomycin was shown for both lethal and mutagenic events when the cells were in nutrient broth during the treatments. Conversely, the interaction between UV light and bleomycin was antagonistic when the cells were in deionized water during the treatment. The magnitude of lethal and mutagenic interactions depends on dose, and thus presumably on the number of lesions. The observed interactions between UV light and bleomycin suggest that the mechanism that is most likely involved is the induction of repair systems with different error probabilities during the delay of cell division.

  12. [Mutagenic effect of the food-coloring agents tartrazine and indigo carmine].

    Science.gov (United States)

    Karpliuk, I A; Volkova, N A; Okuneva, L A; Gogol', A T; Rybakova, K D

    1984-01-01

    The authors studied the mutagenic action of the food dyes, tartrazine (both Soviet and imported) and indigocarmine in a microbial model and in warm-blooded animals (linear mice). Determined the toxicity and mutagenic action of the dyes on E. coli, strain K-12, carried out chromosomal analysis of the bone marrow, examined the dominant lethals in CBA X C57BL/6 mice. The recommended daily dose amounts to 400 mg/kg for tartrazine and to 50 mg/kg for indigocarmine with regard to the safety factor equal to 100. The data derived as a result of studying the mutagenic activity of tartrazine manufactured in the USSR and CSSR and indigocarmine paste in 3 experimental models allow the conclusion to be made that the doses of these dyes applied in food industry are fairly safe.

  13. Effect of cadmium on genetic toxicity and protection of cortex acanthopanasia radicis against genetic damage induced by cadmium

    International Nuclear Information System (INIS)

    Liu Bing; Pang Huimin; Chen Minyi

    1999-01-01

    Objective and Methods: The test of sperm aberration and micronucleus of bone marrow cells in mice were used to detect the mutagenicity of cadmium and anti-mutagenicity of Cortex Acanthopanasia Radicis (CAR) on germ cell and somatic cell. Kunming mice were divided randomly into four groups: normal saline control group (NS): MMC control group (MMC 1.0 mg/kg); Cd-mutate group (1/5 LD 50 ), 17.6 mg/kg); CAR anti-mutate group (CAR 1,2,4 g/kg + Cd). Ridit test and x 2 were used to evaluate the statistical significance of the date. Results: The experiment demonstrated that Chinese medicine CAR can significantly decrease sperm aberration and micronuclei frequencies induced by Cd (P<0.01). Conclusion: As an anti-mutagen CAR has practical value in occupational protection against genetic damage induced by Cd

  14. UV-induced skin damage

    International Nuclear Information System (INIS)

    Ichihashi, M.; Ueda, M.; Budiyanto, A.; Bito, T.; Oka, M.; Fukunaga, M.; Tsuru, K.; Horikawa, T.

    2003-01-01

    Solar radiation induces acute and chronic reactions in human and animal skin. Chronic repeated exposures are the primary cause of benign and malignant skin tumors, including malignant melanoma. Among types of solar radiation, ultraviolet B (290-320 nm) radiation is highly mutagenic and carcinogenic in animal experiments compared to ultraviolet A (320-400 nm) radiation. Epidemiological studies suggest that solar UV radiation is responsible for skin tumor development via gene mutations and immunosuppression, and possibly for photoaging. In this review, recent understanding of DNA damage caused by direct UV radiation and by indirect stress via reactive oxygen species (ROS) and DNA repair mechanisms, particularly nucleotide excision repair of human cells, are discussed. In addition, mutations induced by solar UV radiation in p53, ras and patched genes of non-melanoma skin cancer cells, and the role of ROS as both a promoter in UV-carcinogenesis and an inducer of UV-apoptosis, are described based primarily on the findings reported during the last decade. Furthermore, the effect of UV on immunological reaction in the skin is discussed. Finally, possible prevention of UV-induced skin cancer by feeding or topical use of antioxidants, such as polyphenols, vitamin C, and vitamin E, is discussed

  15. An Evaluation of the Mode of Action Framework for MutagenicCarcinogens Case Study II: Chromium (VI).

    Science.gov (United States)

    In response to the 2005 revised U.S Environmental Protection Agency’s (EPA) Cancer Guidelines, a strategy is being developed to include all mutagenicity and other genotoxicity data with any additional information to determine whether a carcinogen operates through a mutagenic mode...

  16. ASCORBIC ACID REDUCTION OF ACTIVE CHLORINE PRIOR TO DETERMINING AMES MUTAGENICITY OF CHLORINATED NATURAL ORGANIC MATTER (NOM)

    Science.gov (United States)

    Many potable water disinfection byproducts (DBPs) that result from the reaction of natural organic matter (NOM) with oxidizing chlorine are known or suspected to be carcinogenic and mutagenic. The Ames assay is routinely used to assess an overall level of mutagenicity for all com...

  17. Mutagenic effects of 3-carbethoxypsoralen and 8-methoxypsoralen plus 365-nm irradiation in mammalian cells

    International Nuclear Information System (INIS)

    Papadopoulo, D.; Sagliocco, F.; Averbeck, D.

    1983-01-01

    Cell survival, i.e. colony-forming ability, and the induction of 6-thioguanine-resistant (6-TGsup(r)) mutants were determined in Chinese hamster V79 cells by using two photoreactive furocoumarins of photochemotherapeutic interest: the bifunctional compound 8-methoxypsoralen (8-MOP) and the monofunctional compound 3-carbethoxypsoralen (3-CPs). To quantify the mutation induction in V79 cells mutants deficient in the enzyme hypoxanthine-guanine phosphoribosyl transferase (HGPRT) were selected with the purine analogue 6-thioguanine (6-TG). Both compounds exhibited lethal and mutagenic activities but the monofunctional compound 3-CPs was less lethal and mutagenic than the bifunctional compound 8-MOP. (Auth.)

  18. Mutagenic action of radiation with different LET on Bacillus subtilis cells

    International Nuclear Information System (INIS)

    edinennyj Inst. Yadernykh Issledovanij, Dubna (Russian Federation))" data-affiliation=" (Obedinennyj Inst. Yadernykh Issledovanij, Dubna (Russian Federation))" >Borejko, A.V.; edinennyj Inst. Yadernykh Issledovanij, Dubna (Russian Federation))" data-affiliation=" (Obedinennyj Inst. Yadernykh Issledovanij, Dubna (Russian Federation))" >Krasavin, E.A.

    1997-01-01

    The induction of the his - -> his + mutants in vegetative and spores of Bacillus subtilis wild type cells irradiated with γ-rays and helium ions (LET = 20-80 keV/μm) has been investigated. It was shown that the dose dependence of the mutation induction in vegetative cells is described by a linear-quadratic function of dose in case of both γ-rays and helium ions. RBE (LET) dependencies on the lethal and mutagenic effect of radiation have a local maximum. The maximum of RBE (LET) dependence on the mutagenic assay is shifted at the low region of LET in comparison with the lethal effect of irradiation. (author)

  19. Radiosensitization, mutagenicity, and toxicity of Escherichia coli by several nitrofurans and nitroimidazoles. [X radiation

    Energy Technology Data Exchange (ETDEWEB)

    Chessin, H.; McLaughlin, T.; Mroczkowski, Z.; Rupp, W.D.; Low, K.B.

    1978-08-01

    Representative nitrofurans (nitrofurantoin, nifuroxime, NF-167, NF-269) and nitroimidazoles (metronidazole, misonidazole) were found to sensitize hypoxic RecA/sup -/ Escherichia coli cells to X irradiation. These compounds were also mutagenic to E. coli using a UvrA/sup -/ strain as a test system, and toxic at high concentrations, using several strains differing in their repair capacity. However, the relative degrees of radiosensitization, mutagenicity, and toxicity, for the various compounds, were not simply correlated, suggesting that potential radiosensitizers with fewer side effects could be screened using bacteria.

  20. Suppressive effects of coffee on the SOS responses induced by UV and chemical mutagens

    International Nuclear Information System (INIS)

    Obana, Hirotaka; Nakamura, Sei-ichi; Tanaka, Ryou-ichi

    1986-01-01

    SOS-inducing activity of UV or chemical mutagens was strongly suppressed by instant coffee in Salmonella typhimurium TA1535/pSK1002. As decaffeinated instant coffee showed a similarly strong suppressive effect, it would seem that caffeine, a known inhibitor of SOS responses, is not responsible for the effect observed. The suppression was also shown by freshly brewed coffee extracts. However, the suppression was absent in green coffee-bean extracts. These results suggest that coffee contains some substance(s) which, apart from caffeine, suppresses SOS-inducing activity of UV or chemical mutagens and that the suppressive substance(s) are produced by roasting coffee beans. (Auth.)

  1. The changeability of Pyricularia oryzae Cav. 1. The action of some mutagenous factors

    International Nuclear Information System (INIS)

    Voinova, T.M.; Terekhova, V.A.; D'yakov, Yu.T.

    1983-01-01

    The lethal and mutagenous actions of UV rays, nitrozomethylurea, and nitrosoguanidine in respect to Conidia of rice Pyricularia oryzae Cav. agent have been investigated. It has been found out that low doses of UV-radiation, which are not lethal for a three-cell conidia, increase the intensity of two-cell vegetation. All the investigated mutagens cause a formation of mutants which are deficient according to pigment synthesis white and pink colonies and differ by their reduced growth. Auxotrophic mutants were mainly obtained under the action of nitroso compounds

  2. Investigation of mutagenicity of extracts of hydrobionts from lake Drukshiai and water from its streamlets

    International Nuclear Information System (INIS)

    Lekevichius, R.; Dagyte, B.; Sabaliuniene, I.; Shumyliene, I.; Mishkelevichiute, E.

    1995-01-01

    Rain-water samples from Ignalina NPP buildings and industry sewerage water samples collected in 1993-1994 induced statistically significant increase in levels of frameshift and and base-substitution mutations in Salmonella typhimurium Ames tester strains. It was found that mutagens originated not by Ignalina NPP get into lake Drukshiai from its streamlets. Extracts from 4 species of molluscs did not induce frameshift and base-substitution mutations in Ames tester-strains. Among extracts of liver, muscles and gonads from 4 fish species tested, the highest mutagenicity levels were induced by extracts of gonads from the largest fish. (author). 4 refs., 4 tabs

  3. Influence of mutagens on enzymes of germinating seeds of cotton (Gossypium hirsutum L.)

    International Nuclear Information System (INIS)

    Muthusamy, A.; Jayabalan, N.; Juliana, B.

    2000-01-01

    The activities of the enzymes amylases, protease and phosphatases were studied in cotton during germination. The seeds were treated with 100-500 Gy of gamma rays, 10-50 mM of EMS, CA and SA in two cultivated varieties viz.. MCU 5 and MCU 11. Activity pattern of amylases, protease and phosphatases in treated seeds were significantly altered from controls. The alteration were positively correlated with increasing dose/concentration of mutagens up to 300 Gy of gamma rays and 30 mM of EMS, CA and SA. The present study pave the ways to discuss the importance of the enzymes and mutagens in germination of cotton seeds. (author)

  4. Genotoxic damage in non-irradiated cells: contribution from the bystander effect

    International Nuclear Information System (INIS)

    Zhou, H.; Randers-Pherson, G.; Suzuki, M.; Waldren, C.A.; Hei, T.K.

    2002-01-01

    It has always been accepted dogma that the deleterious effects of ionising radiation such as mutagenesis and carcinogenesis are due mainly to direct damage to DNA. Using the Columbia University charged-particle microbeam and the highly sensitive A L cell mutagenic assay, it is shown here that non-irradiated cells acquire the mutagenic phenotype through direct contact with cells whose nuclei are traversed with 2 alpha particles each. Pre-treatment of cells with lindane, a gap junction inhibitor, significantly decreased the mutant yield. Furthermore, when irradiated cells were mixed with control cells in a similar ration as the in situ studies, no enhancement in bystander mutagenesis was detected. Our studies provide clear evidence that genotoxic damage can be induced in non-irradiated cells, and that gap junction mediated cell-cell communication plays a critical role in the bystander phenomenon. (author)

  5. Earthquake damage to underground facilities

    International Nuclear Information System (INIS)

    Pratt, H.R.; Hustrulid, W.A.; Stephenson, D.E.

    1978-11-01

    The potential seismic risk for an underground nuclear waste repository will be one of the considerations in evaluating its ultimate location. However, the risk to subsurface facilities cannot be judged by applying intensity ratings derived from the surface effects of an earthquake. A literature review and analysis were performed to document the damage and non-damage due to earthquakes to underground facilities. Damage from earthquakes to tunnels, s, and wells and damage (rock bursts) from mining operations were investigated. Damage from documented nuclear events was also included in the study where applicable. There are very few data on damage in the subsurface due to earthquakes. This fact itself attests to the lessened effect of earthquakes in the subsurface because mines exist in areas where strong earthquakes have done extensive surface damage. More damage is reported in shallow tunnels near the surface than in deep mines. In mines and tunnels, large displacements occur primarily along pre-existing faults and fractures or at the surface entrance to these facilities.Data indicate vertical structures such as wells and shafts are less susceptible to damage than surface facilities. More analysis is required before seismic criteria can be formulated for the siting of a nuclear waste repository

  6. Mutagenic activity of 2-(2',4'-diaminophenoxy)ethanol in strains TA1538 and TA98 of Salmonella typhimurium.

    Science.gov (United States)

    Mohn, G; Bouter, S; de Knijff, P

    1982-12-01

    The mutagenicity of 2-(2',4'-diaminophenoxy)ethanol (2,4-DAPE) was compared with that of 2,4-diaminoanisole (2,4-DAA), a chemically related compound previously used in hair-dye formulations. Both chemicals were tested in standard procedures with the Salmonella/microsome mutagenicity test as described by Ames and colleagues. In several experiments, which extended over a total period of 2 years, 2,4-DAA exhibited definite, but variable mutagenicity toward strain TA1538 when S9 preparations of rat liver induced with Aroclor 1254 were present in the incubation mixtures. The compound 2,4-DAPE did not exhibit detectable mutagenic activity when tested concomitantly under the same experimental conditions. We conclude that 2,4-DAPE is not mutagenic for Salmonella under conditions of the standard mammalian microsome assay with strain TA1538 and TA98 as indicators.

  7. Some aspects of the combined mutagenic utilization of ionizing radiation and chemical mutagens in the experimental mutagenesis with Chlorella vulgaris B

    International Nuclear Information System (INIS)

    Mekhandzhiev, A.D.; Chankova, S.G.; Petkova, S.D.

    1979-01-01

    The influence of mutagen dose and cell cycle phase in combined mutagenic effects of ionizing radiation and EMS was experimentally studied on Chlorella vulgaris B. The duration of the cell cycle phases was determined from autoradiographic data on the kinetics of the incorporated labelled precursor ( 3 H-thymidine). The mutagenic effect was evaluated on the 10th or 11th day by the induced pigment mutations on a total of 450,105 colonies. It was found that the combining of 2, 6 or 15 krad gamma rays with EMC in doses 0.002, 0.125 or 0.5 M on the 4th, 12th, 11th, 16th or 18th hour of the cell cycle has a different effect, depending on mutagen dose and cell cycle phase. In this way, combining three different doses of gamma rays with 0.5 M EMC(LDsub(90-99)) at the onset of G 1 induces a distinct rise in the percentage of pigment mutations, as compared to the theoretically expected. The superadditive effect in this case however was associated with limitation of the mutation spectrum. Treatment with average lethal combination (6 krad gamma rays + 0.002 M EMC or 6 krad gamma rays + 0.125 M EMC) was not very effective, but the induced mutations had a rather broader spectrum (8-9 types). A comparison of the theoretically expected yield of pigment mutations with the actually obtained one shows a superadditibility only in cells treated in G 1 (LD 60 ) and in the mid S-phase (LD 40 ). (A.B.)

  8. Resveratrol Ameliorates Tau Hyperphosphorylation at Ser396 Site and Oxidative Damage in Rat Hippocampal Slices Exposed to Vanadate: Implication of ERK1/2 and GSK-3β Signaling Cascades.

    Science.gov (United States)

    Jhang, Kyoung A; Park, Jin-Sun; Kim, Hee-Sun; Chong, Young Hae

    2017-11-08

    The objective of this study was to investigate the effect of resveratrol (a natural polyphenolic phytostilbene) on tau hyperphosphorylation and oxidative damage induced by sodium orthovanadate (Na 3 VO 4 ), the prevalent species of vanadium (vanadate), in rat hippocampal slices. Our results showed that resveratrol significantly inhibited Na 3 VO 4 -induced hyperphosphorylation of tau at the Ser396 (p-S396-tau) site, which is upregulated in the hippocampus of Alzheimer's disease (AD) brains and principally linked to AD-associated cognitive dysfunction. Subsequent mechanistic studies revealed that reduction of ERK1/2 activation was involved in the inhibitory effect of resveratrol by inhibiting the ERK1/2 pathway with SL327 mimicking the aforementioned effect of resveratrol. Moreover, resveratrol potently induced GSK-3β Ser9 phosphorylation and reduced Na 3 VO 4 -induced p-S396-tau levels, which were markedly replicated by pharmacologic inhibition of GSK-3β with LiCl. These results indicate that resveratrol could suppress Na 3 VO 4 -induced p-S396-tau levels via downregulating ERK1/2 and GSK-3β signaling cascades in rat hippocampal slices. In addition, resveratrol diminished the increased extracellular reactive oxygen species generation and hippocampal toxicity upon long-term exposure to Na 3 VO 4 or FeCl 2 . Our findings strongly support the notion that resveratrol may serve as a potential nutraceutical agent for AD.

  9. Repair of DNA damage induced by anthanthrene, a polycyclic aromatic hydrocarbon (PAH) without bay or fjord regions

    DEFF Research Database (Denmark)

    Madsen, Claus Desler; Johannessen, Christian; Rasmussen, Lene Juel

    2009-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants, formed during incomplete burning of coal, oil and gas. Several PAHs have carcinogenic and mutagenic potencies, but these compounds must be activated in order to exert their mutagenic effects. One of the principal pathways...... proposed for metabolic activation of PAHs involves the cytochrome P450 enzymes. The DNA damaging potential of cytochrome P450-activated PAHs is generally associated with their bay and fjord regions, and the DNA repair response of PAHs containing such regions has been thoroughly studied. However, little...... in response to DNA damage induced by cytochrome P450-activated anthanthrene. In cell extracts, functional nucleotide excision repair (NER) and mismatch repair (MMR) activities were necessary to trigger a response to anthanthrene metabolite-induced DNA damage. In cell cultures, NER was responsible...

  10. Human hepatoma cells exposed to estuarine sediment contaminant extracts permitted the differentiation between cytotoxic and pro-mutagenic fractions

    International Nuclear Information System (INIS)

    Pinto, M.; Costa, P.M.; Louro, H.; Costa, M.H.; Lavinha, J.

    2014-01-01

    Complex toxicant mixtures present in estuarine sediments often render contaminant screening unfeasible and compromise determining causation. HepG2 cells were subjected to bioassays with sediment extracts obtained with a series of progressively polar solvents plus a crude extract. The sediments were collected from an impacted area of an estuary otherwise regarded as pristine, whose stressors result mostly from aquaculture effluents and hydrodynamic shifts that enhance particle deposition. Compared to a reference scenario, the most polar extracts yielded highest cytotoxicity while higher genotoxicity (including oxidative damage) was elicited by non-polar solvents. While the former caused effects similar to those expected from biocides, the latter triggered effects compatible with known pro-mutagens like PAHs, even though the overall levels of toxicants were considered of low risk. The results indicate that the approach may constitute an effective line-of-evidence to infer on the predominant set of hazardous contaminants present in complex environmental mixtures. -- Highlights: • Estuarine sediment contaminants were extracted with different organic solvents. • More polar solvents contained the most cytotoxic contaminant fraction. • Non-polar solvents extracted the main genotoxic component of the mixture. • DNA base oxidation was detected through FPG/Comet assay. • The contamination pattern could be inferred from cytoassays with HepG2 cells. -- Polar/non-polar sediment fractions elicited differential cytotoxic and genotoxic effects in human HepG2 cells

  11. Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa L).

    Science.gov (United States)

    Liju, Vijayasteltar B; Jeena, Kottarapat; Kuttan, Ramadasan

    2013-03-01

    The present study investigated the acute, subchronic and genotoxicity of turmeric essential oil (TEO) from Curcuma longa L. Acute administration of TEO was done as single dose up to 5 g of TEO per kg body weight and subchronic toxicity study for thirteen weeks was done by daily oral administration of TEO at doses 0.1, 0.25 and 0.5 g/kg b.wt. in Wistar rats. There were no mortality, adverse clinical signs or changes in body weight; water and food consumption during acute as well as subchronic toxicity studies. Indicators of hepatic function such as aspartate aminotransferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) were unchanged in treated animals compared to untreated animals. Oral administration of TEO for 13 weeks did not alter total cholesterol, triglycerides, markers of renal function, serum electrolyte parameters and histopathology of tissues. TEO did not produce any mutagenicity to Salmonella typhimurium TA-98, TA-100, TA-102 and TA-1535 with or without metabolic activation. Administration of TEO to rats (1 g/kg b.wt.) for 14 days did not produce any chromosome aberration or micronuclei in rat bone marrow cells and did not produce any DNA damage as seen by comet assay confirming the non toxicity of TEO. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. SOS gene induction and possible mutagenic effects of freeze-drying in Escherichia coli and Salmonella typhimurium.

    Science.gov (United States)

    Rosen, Rachel; Buchinger, Sebastian; Pfänder, Ramona; Pedhazur, Rami; Reifferscheid, Georg; Belkin, Shimshon

    2016-11-01

    We report the results of a study of the potential negative effects of the freeze-drying process, normally considered a benign means for long-term conservation of living cells and the golden standard in bacterial preservation. By monitoring gene induction using a whole-cell Escherichia coli bioreporter panel, in which diverse stress-responsive gene promoters are fused to luminescent or fluorescent reporting systems, we have demonstrated that DNA repair genes belonging to the SOS operon (recA, sulA, uvrA, umuD, and lexA) were induced upon resuscitation from the freeze-dried state, whereas other stress-responsive promoters such as grpE, katG, phoA, soxS, and sodA were not affected. This observation was confirmed by the UMU-chromotest (activation of the umuD gene promoter) in Salmonella typhimurium, as well as by real-time PCR analyses of selected E. coli SOS genes. We further show that a functional SOS operon is important in viability maintenance following resuscitation, but that at the same time, this repair system may introduce significantly higher mutation rates, comparable to those induced by high concentrations of a known mutagen. Our results also indicate that the entire freeze-drying process, rather than either freezing or drying separately, is instrumental in the induction of DNA damage.

  13. Development and applications of Bacillus subtilis test systems for mutagens, involving DNA-repair deficiency and suppressible auxotrophic mutations

    International Nuclear Information System (INIS)

    Tanooka, H.

    1977-01-01

    A mutagen-tester of Bacillus subtilis was constructed and tested with known carcinogens. The parental strain HA101 of Okubo and Yanagida carrying suppressible nonsense mutations in his and met genes was transformed to carry an excision-repair deficiency mutation. The constructed strain TKJ5211 showed a 20-30-fold higher sensitivity for His + reversion than the parental strain when treated with UV and UV-mimetic chemicals but unchanged mutation frequency with X-rays and methyl methanesulfonate. The tester strain was used in a spot test of 30 selected chemicals and also for testing with liver homogenate activation. The results showed an almost equivalent but somewhat broader detection spectrum than the Salmonella typhimurium TA100 system. Another test method used a pair of B. subtilis strains differing in their DNA-repair capacity, i.e. the most UV-sensitive mutant HJ-15 and a wild-type strain, to detect repair-dependent DNA damage produced by chemicals. Spores could be used in either test

  14. Fungal flora of Egyptian baladi bread with special reference to the mutagenic effects of their toxic metabolites.

    Science.gov (United States)

    Megalla, S E; Abdou, R F; Bagy, M M

    1985-01-01

    The fungal flora of wheat flour and baladi bread in upper Egypt were investigated. Most of the isolated fungal species belong to the genus Aspergillus. The presence of non heat resistant fungi of the both flat surfaces of baladi bread, came from contamination after baking and from improper handling at homes. Among the heat resistant fungi, A. fumigatus and A. niger, were recorded to inhabit the spongy crumb although the high temperature of baking process which reached approximately 100 degrees C in the center of the bread. The mutagenic effects of the fungal metabolites of the extract of mouldy Egypt were investigated. Most of the isolated fungal species all stages of mitotic division. The most interesting effect of these fungal metabolites were the induction of tripolar and quadripolar spindle. Multinucleate and polyploid cells were also observed under relatively high concentrations. It was noticed that at either higher concentrations or lower concentrations with long exposure, damaged cells were observed. The hazards involved through the consumption of individuals to such mouldy bread, is accumulation of possible deleterious effects from both long and short term exposure to these toxic metabolites.

  15. Radiation damage in DNA

    International Nuclear Information System (INIS)

    Lafleur, V.

    1978-01-01

    A number of experiments are described with the purpose to obtain a better insight in the chemical nature and the biological significance of radiation-induced damage in DNA, with some emphasis on the significance of alkali-labile sites. It is shown that not only reactions of OH radicals but also of H radicals introduce breaks and other inactivating damage in single-standed phiX174 DNA. It is found that phosphate buffer is very suitable for the study of the reactions of H radicals with DNA, as the H 2 PO 4 - ions convert the hydrated electrons into H radicals. The hydrated electron, which does react with DNA, does not cause a detectable inactivation. (Auth.)

  16. Investigation of the induction of oxidative DNA damage by means of an enzyme-linked immunosorbent assay (ELISA) for thymine glycol containing DNA

    International Nuclear Information System (INIS)

    Pohlenz-Michel, C.

    1988-01-01

    The report explains an ELISA test system for the detection and quantification of toxic effects on genes, induced by mutagenic or carcinogenic chemicals introduced by way of reactive oxygen species. Sensitivity and reproducibility are defined, and the system's applicability to the detection of oxidative DNA damage as a result of the metabolism of chemicals in cellular systems is discussed. (TRV) [de

  17. Updated synthesis of the knowledge about the impact on marine environment of the radioactive releases from Fukushima Dai-ichi damaged site - October 26, 2011; Synthese actualisee des connaissances relatives a l'impact sur le milieu marin des rejets radioactifs du site nucleaire accidente de Fukushima Dai-ichi - 26 octobre 2011

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-10-26

    A strong radioactive contamination of the marine environment close to the damaged Fukushima Dai-ichi power plant has been observed since March 21. The high concentration of some nuclides ({sup 131}I, {sup 137}Cs, {sup 134}Cs, {sup 136}Cs, {sup 132}Te, {sup 132}I) comes from three possible sources: the liquid effluents from the damaged site, the atmospheric fallouts, and the weathering of contaminated soils. This information note presents and comments the most recent informations gathered by the French institute of radiation protection and nuclear safety (IRSN) since the previous information note from July 11 and devoted to the same topic. It presents the estimation of the relative contribution of each contamination source and the evolution with time of the marine contamination. The mapping of {sup 137}Cs concentrations in surface seawater allows to estimate the amount of total {sup 137}Cs in the marine environment and its evolution with time. {sup 137}Cs and {sup 134}Cs concentrations were measured both in samples of surface coastal sediments and in river fishes and seafood products (mainly fishes and molluscs). Results are reported in graphs showing their evolution with time. (J.S.)

  18. Hydrogeologic characterization and evolution of the 'excavation damaged zone' by statistical analyses of pressure signals: application to galleries excavated at the clay-stone sites of Mont Terri (Ga98) and Tournemire (Ga03)

    International Nuclear Information System (INIS)

    Fatmi, H.; Ababou, R.; Matray, J.M.; Joly, C.

    2010-01-01

    Document available in extended abstract form only. This paper presents methods of statistical analysis and interpretation of hydrogeological signals in clayey formations, e.g., pore water pressure and atmospheric pressure. The purpose of these analyses is to characterize the hydraulic behaviour of this type of formation in the case of a deep repository of Mid- Level/High-Level and Long-lived radioactive wastes, and to study the evolution of the geologic formation and its EDZ (Excavation Damaged Zone) during the excavation of galleries. We focus on galleries Ga98 and Ga03 in the sites of Mont Terri (Jura, Switzerland) and Tournemire (France, Aveyron), through data collected in the BPP- 1 and PH2 boreholes, respectively. The Mont Terri site, crossing the Aalenian Opalinus clay-stone, is an underground laboratory managed by an international consortium, namely the Mont Terri project (Switzerland). The Tournemire site, crossing the Toarcian clay-stone, is an Underground Research facility managed by IRSN (France). We have analysed pore water and atmospheric pressure signals at these sites, sometimes in correlation with other data. The methods of analysis are based on the theory of stationary random signals (correlation functions, Fourier spectra, transfer functions, envelopes), and on multi-resolution wavelet analysis (adapted to nonstationary and evolutionary signals). These methods are also combined with filtering techniques, and they can be used for single signals as well as pairs of signals (cross-analyses). The objective of this work is to exploit pressure measurements in selected boreholes from the two compacted clay sites, in order to: - evaluate phenomena affecting the measurements (earth tides, barometric pressures..); - estimate hydraulic properties (specific storage..) of the clay-stones prior to excavation works and compare them with those estimated by pulse or slug tests on shorter time scales; - analyze the effects of drift excavation on pore pressures

  19. Studies on chemical and physical mutagens' induced polygenic variability in mungbean (Vigna radiata (L.) Wilczek)

    International Nuclear Information System (INIS)

    Sangwan, H.P.S.; Singh, M.P.

    1990-01-01

    Full text: Pulses used to be and still are cultivated on marginal lands under poor management conditions which result in low production. Genotypes which could respond to better management have been eliminated by past selection. It is, therefore, difficult and challenging to breed high yielding varieties in pulse crops with the limited genetic variability available. Induced mutations could supplement this variability. Extensive studies on genotype-mutagen interaction were undertaken with six varieties of mungbean having contrasting seed characteristics, morphological traits and genetic backgrounds. Each variety was treated with 300 Gy and 600 Gy of gamma rays, 0.1 and 0.5% of EMS, and 0.1 and 0.05 of SA. Dry seeds, water soaked and phosphate buffer soaked seeds served as controls. The following observations were made: differential response of varieties to mutagen treatments - irrespective of the variety or the characters; gamma-rays proved to be more effective than chemical mutagens; mutagenic treatments resulted in development of early maturing mutants that can fit well in multiple cropping systems particularly in raising a mung crop after the wheat harvest. The fact that some mutants were detected in M 4 with significant increase in yield and marginal improvement in protein content generation suggests the possibility of improving both characters provided a large population is screened. (author)

  20. Mutagenicity assessment of aerosols in emissions from wood combustion in Portugal.

    Science.gov (United States)

    Vu, B; Alves, C A; Gonçalves, C; Pio, C; Gonçalves, F; Pereira, R

    2012-07-01

    Polycyclic aromatic hydrocarbon (PAH) extracts of fine particles (PM(2.5)) collected from combustion of seven wood species and briquettes were tested for mutagenic activities using Ames test with Salmonella typhimurium TA98 and TA100. The woods were Pinus pinaster (maritime pine), Eucalyptus globulus (eucalypt), Quercus suber (cork oak), Acacia longifolia (golden wattle), Quercus faginea (Portuguese oak), Olea europea (olive), and Quercus ilex rotundifolia (Holm oak). Burning experiments were done using woodstove and fireplace, hot start and cold start conditions. A mutagenic response was recorded for all species except golden wattle, maritime pine, and briquettes. The mutagenic extracts were not correlated with high emission factors of carcinogenic PAHs. These extracts were obtained both from two burning appliances and start-up conditions. However, fireplace seemed to favour the occurrence of mutagenic emissions. The negative result recorded for golden wattle was interesting, in an ecological point of view, since after confirmation, this invasive species, can be recommended for domestic use. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Intercellular distribution of mutations induced in oopcytes of Drosophila melanogaster by chemical and physical mutagens

    International Nuclear Information System (INIS)

    Traut, H.

    1979-01-01

    When females of Drosophila melanogaster are treated with chemical or physical mutagens, not only in one but also in both of the two homologous X chromosomes of a given oocyte, a recessive sex-linked lethal mutation may be induced. A method is described that discriminates between such single and double mutations. A theory is developed to show how a comparison betweeen the expected and the observer frequency of double mutations yields an indication of the intercellular distribution (random or nonrandom) of recessive lethal mutations induced by mutagenic agents in oocytes and, consequently, of the distribution (homogenous or nonhomogeneous) of those agents. Three agents were tested: FUdR (12.5, 50.0 and 81.0 μg/ml), mitomycin C (130.0 μg/ml) and x rays (2000 R, 150 kV). After FUdR feeding, no increase in the mutation frequency usually observed in D. melanogaster without mutagenic treatment was obtained (u = 0.13%, namely three single mutations among 2332 chromosomes tested). After mitomycin C feeding 104 single and three double mutations were obtained. All of the 50 mutations observed after x irradiation were single mutations. The results obtained in the mitomycin C and radiation experiments favor the assumption of a random intercellular distribution of recessive lethal mutations induced by these two agents in oocytes of D. melanogaster. Reasons are discussed why for other types of mutagenic agents nonrandom distributions may be observed with our technique

  2. [In vivo mutagenicity and clastogenicity of ionizing radiation in nuclear medicine

    International Nuclear Information System (INIS)

    1989-01-01

    The overall goals of our research remains to investigate the mutagenic and clastogenic effects of exposure to low levels of ionizing radiation in human lymphocytes. We are studying hospital patients referred to a nuclear medicine department for diagnostic cardiac imaging and nuclear medicine technologists who administer radionuclides

  3. MUTAGENICITY OF NITRITE-TREATED AQUEOUS EXTRACT OF 'PIPER BETLE'; L

    Science.gov (United States)

    Betel quid is chewed as a masticatory material by people in certain areas of Asia. The quid chewing has been related to oral cancer by epidemiological study. The mutagenic components in the aqueous extracts of betel quid ingredients were studied. Only nitrite-treated aqueous extr...

  4. The inactivating and mutagenic effect of hydroxylamine on bacteriophage φX174

    NARCIS (Netherlands)

    Pol, J.H. van de; Arkel, G.A. van

    1965-01-01

    The inactivation of bacteriophage ΦXI74 by the mutagenic agents nitrous acid and ultraviolet irradiation proceeds according to a single-hit kinetics. However, treatment of purified ΦXI74 by hydroxylamine (HA) at pH 6 and 25° results in an inactivation that is not strictly exponential. The

  5. Quantitative changes in endogenous DNA adducts correlate with conazole mutagenicity and tumorigenicity in mouse liver.**

    Science.gov (United States)

    We have previously shown that the conazole fungicides triadimefon and propiconazole, which are tumorigenic in mouse liver, are in vivo mouse liver mutagens in the Big Blue" transgenic mutation assay when administered in feed at tumorigenic doses. The nontumorigenic conazole myclo...

  6. Quantitative changes in endogenous DNA adducts correlate with conazole mutagenicity and tumorigenicity in mouse liver.

    Science.gov (United States)

    We have previously shown that the conazole fungicides triadimefon and propiconazole, which are tumorigenic in mouse liver, are in vivo mouse liver mutagens in the Big Blue" transgenic mutation assay when administered in feed at tumorigenic doses. The nontumorigenic conazole myclo...

  7. An evaluation of the mode of action framework for mutagenic carcinogens: Chromium (VI): SOT.

    Science.gov (United States)

    In response to the 2005 revised U.S Environmental Protection Agency’s (EPA) Cancer Guidelines, a strategy is being developed to determine whether a carcinogen operates through a mutagenic mode of action (MOA). This information is necessary for EPA to decide whether age-dependent ...

  8. An evaluation of the mode of action framework for mutagenic carcinogens: chromium (VI)

    Science.gov (United States)

    In response to the 2005 revised U.S Environmental Protection Agency’s (EPA) Cancer Guidelines, a strategy is being developed to determine whether a carcinogen operates through a mutagenic mode of action (MOA). This information is necessary for EPA to decide whether age-dependent ...

  9. Feasibility of testing DNA repair inhibitors for mutagenicity by a simple method

    International Nuclear Information System (INIS)

    Sideropoulos, A.S.; Specht, S.M.; Jones, M.T.

    1980-01-01

    A simple screening methodology for the determination of mutagenicity of DNA repair inhibitors has been tested in this laboratory. Radiation-resistant E. coli B/r and WP2 hcr + and hcr - are suitable strains for mutagenicity testing. In these strains irradiated with 40-60 ergs/mm 2 , chemicals which interfere with repair of ultraviolet-induced pre-mutational lesions can be shown to enhance significantly the frequency of mutations to streptomycin resistance. This phenomenon is termed 'mutational synergism' [18,20]. We have attempted to apply the procedure for securing data for 'mutational synergism' between ultraviolet (UV) radiation and a number of antimalarial drugs including quinine hydrochloride (50 μg/ml), quinine hydrobromide (50 μg/ml), primaquine diphosphate (50 μg/ml), chloroquine (50 μg/ml), quinine (50 μg/ml) and quinacrine dihydrochloride (25 μg/ml). All drugs tested give synergistic effects with UV light. The synergistic activity ranges from 3- to 35-fold. Quinine and quinacrine dihydrochloride have been found to be much more efficient enhancers of the mutagenic effect of UV than caffeine. In general, we have found that the expression of synergistic action occurs at a concentration well below the minimum inhibitory concentration (MIC) with the drugs tested. The implication of these observations in the establishment of a screening method for the evaluation of the mutagenicity of DNA repair inhibitors is discussed. (orig.)

  10. Carcinogens, Teratogens and Mutagens: Their Impact on Occupational Health, Particularly for Women in Veterinary Medicine.

    Science.gov (United States)

    Milligan, J. E.; And Others

    1983-01-01

    Pregnant women, especially those working in veterinary medicine, face occupational health/disease risks from mutagens, teratogens, and carcinogens. These hazards can be placed into three categories: physical, chemical, and biological. Each of these hazards is discussed with examples. (Author/JN)

  11. Paving asphalt products exhibit a lack of carcinogenic and mutagenic activity.

    Science.gov (United States)

    Goyak, Katy O; McKee, Richard H; Minsavage, Gary D; McGowan, Claude; Daughtrey, Wayne C; Freeman, James J

    2011-10-01

    A paving asphalt and a vacuum residuum (derived from crude oil by atmospheric and subsequent vacuum distillation and used as a blend stock for asphalt) were tested in skin carcinogenesis assays in mice and in optimized Ames assays for mutagenic activity. In the skin cancer tests, each substance was applied twice weekly for 104 weeks to the clipped backs of groups of 50 male C3H mice. Neither the paving asphalt nor the vacuum residuum (30% weight/volume and 75% weight/weight in US Pharmacopeia mineral oil, respectively) produced any tumors. The positive control benzo[a]pyrene (0.05% w/v in toluene) induced tumors in 46 of 50 mice, demonstrating the effectiveness of the test method. Salmonella typhimurium tester strain TA98 was used in the optimized Ames assay to evaluate mutagenic potential. Dimethylsulfoxide (DMSO) extractions of the substances were not mutagenic when tested up to toxic limits. Thus, under the conditions of these studies, neither the paving asphalt nor the vacuum residuum was carcinogenic or mutagenic.

  12. MUTAGENICITY AND DISINFECTION BY-PRODUCTS IN SURFACE DRINKING WATER DISINFECTED WITH PERACETIC ACID

    Science.gov (United States)

    The aims of this research were to study the influence of peracetic acid (PAA) on the formation of mutagens in surface waters used for human consumption and to assess its potential application for the disinfection of drinking water. The results obtained using PAA were compared to ...

  13. Dietary Exposure of Nigerians to Mutagens and Estrogen-Like Chemicals

    Directory of Open Access Journals (Sweden)

    Iyekhoetin Matthew Omoruyi

    2014-08-01

    Full Text Available Food and drinking water are poorly delineated sources of human exposure to chemical food mutagens and endocrine-disrupting chemicals. In this study, we investigated the presence of mutagens and chemicals exhibiting estrogenic activity in the daily diet of Nigerians, using in vitro assays. Commercially processed foods or snacks and various brands of pure water sachets were extracted by solid-phase extraction and liquid-liquid extraction, respectively. Mutagenicity was determined by the conventional Ames test and two complementary assays on two strains of Salmonella (TA 100 and TA 98, while the estrogenic activity was assessed by a yeast bioluminescent assay, using two recombinant yeast strains (Saccharomyces cerevisiae BMAEREluc/ERα and S. cerevisiae BMA64/luc. A third of the food varieties investigated (chin-chin, hamburger, suya and bean cake were mutagenic in all three assays, either in the presence or absence of S9 mix. Of the packed water samples, five out of the sixteen investigated (31%, were found to be estrogenic, with estradiol and bisphenol A equivalents ranging from 0.79 to 44.0 ng/L and 124.2 to 1,000.8 ng/L, respectively. Hence, although the current situation in Nigeria does not appear to be substantially worse than, e.g., in Europe, regular monitoring is warranted in the future.

  14. Diesel exhaust particles are mutagenic in FE1-MutaMouse lung epithelial cells

    DEFF Research Database (Denmark)

    Jacobsen, Nicklas Raun; Møller, Peter; Cohn, Corey Alexander

    2008-01-01

    The particulate phase of diesel engine exhaust is likely carcinogenic. However, the mechanisms of diesel exhaust particles (DEPs) induced mutagenicity/carcinogenicity are still largely unknown. We determined the mutant frequency following eight repeated 72 h incubations with 37.5 or 75 microg...

  15. Feasibility of testing DNA repair inhibitors for mutagenicity by a simple method

    Energy Technology Data Exchange (ETDEWEB)

    Sideropoulos, A S; Specht, S M; Jones, M T [Duquesne Univ., Pittsburgh, PA (USA). Dept. of Biological Sciences

    1980-04-01

    A simple screening methodology for the determination of mutagenicity of DNA repair inhibitors has been tested in this laboratory. Radiation-resistant E. coli B/r and WP2 hcr/sup +/ and hcr/sup -/ are suitable strains for mutagenicity testing. In these strains irradiated with 40-60 ergs/mm/sup 2/, chemicals which interfere with repair of ultraviolet-induced pre-mutational lesions can be shown to enhance significantly the frequency of mutations to streptomycin resistance. This phenomenon is termed 'mutational synergism' (18,20). We have attempted to apply the procedure for securing data for 'mutational synergism' between ultraviolet (UV) radiation and a number of antimalarial drugs including quinine hydrochloride (50 ..mu..g/ml), quinine hydrobromide (50 ..mu..g/ml), primaquine diphosphate (50 ..mu..g/ml), chloroquine (50 ..mu..g/ml), quinine (50 ..mu..g/ml) and quinacrine dihydrochloride (25 ..mu..g/ml). All drugs tested give synergistic effects with UV light. The synergistic activity ranges from 3- to 35-fold. Quinine and quinacrine dihydrochloride have been found to be much more efficient enhancers of the mutagenic effect of UV than caffeine. In general, we have found that the expression of synergistic action occurs at a concentration well below the minimum inhibitory concentration (MIC) with the drugs tested. The implication of these observations in the establishment of a screening method for the evaluation of the mutagenicity of DNA repair inhibitors is discussed.

  16. Discerning the Chemical Composition and Mutagenic Effects of Soy Biodiesel PM

    Science.gov (United States)

    Discerning the Chemical Composition and Mutagenic Effects of Soy Biodiesel PM David G. Nashab, Esra Mutluc, William T. Prestond, Michael D. Haysb, Sarah H. Warrenc, Charly Kingc, William P. Linakb, M. lan Gilmourc, and David M. DeMarinic aOak Ridge Institute for Science and Ed...

  17. Mutagenicity and antimutagenicity of Salacia crassifolia (mart. Ex. Schult. G. Don. evaluated by Ames test

    Directory of Open Access Journals (Sweden)

    C. C. Carneiro

    2017-09-01

    Full Text Available Abstract Salacia crassifolia (Mart. Ex. Schult. G. Don. is a bush which belongs to Celastraceae family and occurs specially in Brazilian Cerrado. Its leaves, stem, seeds and fruits are popularly used for several medicinal purposes, such as antitumoral, antirheumatic, anti-inflammatory and antimicrobial. In this study, the mutagenic and antimutagenic activities of S. crassifolia stem bark fractions (hexane, ethyl acetate and hydroalcoholic were evaluated by the Ames mutagenicity assay in Salmonella typhimurium TA98 and TA100 strains. By the obtained results, all S. crassifolia fractions did not significantly increase the number of prototrophic revertants for histidine (His+ in both S. typhimurium strains tested (p > 0.05, suggesting absence of mutagenicity. Regarding antimutagenicity, the fractions ethyl acetate and hydroalcoholic significantly decreased the number of His+ revertants colonies induced by positive control for strain TA98 (p < 0.05, demonstrating protection against mutagenicity induced by 4-nitroquinolile1-oxide, whereas the hexane fraction did not show antimutagenic effect in this strain. In the TA100 strain, all fractions of S. crassifolia protected DNA against the harmful action of sodium azide, and the hexane fraction exhibited the greatest protection in this work. Thus, it’s possible conclude that the fractions of S. crassifolia tested in this study could be used in chemoprevention.

  18. Mutagenic and antimutagenic activity of food compounds : Application of a dynamic in vitro gastrointestinal model

    NARCIS (Netherlands)

    Krul, Cyrille Anna Maria

    2001-01-01

    Exposure of humans to potential mutagenic and carcinogenic food compounds through the diet is unavoidable. On the other hand, there is epidemiological evidence for antimutagenic and anticarcinogenic properties of food as well (such as vegetables and fruit). The assessment of carcinogenic and cancer

  19. Radiation and chemical mutagen induced somaclonal variations through in vitro organogenesis of cotton (Gossypium hirsutum L.).

    Science.gov (United States)

    Muthusamy, Annamalai; Jayabalan, Narayanasamy

    2014-12-01

    The purpose of the investigation was to induce somaclonal variations by gamma rays (GR), ethylmethane sulphonate (EMS) and sodium azide (SA) during in vitro organogenesis of cotton. The shoot tip explants were irradiated with 5-50 Gray (Gy) GR (Cobalt 60), 0.5-5.0 mM EMS and SA separately, and inoculated on Murashige and Skoog (MS) medium fortified with plant growth regulator (PGR) for organogenesis. The plantlets with well-developed root systems were acclimatized and transferred into the experimental field to screen the somaclonal variations during growth and development. The number of somaclonal variations was observed in growth of irradiated/treated shoot tips, multiplication, plantlet regeneration and growth in vitro and ex vitro. The lower doses/concentrations of mutagenic treatments showed significant enhancement in selected agronomical characters and they showed decreased trends with increasing doses/concentrations of mutagenic agents. The results of the present study revealed the influence of lower doses/concentrations of mutagenic treatments on in vitro and ex vitro growth of cotton plantlets and their significant improvement in agronomical characters which needs further imperative stability analysis. The present observations showed the platform to use lower doses/concentrations of mutagenic agents to induce variability for enhanced agronomical characters, resistant and tolerant cotton varieties.

  20. Ascorbic acid reduced mutagenicity at the HPRT locus in CHO cells against thermal neutron radiation

    International Nuclear Information System (INIS)

    Kinashi, Yuko; Sakurai, Yoshinori; Masunaga, Shinichiro; Suzuki, Minoru; Nagata, Kenji; Ono, Koji

    2004-01-01

    We investigated the biological effects of the long-lived radicals induced following neutron irradiation. It has been reported that radiation-induced long-lived radicals were scavenged by post-irradiation treatment of ascorbic acid (Koyama, 1998). We studied the effects of ascorbic acid acting as a long-lived radical scavenger on cell killing and mutagenicity in Chinese hamster ovary cells against thermal neutrons produced at the Kyoto University Research reactor. Ascorbic acid was added to cells 30 min after neutron irradiation and removed 150 min after irradiation. The biological end point of cell survival was measured by colony formation assay. The mutagenicity was measured by the mutant frequency in the HPRT locus. The post-irradiation treatment of ascorbic acid did not alter the cell killing effect of neutron radiation. However, the mutagenicity was decreased, especially when the cells were irradiated with boron. Our results suggested that ascorbic acid scavenged long-lived radicals effectively and caused apparent protective effects against mutagenicity of boron neutron capture therapy