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.

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)

Mutation of HIV-1 genomes in a clinical population treated with the mutagenic nucleoside KP1461.

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Mullins, James I; Heath, Laura; Hughes, James P; Kicha, Jessica; Styrchak, Sheila; Wong, Kim G; Rao, Ushnal; Hansen, Alexis; Harris, Kevin S; Laurent, Jean-Pierre; Li, Deyu; Simpson, Jeffrey H; Essigmann, John M; Loeb, Lawrence A; Parkins, Jeffrey

2011-01-14

The deoxycytidine analog KP1212, and its prodrug KP1461, are prototypes of a new class of antiretroviral drugs designed to increase viral mutation rates, with the goal of eventually causing the collapse of the viral population. Here we present an extensive analysis of viral sequences from HIV-1 infected volunteers from the first "mechanism validation" phase II clinical trial of a mutagenic base analog in which individuals previously treated with antiviral drugs received 1600 mg of KP1461 twice per day for 124 days. Plasma viral loads were not reduced, and overall levels of viral mutation were not increased during this short-term study, however, the mutation spectrum of HIV was altered. A large number (N = 105 per sample) of sequences were analyzed, each derived from individual HIV-1 RNA templates, after 0, 56 and 124 days of therapy from 10 treated and 10 untreated control individuals (>7.1 million base pairs of unique viral templates were sequenced). We found that private mutations, those not found in more than one viral sequence and likely to have occurred in the most recent rounds of replication, increased in treated individuals relative to controls after 56 (p = 0.038) and 124 (p = 0.002) days of drug treatment. The spectrum of mutations observed in the treated group showed an excess of A to G and G to A mutations (p = 0.01), and to a lesser extent T to C and C to T mutations (p = 0.09), as predicted by the mechanism of action of the drug. These results validate the proposed mechanism of action in humans and should spur development of this novel antiretroviral approach.

Mutation of HIV-1 genomes in a clinical population treated with the mutagenic nucleoside KP1461.

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James I Mullins

2011-01-01

Full Text Available The deoxycytidine analog KP1212, and its prodrug KP1461, are prototypes of a new class of antiretroviral drugs designed to increase viral mutation rates, with the goal of eventually causing the collapse of the viral population. Here we present an extensive analysis of viral sequences from HIV-1 infected volunteers from the first "mechanism validation" phase II clinical trial of a mutagenic base analog in which individuals previously treated with antiviral drugs received 1600 mg of KP1461 twice per day for 124 days. Plasma viral loads were not reduced, and overall levels of viral mutation were not increased during this short-term study, however, the mutation spectrum of HIV was altered. A large number (N = 105 per sample of sequences were analyzed, each derived from individual HIV-1 RNA templates, after 0, 56 and 124 days of therapy from 10 treated and 10 untreated control individuals (>7.1 million base pairs of unique viral templates were sequenced. We found that private mutations, those not found in more than one viral sequence and likely to have occurred in the most recent rounds of replication, increased in treated individuals relative to controls after 56 (p = 0.038 and 124 (p = 0.002 days of drug treatment. The spectrum of mutations observed in the treated group showed an excess of A to G and G to A mutations (p = 0.01, and to a lesser extent T to C and C to T mutations (p = 0.09, as predicted by the mechanism of action of the drug. These results validate the proposed mechanism of action in humans and should spur development of this novel antiretroviral approach.

Effect of combined mutagenic treatments on sensitivity and mutation frequency in rice

International Nuclear Information System (INIS)

Gopinathan Nair, V.

1977-01-01

Rice seeds were subjected to two sets of combination treatments of radiations and NMH. The effects of mutagenic treatments in the M 1 and M 2 generations were recorded and discussed. Mutation frequencies estimated as number of mutations per 100 M 1 years were not higher than the values expected on the basis of additive effects. When estimated as number of mutants per 100 M 2 plants, the frequencies revealed more than additive effects. The synergistic effect on mutant frequencies was due to increase in the segregation ratio of mutants. This effect was more pronounced at the higher dose combinations of fast neutrons and NMH. (author)

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.

Phonic and induced level of mutations and mutagenicity in bioorganisms habitating in the environs of Ignalina APP

International Nuclear Information System (INIS)

Lekevichius, R.; Morkunas, V.; Knabikas, A.

1992-01-01

The investigation of the extracts from the water, mud and hydrobionts of the lake Drukshiai before the construction of the Ignalina atomic power plant (1982-1984) and after its construction enabled to detect the moment of the build-up of mutagens in the hydrobionts (in 1986), when the extracts began to induce spot mutations in Salmonella typhimurium and exchanges of sister chromatids in human leukocytes in vitro. The mutagenicity of rain water, sewerage water and water from the cooler of the atomic power plant to drosophila and Salmonella typhimurium has been detected. The increments of mutations in the populations of Larus ridibundus and Microtus arvalis inhabiting the surroundings of the atomic power plant has not been noticed. (author). 4 figs., 4 refs

Absence of mutagenic effects of a particular Symphytum officinale L. liquid extract in the bacterial reverse mutation assay.

Science.gov (United States)

Benedek, Birgit; Ziegler, Andreas; Ottersbach, Peter

2010-03-01

Comfrey (Symphytum officinale L.) root is traditionally used for the topical treatment of contusions, strains and sprains. Besides allantoin and rosmarinic acid, which are discussed as pharmacologically active principles, the drug contains pyrrolizidine alkaloids (PAs) known for their hepatotoxic, carcinogenic and mutagenic properties. The topical herbal medicinal products Kytta-Salbe f and Kytta-Plasma f contain a PA-free liquid extract from comfrey root as active substance. The aim of this study was to demonstrate the absence of genotoxic effects of this special extract in the bacterial reverse mutation assay (Ames test). Briefly, comfrey root liquid extract was investigated for its ability to induce gene mutations in Salmonella typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 with and without metabolic activation using the mammalian microsomal fraction S9 mix. Reference mutagens were used to check the validity of the experiments. Comfrey root fluid extract showed no biologically relevant increases in revertant colony numbers of any of the five tester strains, neither in the presence nor in the absence of metabolic activation. In conclusion, the comfrey root fluid extract contained in Kytta-Salbe f and Kytta-Plasma f was not mutagenic in the bacterial reverse mutation assay. (c) 2009 John Wiley & Sons, Ltd.

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.

Mutagenic treatments towards increasing the frequency of day-neutral mutations and standardization of procedures for tissue culture, in potato

International Nuclear Information System (INIS)

Upadhya, M.D.; Chandra, R.; Abraham, M.J.

1976-01-01

Various chemical mutagens and gamma radiation have been used on single dormant eyes and true seeds with a view to finding effective mutagenic treatment for the induction of day-length neutral mutants in potato using an effective screening technique for the isolation of day-length neutral mutants. Sodium meta bisulphite (SMS) was found to be an efficient mutagen in inducing mutations for this trait in true seeds although the same concentrations, when used for treating the single tuber eyes proved lethal. Pre-soaking the seeds for 24 hrs prior to treatment with 0.0025M SMS gave highest frequency of the mutants followed by 48 hrs presoaking, indicating a sensitive stage during the cell cycle in true seeds. Other mutagen treatments gave different frequencies of mutations. The highest frequency of day-length neutral mutants was observed when seeds irradiated with 40 Kr of gamma radiation were treated with 0.05M hydrazinium dichloride solution. Screening procedures have also been standardised with the development of synethetic media for the isolation of biochemical mutants at the true seed level. Initial efforts have yielded mutants resistant to LD 100 doses of ethionine. Another aspect of the study was to develop a proper potato callus culture technique. A medium has been developed to produce and maintain callus from potato leaf strips. Efforts on the regeneration of shoot and roots from callus, have so far lead to differentiation of callus to form roots. The ultimate aim of these studies is to develop plantlets from single cell which would form the units of mutation induction and isolation. (author)

Mutagenic effects of gamma rays and EMS on frequency and spectrum of chlorophyll mutations in urdbean (Vigna mungo (L.) Hepper)

International Nuclear Information System (INIS)

Usharani, K.S.; Ananda Kumar, C.R.

2015-01-01

Chlorophyll mutations act as a significant index in the judgment of induced genetic variations in mutagen treated populations. Different types of chlorophyll mutation have been observed in various crop plants. In the current study, the effect of different concentrations (40 kR, 50 kR and 60 kR) of gamma rays, Ethyl Methane Sulphonate (50 mM, 60 mM and 70 mM) in single and combination dose/concentration on the frequency and spectrum of chlorophyll mutation and the effect of VBN 4 urdbean variety to such irradiation dose was observed. Results showed induction of broad spectrum of chlorophyll mutations which included albina, xantha, chlorina and viridis. Among these chlorina type was predominant in all the mutagenic treatments. The albina type of chlorophyll mutants occurred very rarely and was found only at 60 mM of EMS treatment and at 40 kR + 50 mM, 60 kR + 70 mM of combination treatments. Based on the chlorophyll mutation frequency, gamma rays were most effective followed by EMS and combination of treatments. (author)

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

Induction of somatic mutations in ornamental plants by ionizing radiations and chemical mutagens

International Nuclear Information System (INIS)

Desai, B.M.; Abraham, V.

1980-01-01

Improvement in some ornamental plants through induction of somatic mutations by ionizing radiations and chemical mutagens viz. colchicine, EMS and DS has been attempted. Mutants of high ornamental value have been evolved, isolated and multiplied in canna, perennial portulaca, tuberose, bougainvillea, hibiscus, daisy, lilies. These pertain to changes in colour, shape and size of flower and foliage. Procedural details on induction, isolation, stabilisation of the mutants and description of the new characteristics are presented. (author)

Peptide bond-forming reagents HOAt and HATU are not mutagenic in the bacterial reverse mutation test.

Science.gov (United States)

Nicolette, John; Neft, Robin E; Vanosdol, Jessica; Murray, Joel

2016-04-01

The peptide bond-forming reagents 1-hydroxy-7-azabenzotriazole (HOAt, CAS 39968-33-7) and O-(7-Azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU, CAS 148893-10-1) either have structural alerts, unclassified features or are considered out of domain when evaluated for potential mutagenicity with in silico programs DEREK and CaseUltra. Since they are commonly used reagents in pharmaceutical drug syntheses, they may become drug substance or drug product impurities and would need to be either controlled to appropriately safe levels or tested for mutagenicity. Both reagents were tested in the bacterial reverse mutation (Ames) test at Covance, under GLP conditions, following the OECD test guideline and ICH S2(R1) recommendations and found to be negative. Our data show that HOAt and HATU-common pharmaceutical synthesis reagents-are not mutagenic, and can be treated as ordinary drug impurities. © 2016 Wiley Periodicals, Inc.

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

The Mutation Breeding and Mutagenic Effect of Air Plasma on Penicillium Chrysogenum

International Nuclear Information System (INIS)

Gui Fang; Wang Hui; Wang Peng; Liu Hui; Yuan Chengling; Zheng Zhiming; Cai Xiaochun; Hu Yihua

2012-01-01

Low temperature air plasma was used as the mutation tool for penicillin-producing strain Penicillium chrysogenum. The discharge conditions were RF power of 360 W, temperature of 40°C in a sealed chamber, and pressure of 10 Pa to 30 Pa. The result showed that the kinetics of the survival rate followed a typical saddle-shaped curve. Based on a statistic analysis, at the treating duration of 10 min, the positive mutation rate was as high as 37.5% while the negative mutation rate was low. The colonial morphology changed obviously when the plasma treating duration reached or exceeded 45 min. After both primary and secondary screening, a mutant designated as aPc051310 with high productivity of penicillin was obtained, and a strong mutagenic effect on P. chrysogenum was observed in the process. It was proved that after five generations, the mutant aPc051310 still exhibits a high productivity. All the results prove that the plasma mutation method could be developed as a convenient and effective tool to breed high-yield strains in the fermentation industry, while expanding the plasm application at the same time.

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)

Adaptive mutation: has the unicorn landed?

Science.gov (United States)

Foster, P L

1998-04-01

Reversion of an episomal Lac- allele during lactose selection has been studied as a model for adaptive mutation. Although recent results show that the mutations that arise during selection are not "adaptive" in the original sense, the mutagenic mechanism that produces these mutations may nonetheless be of evolutionary significance. In addition, a transient mutational state induced in a subpopulation of starving cells could provide a species with a mechanism for adaptive evolution.

Adaptive mutation: has the unicorn landed?

Science.gov (United States)

Foster, P L

1998-01-01

Reversion of an episomal Lac- allele during lactose selection has been studied as a model for adaptive mutation. Although recent results show that the mutations that arise during selection are not "adaptive" in the original sense, the mutagenic mechanism that produces these mutations may nonetheless be of evolutionary significance. In addition, a transient mutational state induced in a subpopulation of starving cells could provide a species with a mechanism for adaptive evolution. PMID:9560365

Structural and quantum mechanical computations to elucidate the altered binding mechanism of metal and drug with pyrazinamidase from Mycobacterium tuberculosis due to mutagenicity.

Science.gov (United States)

Rasool, Nouman; Iftikhar, Saima; Amir, Anam; Hussain, Waqar

2018-03-01

Pyrazinamide is known to be the most effective treatment against tuberculosis disease and is known to have bacteriostatic action. By targeting the bacterial spores, this drug reduces the chances for the progression of the infection in organisms. In recent years, increased instances of the drug resistance of bacterial strains are reported. Pyrazinamidase, activator for pyrazinamide, leads to resistance against the drug due to mutagenicity across the world. The present study aimed at the quantum mechanistic analysis of mutations in pyrazinamidase to gain insights into the mechanism of this enzyme. Quantum mechanical calculations were performed to analyse the effect of mutations at the metal coordination site using ORCA software program. Moreover, conformational changes in PZase binding cavity has also been analysed due to mutations of binding pocket residues using CASTp server. In order to elucidate the behaviour of the mutant pyrazinamidase, docking of PZA in the binding pocket of PZase was performed using AutoDock Vina. Analysis of results revealed that iron showed weak binding with the metal coordination site of the mutant proteins due to alteration in electron transfer mechanism. The binding cavity of the mutant PZase has undergone major conformational changes as the volume of pocket increased due to bulky R-chains of mutated amino acids. These conformational changes lead to weak binding of the drug at binding cavity of PZase and reduce the drug activation mechanism leading to increased drug resistance in the bacterial strains. Copyright © 2017 Elsevier Inc. All rights reserved.

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....

The use of a mutationally unstable X-chromosome in Drosophila melanogaster for mutagenicity testing

International Nuclear Information System (INIS)

Rasmuson, B.; Svahlin, H.; Rasmuson, A.; Montell, I.; Olofsson, H.

1978-01-01

Somatic eye-colour mutations in an unstable genetic system, caused by a transposable element in the white locus of the X-chromosome in Drosophila melanogaster, is suggested as an assay system for mutagenicity testing. The system is evaluated by comparison with a corresponding system in a stable X-chromosome. Its sensitivity is confirmed with X-ray and EMS treatment, and it is found to be confined to the specific segment of the X-chromosome where the transposable element is localized. (Auth.)

Assessment of anti-mutagenic effects of stobadine dihydro-chloride on MNNG-induced mutations in Chinese hamster cells V79

International Nuclear Information System (INIS)

Horvathova, E.; Slamenova, D.; Chorvatovicova, D.; Wsolova, L.

1995-01-01

Mutagenicity of N-methyl-n'-nitro-N-nitrosoguanidine (MNNG) and anti-mutagenic effect of antioxidant stobadine (STB) were investigated by so called HGPRT/V79 system. Cells were treated by STB before, during and after MNNG-treatment. Our results showed that the highest anti-mutagenic effect of STB was observed if the drug was given as a pretreatment before exposure of cells to MNNG. This effect was not concentration dependent within the framework of 1.5 - 9 mmol. All other combinations of MNNG- and STB-treatment led to the weaker but statistically significant decrease of 6-TG r mutations. Inhibition of proteosynthesis induced by methylxanthine pentoxifylline in the time of pre-MNNG-treatment removed completely anti-mutagenic effects of STB. In addition of mutagenicity assays, cytotoxicity of STB and combined effects of MNNG and STB were studied. Trypan blue exclusion and growth activity of influenced cells showed that application of STB (1.5 mmol) before or after MNNG (0.5 μg/cm 3 ) treatment had a similar toxic effects as MNNG alone. Application of STB during MNNG-treatment or pretreatment of cells with STB followed by combined treatment of cells by STB + MNNG statistically significantly decreased viability of cells. There are probably no relationship between the anti-mutagenic and the toxic effects of combined influence of STB and MNNG on V79 cells. (author)

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.)

Studies on mutation techniques in rice breeding

International Nuclear Information System (INIS)

Wang Cailian; Chen Qiufang; Jin Wei

2001-01-01

Synthetical techniques for improving rice mutation breeding efficiency were studied. The techniques consist of corresponding relationship between radiosensitivity and mutation frequency, choosing appropriate materials, combination of physical and chemical mutagens, mutagenic effects of the new mutagenic agents as proton, ions, synchronous irradiation and space mutation. These techniques and methods for inducing mutations are very valuable to increase inducing mutation efficiency and breeding level

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

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)

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

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.)

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

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

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 ...

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 ...

Mutational specificity of SOS mutagenesis

International Nuclear Information System (INIS)

Kato, Takeshi

1986-01-01

In an approach to the isolation of mutants of E. coli unable to produce mutations by ultraviolet light, the author has found new umuC-mutants. Their properties could be explained by ''SOS hypothesis of Radman and Witkin'', which has now been justified by many investigators. Analysis of the umuC region of E. coli chromosome cloned in pSK 100 has led to the conclusion that two genes, umuD and umuC, having the capacity of mutation induction express in the same mechanism as that of SOS genes, which is known to be inhibited by LexA protein bonding to ''SOS box'' found at promotor region. Suppressor analysis for mutational specificity has revealed: (i) umuDC-independent mutagens, such as EMS and (oh) 4 Cy, induce selected base substitution alone; and (ii) umuDC-dependent mutagens, such as X-rays and gamma-rays, induce various types of base substitution simultaneously, although they have mutational specificity. In the umuDC-dependent processes of basechange mutagenesis, the spectra of base substitution were a mixture of base substitution reflecting the specific base damages induced by individual mutagens and nonspecific base substitution. In conclusion, base substitution plays the most important role in umuDC-dependent mutagenesis, although mutagenesis of umuDC proteins remains uncertain. (Namekawa, K.)

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.

Atypical Role for PhoU in Mutagenic Break Repair under Stress in Escherichia coli.

Directory of Open Access Journals (Sweden)

Janet L Gibson

Full Text Available Mechanisms of mutagenesis activated by stress responses drive pathogen/host adaptation, antibiotic and anti-fungal-drug resistance, and perhaps much of evolution generally. In Escherichia coli, repair of double-strand breaks (DSBs by homologous recombination is high fidelity in unstressed cells, but switches to a mutagenic mode using error-prone DNA polymerases when the both the SOS and general (σS stress responses are activated. Additionally, the σE response promotes spontaneous DNA breakage that leads to mutagenic break repair (MBR. We identified the regulatory protein PhoU in a genetic screen for functions required for MBR. PhoU negatively regulates the phosphate-transport and utilization (Pho regulon when phosphate is in excess, including the PstB and PstC subunits of the phosphate-specific ABC transporter PstSCAB. Here, we characterize the PhoU mutation-promoting role. First, some mutations that affect phosphate transport and Pho transcriptional regulation decrease mutagenesis. Second, the mutagenesis and regulon-expression phenotypes do not correspond, revealing an apparent new function(s for PhoU. Third, the PhoU mutagenic role is not via activation of the σS, SOS or σE responses, because mutations (or DSBs that restore mutagenesis to cells defective in these stress responses do not restore mutagenesis to phoU cells. Fourth, the mutagenesis defect in phoU-mutant cells is partially restored by deletion of arcA, a gene normally repressed by PhoU, implying that a gene(s repressed by ArcA promotes mutagenic break repair. The data show a new role for PhoU in regulation, and a new regulatory branch of the stress-response signaling web that activates mutagenic break repair in E. coli.

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

Mutation induction in Haemophilus influenzae by ICR-191. Pt. 1

International Nuclear Information System (INIS)

Perdue, S.W.; Kimball, R.F.; McGray, P.C.; Tennessee Univ., Oak Ridge

1981-01-01

The investigation of mutagenic mechanisms in Haemophilus influenzae has been confined until now to mutagens that normally produce mainly base pair substitutions. This paper describes the development of a system suitable for detecting frameshift mutations induced by ICR-191. The system involves reversions from thymidine dependence to thymidine independence. Evidence is presented from a comparison of the responses to ICR-191 and to N-methyl-N'-nitro-N-nitrosoguanidine that the system is specific for frameshift mutations. The genetic recombination involved in transformation leads to a marked increase in spontaneous reversion of the frameshift mutations but not of the base substitution mutations. Presumably, this is a consequence of mispairing, with consequent change in the number of bases, during the recombination. (orig.)

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.)

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

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).

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.

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...

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.)

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.

Chloroplast mutations induced by 9-aminoacridine hydrochloride are independent of the plastome mutator in Oenothera.

Science.gov (United States)

GuhaMajumdar, M; Baldwin, S; Sears, B B

2004-02-01

Oenothera plants homozygous for the recessive plastome mutator allele ( pm) show chloroplast DNA (cpDNA) mutation frequencies that are about 1,000-fold higher than spontaneous levels. The pm-encoded gene product has been hypothesized to have a function in cpDNA replication, repair and/or mutation avoidance. Previous chemical mutagenesis experiments with the alkylating agent nitroso-methyl urea (NMU) showed a synergistic effect of NMU on the induction of mutations in the pm line, suggesting an interaction between the pm-encoded gene product and one of the repair systems that corrects alkylation damage. The goal of the experiments described here was to examine whether the pm activity extends to the repair of damage caused by non-alkylating mutagens. To this end, the intercalating mutagen, 9-aminoacridine hydrochloride (9AA) was tested for synergism with the plastome mutator. A statistical analysis of the data reported here indicates that the pm-encoded gene product is not involved in the repair of the 9AA-induced mutations. However, the recovery of chlorotic sectors in plants derived from the mutagenized seeds shows that 9AA can act as a mutagen of the chloroplast genome.

Mutation direction by irradiation in rice

International Nuclear Information System (INIS)

Wang Cailian; Chen Qiufang; Jin Wei; Lu Yimei

2001-01-01

The mutation directions of rice were studied. The results indicated that the mutation directions of rice induced by 14 C were invert correlation to their genetic backgrounds of tested rice varieties, i.e. early mature and short stem varieties produced later mature and higher stem mutation; late mature and high stem varieties produced earlier mature and shorter stem mutation; the varieties of middle maturity and height produced both direction mutations of earlier and later maturity or shorter and higher stem. The mutation directions induced by 14 C were also related to treated doses and stages. Frequency of earlier maturity mutation by protons treatment were higher than those induced by other mutagens. Frequency of later maturity by γ-rays were higher than those induced by other mutagens. Frequency of short stem mutation by synchronous irradiation (soft X-rays) were higher than those induced by other mutagens. Frequency of beneficial mutation induced by proton treatment were higher than those induced by γ-rays

Comparative effects of ionizing radiation and two gaseous chemical mutagens on somatic mutation induction in one mutable and two non-mutable clones of Tradescantia

International Nuclear Information System (INIS)

Nauman, C.H.; Sparrow, A.H.; Schairer, L.A.

1976-01-01

The X-ray dose responses of mutable clone 0106 of Tradescantia (mutable for blue to pink), and its parent clone 02 have been determined for pink and colorless mutations in stamen hair cells, and are compared to the previously determined X-ray response for pink mutations of a third unrelated clone, clone 4430 (hybrid of T. subacaulis and T. hirsutiflora). X-ray response curves are compared to the response curves of the same three clones after exposure to the gaseous phase of the alkylating agent ethyl methanesulfate (EMS) and the fumigant and gasoline additive 1,2-dibromoethane (DBE). X-irradiation induces a pink mutation rate in mutable clone 0106 that is significantly higher than that of the nearly identical pink mutation rates in clones 02 and 4430. However, the colorless mutation rates of clones 02 and 0106 are not significantly different from one another. In clones 02 and 0106, pink mutations occur more frequently than colorless mutations at lower doses, but colorless dose-response curves saturate at higher doses than do those for pink mutations. Exposure-response curves for EMS and DBE have characteristics similar to those of X-ray response curves: exponential rise followed by an area of saturation. However, it was found that the relative sensitivities of the three clones to the gaseous mutagens and to ionizing radiation do not parallel one another. Where clones 02 and 4430 are equally sensitive to X-rays, at equal mutagen concentration clone 4430 is 6-7 times more sensitive to EMS and 7-9 times more sensitive to DBE than is clone 02. Mutable clone 0106 shows intermediate sensitivities to both EMS and DBE

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)

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.)

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.

Analysis of 6174delT Mutation in BRCA2 Gene by Mutagenically Separated PCR Among Libyan Patients with Breast Cancer

Directory of Open Access Journals (Sweden)

Lamia Elfandi

2016-03-01

Full Text Available Background: Breast cancer is the most common malignancy among women. It is estimated that 1 in 10 women worldwide is affected by breast cancer during their lifetime. In 5 to 10% of breast cancer patients, the disease results from a hereditary predisposition, which can be attributable to mutations in either of two tumor suppressor genes, BRCA1 and BRCA2 to a large extent. BRCA2 6174delT mutation constitutes the common mutant alleles which predispose to hereditary breast cancer in the Ashkenazi population with a reported carrier frequency of 1.52%. In this study, we investigated the presence of the 6174delT mutation of the BRCA2 gene in Libyan woman affected with breast cancer and compared the results with those of other population groups.Methods: Eighty- five Libyan women with breast cancer in additions to 5 relatives of the patients (healthy individuals were recruited to this study. We obtained clinical information, family history, and peripheral blood for DNA extraction and analyzed the data using multiplex mutagenic polymerase chain reaction (MS-PCR for detection of 6174delT mutation in the BRCA2 gene. Results: The 6174delT of the BRCA2 gene was not detected either in the 85 patients with breast cancer (18 with familial breast cancer and 67 with sporadic breast cancer nor in the 5 healthy individuals. Conclusions: The present study showed that the 6174delT of the BRCA2 gene was not detectable using mutagenic PCR in the Libyan patients with breast cancer and can be considered to be exceedingly rare

Manual on mutation breeding. 2. ed.

International Nuclear Information System (INIS)

1977-01-01

The manual is a compilation of work done on the use of induced mutations in plant breeding, and presents general methods and techniques in this field. The use of chemical mutagens and ionizing radiations (X-rays, gamma rays, α- and β-particles, protons, neutrons) are described as well as the effects of these mutagens. The different types of mutations achieved can be divided into genome mutations, chromosome mutations and extra nuclear mutations. Separate chapters deal with mutation techniques in breeding seed-propagated species and asexually propagated plants (examples of development of cultivars given). Plant characters which can be improved by mutation breeding include yield, ripening time, growth habit, disease resistance and tolerance to environmental factors (temperature, salinity etc.). The use of mutagens for some specific plant breeding problems is discussed and attention is also paid to somatic cell genetics in connection with induced mutations. The manual contains a comprehensive bibliography (60 p. references) and a subject index

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.

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

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.

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).

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)

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.

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.

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.)

Experimental mutations in soybean and their selection value

International Nuclear Information System (INIS)

Sichkar', V.I.

1979-01-01

Efficiency of widely used chemical mutagens and gamma irradiation in inducing chlorophyll changes in some soya varieties has been compared in order to further specify the relationship between this type of mutations and other morphological changes. The most active mutations found were NMU, NEU, EI and gamma radiation. The frequency of chrolophyll changes depended on the mutagen concentration and soya variety and varied from 1.58% to 19.04%. EO, NDMM and DMS produced 4-5 times lower yield of chlorophyll mutations. The following mutagen concentrations for the varieties studied were found optimum (in per cent): NMU - 0.0125, NEU - 0.025, EI - 0.03, EO - 0.05, NDMM - 0.0O625, DMS - 0.02. No relationship between the dose of gamma radiation and the mutation frequency was found. Varieties of VNIIMK 9186 and Lanka were the most mutable, 89-10 hybrid showed very low mutability. Mutagens that induced high frequency of mutations also gave the broadest spectrum of changes. Most frequent changes were xantha, lutescens and xanthaterminalis. Very few mutations from green color to white one were isolated

Tautomerism provides a molecular explanation for the mutagenic properties of the anti-HIV nucleoside 5-aza-5,6-dihydro-2'-deoxycytidine.

Science.gov (United States)

Li, Deyu; Fedeles, Bogdan I; Singh, Vipender; Peng, Chunte Sam; Silvestre, Katherine J; Simi, Allison K; Simpson, Jeffrey H; Tokmakoff, Andrei; Essigmann, John M

2014-08-12

Viral lethal mutagenesis is a strategy whereby the innate immune system or mutagenic pool nucleotides increase the error rate of viral replication above the error catastrophe limit. Lethal mutagenesis has been proposed as a mechanism for several antiviral compounds, including the drug candidate 5-aza-5,6-dihydro-2'-deoxycytidine (KP1212), which causes A-to-G and G-to-A mutations in the HIV genome, both in tissue culture and in HIV positive patients undergoing KP1212 monotherapy. This work explored the molecular mechanism(s) underlying the mutagenicity of KP1212, and specifically whether tautomerism, a previously proposed hypothesis, could explain the biological consequences of this nucleoside analog. Establishing tautomerism of nucleic acid bases under physiological conditions has been challenging because of the lack of sensitive methods. This study investigated tautomerism using an array of spectroscopic, theoretical, and chemical biology approaches. Variable temperature NMR and 2D infrared spectroscopic methods demonstrated that KP1212 existed as a broad ensemble of interconverting tautomers, among which enolic forms dominated. The mutagenic properties of KP1212 were determined empirically by in vitro and in vivo replication of a single-stranded vector containing a single KP1212. It was found that KP1212 paired with both A (10%) and G (90%), which is in accord with clinical observations. Moreover, this mutation frequency is sufficient for pushing a viral population over its error catastrophe limit, as observed before in cell culture studies. Finally, a model is proposed that correlates the mutagenicity of KP1212 with its tautomeric distribution in solution.

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.

Synergistic interaction of gamma rays and some metallic salts in the induction of chlorophyll mutations in rice

International Nuclear Information System (INIS)

Reddy, T.P.; Vaidyanath, K.

1978-01-01

In this study the mutagenic activity of 9 metallic salts was tested in comparison and conjunction with gamma rays on rice seed. In M 2 , barium and cadmium produced chlorophyll mutation and mutant frequencies on a par with those of 20 kR gamma rays. Similarly, copper and mercury induced moderately high mutation and mutant frequencies. Salts of strontium, iron and lead showed rather weak mutagenic effects. On the other hand, two metals - manganese anc calcium - failed to provoke chlorophyll mutations in rice seed. Sequential treatments of gamma rays + 5 metals, namely Sr, Cd, Hg, Pb and Cu, produced synergistic yields of chlorophyll mutants in the M 2 generation. Two genetically active metals, Ba and Fe, showed less than additive effects when post-treated after gamma irradiation. Manganese, which failed to induce chlorophyll mutations in independent treatment, potentiated the mutagenic activity of gamma radiation in sequential treatment. On the other hand, sequential treatment with calcium seemed to confer a substantial protection against gamma-ray-induced genetic lesions. The probable mechanisms of synergistic interaction, mutagenic potentiation and protection, observed in sequential treatments, are discussed. (Auth.)

Induced mutations in chickpea (Cicer arietinum L.) II. frequency and spectrum of chlorophyll mutations

International Nuclear Information System (INIS)

Kharkwal, M.C.

1998-01-01

A comparative study of frequency and spectrum of chlorophyll mutations induced by two physical (gamma rays, fast neutrons) and two chemical mutagens (NMU, EMS) in relation to the effects in M1 plants and induction of mutations in M2 was made in four chickpea (Cicer arietinum L.) varieties, two desi (G 130 & H 214) one Kabuli (C 104) and one green seeded (L 345). The treatments included three doses each of gamma rays (400, 500 & 600 Gy) and fast neutrons (5, 10 & 15 Gy) and two concentrations with two different durations of two chemical mutagens, NMU [0.01% (20h), & 0.02% (8h)] and EMS [0.1% (20h) & 0.2% (8h)]. The frequencies and spectrum of three different kinds of induced chlorophyll mutations in the order albina (43.5%), chlorina (27.3%) and xantha (24.2%) were recorded. Chemical mutagens were found to be efficient in inducing chlorophyll mutations in chickpea. Highest frequency of mutations was observed in green seeded var. L 345 (83% of M1 families and 19.9/1000 M2 plants). Kabuli var. C 104 was least responsive for chlorophyll mutations

Mutagenic Effects of Ribavirin on Hepatitis E Virus—Viral Extinction versus Selection of Fitness-Enhancing Mutations

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Daniel Todt

2016-10-01

Full Text Available Hepatitis E virus (HEV, an important agent of viral hepatitis worldwide, can cause severe courses of infection in pregnant women and immunosuppressed patients. To date, HEV infections can only be treated with ribavirin (RBV. Major drawbacks of this therapy are that RBV is not approved for administration to pregnant women and that the virus can acquire mutations, which render the intra-host population less sensitive or even resistant to RBV. One of the proposed modes of action of RBV is a direct mutagenic effect on viral genomes, inducing mismatches and subsequent nucleotide substitutions. These transition events can drive the already error-prone viral replication beyond an error threshold, causing viral population extinction. In contrast, the expanded heterogeneous viral population can facilitate selection of mutant viruses with enhanced replication fitness. Emergence of these mutant viruses can lead to therapeutic failure. Consequently, the onset of RBV treatment in chronically HEV-infected individuals can result in two divergent outcomes: viral extinction versus selection of fitness-enhanced viruses. Following an overview of RNA viruses treated with RBV in clinics and a summary of the different antiviral modes of action of this drug, we focus on the mutagenic effect of RBV on HEV intrahost populations, and how HEV is able to overcome lethal mutagenesis.

Mutagenic Effects of Ribavirin on Hepatitis E Virus-Viral Extinction versus Selection of Fitness-Enhancing Mutations.

Science.gov (United States)

Todt, Daniel; Walter, Stephanie; Brown, Richard J P; Steinmann, Eike

2016-10-13

Hepatitis E virus (HEV), an important agent of viral hepatitis worldwide, can cause severe courses of infection in pregnant women and immunosuppressed patients. To date, HEV infections can only be treated with ribavirin (RBV). Major drawbacks of this therapy are that RBV is not approved for administration to pregnant women and that the virus can acquire mutations, which render the intra-host population less sensitive or even resistant to RBV. One of the proposed modes of action of RBV is a direct mutagenic effect on viral genomes, inducing mismatches and subsequent nucleotide substitutions. These transition events can drive the already error-prone viral replication beyond an error threshold, causing viral population extinction. In contrast, the expanded heterogeneous viral population can facilitate selection of mutant viruses with enhanced replication fitness. Emergence of these mutant viruses can lead to therapeutic failure. Consequently, the onset of RBV treatment in chronically HEV-infected individuals can result in two divergent outcomes: viral extinction versus selection of fitness-enhanced viruses. Following an overview of RNA viruses treated with RBV in clinics and a summary of the different antiviral modes of action of this drug, we focus on the mutagenic effect of RBV on HEV intrahost populations, and how HEV is able to overcome lethal mutagenesis.

Tautomerism provides a molecular explanation for the mutagenic properties of the anti-HIV nucleoside 5-aza-5,6-dihydro-2′-deoxycytidine

Science.gov (United States)

Li, Deyu; Fedeles, Bogdan I.; Singh, Vipender; Peng, Chunte Sam; Silvestre, Katherine J.; Simi, Allison K.; Simpson, Jeffrey H.; Tokmakoff, Andrei; Essigmann, John M.

2014-01-01

Viral lethal mutagenesis is a strategy whereby the innate immune system or mutagenic pool nucleotides increase the error rate of viral replication above the error catastrophe limit. Lethal mutagenesis has been proposed as a mechanism for several antiviral compounds, including the drug candidate 5-aza-5,6-dihydro-2′-deoxycytidine (KP1212), which causes A-to-G and G-to-A mutations in the HIV genome, both in tissue culture and in HIV positive patients undergoing KP1212 monotherapy. This work explored the molecular mechanism(s) underlying the mutagenicity of KP1212, and specifically whether tautomerism, a previously proposed hypothesis, could explain the biological consequences of this nucleoside analog. Establishing tautomerism of nucleic acid bases under physiological conditions has been challenging because of the lack of sensitive methods. This study investigated tautomerism using an array of spectroscopic, theoretical, and chemical biology approaches. Variable temperature NMR and 2D infrared spectroscopic methods demonstrated that KP1212 existed as a broad ensemble of interconverting tautomers, among which enolic forms dominated. The mutagenic properties of KP1212 were determined empirically by in vitro and in vivo replication of a single-stranded vector containing a single KP1212. It was found that KP1212 paired with both A (10%) and G (90%), which is in accord with clinical observations. Moreover, this mutation frequency is sufficient for pushing a viral population over its error catastrophe limit, as observed before in cell culture studies. Finally, a model is proposed that correlates the mutagenicity of KP1212 with its tautomeric distribution in solution. PMID:25071207

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)

Enhanced mutagenicity of low doses of alkylating agents and UV-light by inhibition of ribonucleotide reductase

International Nuclear Information System (INIS)

Jenssen, D.

1986-01-01

Monofunctional alkylating agents and UV-light are potent inducers of gene mutations in mammalian cells. Most data on these agent are supporting the idea that 0/sup 6/-alkylguanine is the dominating lesion responsible for the mutations induced by the alkylating agents and thymine-dimers in the case of UV-light. However, little is known about the mutagenic fate of these lesions during the replicative process. This is an essential issue to investigate not the least because of quantitative aspects. By investigating the factors affecting the mutagenic yield of these lesions, they hope to get further information on the mechanisms(s) involved. To study this, a system was applied which involves synchronized V79 Chinese hamster cells and inhibitors of the replication process. By applying hydroxyurea (HU), as inhibitor of the ribonucleotide reductase (RNR) step in DNA synthesis, the effect of nucleotide pool imbalance has been studied at the HGPRT-locus using V79 Chinese hamster cells

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

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

Induction and isolation of somatic mutations in vegetatively propagated plants

International Nuclear Information System (INIS)

Donini, B.

1975-01-01

Research carried out since 1963 concentrated on techniques of mutagenic treatment: problems of exposure, type of radiation (acute irradiation by x- and γ-rays, and chronic exposure in the gamma field), conditions during and after irradiation, mechanisms of mutation induction, and methodology of isolation of somatic mutations. Analyses of somatic mutations included studies on apple, pear, olive, peach, grape and cherry plants. Young trees, dormant and rooted scions, summer and floral buds or seeds were used

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)

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.

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.

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.)

Prospects for cellular mutational assays in human populations

International Nuclear Information System (INIS)

Mendelsohn, M.L.

1984-01-01

Practical, sensitive, and effective human cellular assays for detecting somatic and germinal mutations would have great value in environmental mutagenesis and carcinogenesis studies. Such assays would fill the void between human mutagenicity and the data that exist from short-term tests and from mutagenicity in other species. This paper discusses the following possible human cellular assays: (1) HPRT (hypoxanthine phosphoribosyltransferase) somatic cell mutation based on 6-thioguanine resistance; (2) hemoglobin somatic cell mutation assay; (3) glycophorin somatic cell mutation assay; and (4) LDH-X sperm cell mutation assay. 18 references

Prospects for cellular mutational assays in human populations

Energy Technology Data Exchange (ETDEWEB)

Mendelsohn, M.L.

1984-06-29

Practical, sensitive, and effective human cellular assays for detecting somatic and germinal mutations would have great value in environmental mutagenesis and carcinogenesis studies. Such assays would fill the void between human mutagenicity and the data that exist from short-term tests and from mutagenicity in other species. This paper discusses the following possible human cellular assays: (1) HPRT (hypoxanthine phosphoribosyltransferase) somatic cell mutation based on 6-thioguanine resistance; (2) hemoglobin somatic cell mutation assay; (3) glycophorin somatic cell mutation assay; and (4) LDH-X sperm cell mutation assay. 18 references.

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)

Molecular Mechanisms for High Hydrostatic Pressure-Induced Wing Mutagenesis in Drosophila melanogaster.

Science.gov (United States)

Wang, Hua; Wang, Kai; Xiao, Guanjun; Ma, Junfeng; Wang, Bingying; Shen, Sile; Fu, Xueqi; Zou, Guangtian; Zou, Bo

2015-10-08

Although High hydrostatic pressure (HHP) as an important physical and chemical tool has been increasingly applied to research of organism, the response mechanisms of organism to HHP have not been elucidated clearly thus far. To identify mutagenic mechanisms of HHP on organisms, here, we treated Drosophila melanogaster (D. melanogaster) eggs with HHP. Approximately 75% of the surviving flies showed significant morphological abnormalities from the egg to the adult stages compared with control flies (p melanogaster induced by HHP were used to investigate the mutagenic mechanisms of HHP on organism. Thus 285 differentially expressed genes associated with wing mutations were identified using Affymetrix Drosophila Genome Array 2.0 and verified with RT-PCR. We also compared wing development-related central genes in the mutant flies with control flies using DNA sequencing to show two point mutations in the vestigial (vg) gene. This study revealed the mutagenic mechanisms of HHP-induced mutagenesis in D. melanogaster and provided a new model for the study of evolution on organisms.

Tautomerism provides a molecular explanation for the mutagenic properties of the anti-HIV nucleoside 5-aza-5,6-dihydro-2′-deoxycytidine

OpenAIRE

Li, Deyu; Fedeles, Bogdan I.; Singh, Vipender; Peng, Chunte Sam; Silvestre, Katherine J.; Simi, Allison K.; Simpson, Jeffrey H.; Tokmakoff, Andrei; Essigmann, John M.

2014-01-01

Unlike conventional antiviral therapy, lethal mutagenesis is a therapeutic strategy that exploits the high mutation rates of certain viruses. It works by intentionally increasing the viral mutation rate, causing excessive error accumulation and viral population collapse. The mutagenic nucleoside analog 5-aza-5,6-dihydro-2′-deoxycytidine (KP1212) is specifically designed to use lethal mutagenesis against HIV. The mechanism of KP1212 mutagenesis was proposed to involve tautomerism—the repositio...

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

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 mutagenictity 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. 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 (50μg/ml) and quinacrine dihydrochloride (25 μg/ml). All drugs tested give synergistic effets 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.)

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 mutagenictity 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. 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) 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.

Two-dimensional IR spectroscopy of the anti-HIV agent KP1212 reveals protonated and neutral tautomers that influence pH-dependent mutagenicity.

Science.gov (United States)

Peng, Chunte Sam; Fedeles, Bogdan I; Singh, Vipender; Li, Deyu; Amariuta, Tiffany; Essigmann, John M; Tokmakoff, Andrei

2015-03-17

Antiviral drugs designed to accelerate viral mutation rates can drive a viral population to extinction in a process called lethal mutagenesis. One such molecule is 5,6-dihydro-5-aza-2'-deoxycytidine (KP1212), a selective mutagen that induces A-to-G and G-to-A mutations in the genome of replicating HIV. The mutagenic property of KP1212 was hypothesized to originate from its amino-imino tautomerism, which would explain its ability to base pair with either G or A. To test the multiple tautomer hypothesis, we used 2D IR spectroscopy, which offers subpicosecond time resolution and structural sensitivity to distinguish among rapidly interconverting tautomers. We identified several KP1212 tautomers and found that >60% of neutral KP1212 is present in the enol-imino form. The abundant proportion of this traditionally rare tautomer offers a compelling structure-based mechanism for pairing with adenine. Additionally, the pKa of KP1212 was measured to be 7.0, meaning a substantial population of KP1212 is protonated at physiological pH. Furthermore, the mutagenicity of KP1212 was found to increase dramatically at pH KP1212 molecules. Overall, our data reveal that the bimodal mutagenic properties of KP1212 result from its unique shape shifting ability that utilizes both tautomerization and protonation.

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

The mutagenicity of indoor air particles in a residential pilot field study: Application and evaluation of new methodologies

Science.gov (United States)

Lewtas, Joellen; Goto, Sumio; Williams, Katherine; Chuang, Jane C.; Petersen, Bruce A.; Wilson, Nancy K.

The mutagenicity of indoor air paniculate matter has been measured in a pilot field study of homes in Columbus, Ohio during the 1984 winter. The study was conducted in eight all natural-gas homes and two all electric homes. Paniculate matter and semi-volatile organic compounds were collected indoors using a medium volume sampler. A micro-forward mutation bioassay employing Salmonella typhimurium strain TM 677 was used to quantify the mutagenicity in solvent extracts of microgram quantities of indoor air particles. The mutagenicity was quantified in terms of both mutation frequency per mg of organic matter extracted and per cubic meter of air sampled. The combustion source variables explored in this study included woodburning in fireplaces and cigarette smoking. Homes in which cigarette smoking occurred had the highest concentrations of mutagenicity per cubic meter of air. The average indoor air mutagenicity per cubic meter was highly correlated with the number of cigarettes smoked. When the separate sampling periods in each room were compared, the mutagenicity in the kitchen samples was the most highly correlated with the number of cigarettes smoked.

Proceedings of the 8th workshop on plant mutation breeding. Effective use of physical/chemical mutagens

Energy Technology Data Exchange (ETDEWEB)

Kume, Tamikazu; Watanabe, Kazuo; Tano, Shigemitsu (eds.) [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

2001-03-01

The Workshop on Plant Mutation Breeding of FNCA (Forum for Nuclear Cooperation in Asia), was held on 9-13 October 2000 in Hanoi, Vietnam. The Workshop was co-sponsored by the Science and Technology Agency (STA), the Ministry of Science, Technology and Environment (MOSTE of Vietnam) and the Ministry of Agriculture and Rural Development (MARD of Vietnam) in cooperation with the Ministry of Agriculture, Forestry and Fisheries (MAFF), National Institute of Agrobiological Resources (NIAR of Vietnam), the Japan Atomic Industrial Forum (JAIF) and Japan Atomic Energy Research Institute (JAERI). Two Scientists, a Project Leader and an expert on methodology for plant/crop mutation breeding, participated from each of the member countries, i.e. China, Indonesia, Malaysia, the Philippines, Thailand, Vietnam and Japan. Also attending the Workshop were, one participant from Korea, seven participants from both Japan and Vietnam. The number of the participants in the Workshop totalled about sixty people including guests and observers. Sixteen papers including eight invited papers on the current status of methodology for plant/crop mutation breeding in the participating countries were presented. Discussions were focused on the subject concerning 'Effective Use of Physical/Chemical Mutagens', as well as a detailed report on the current status of research in each participating country. In addition, the topics of developing a mutant breeding database, an information exchange for plant/crop mutation breeding, and more tightly bound international co-operative research in the near future were also high on the agenda. This proceeding compiles the invited and contributed papers that were submitted from the speakers. (author)

Proceedings of the 8th workshop on plant mutation breeding. Effective use of physical/chemical mutagens

Energy Technology Data Exchange (ETDEWEB)

Kume, Tamikazu; Watanabe, Kazuo; Tano, Shigemitsu [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

2001-03-01

The Workshop on Plant Mutation Breeding of FNCA (Forum for Nuclear Cooperation in Asia), was held on 9-13 October 2000 in Hanoi, Vietnam. The Workshop was co-sponsored by the Science and Technology Agency (STA), the Ministry of Science, Technology and Environment (MOSTE of Vietnam) and the Ministry of Agriculture and Rural Development (MARD of Vietnam) in cooperation with the Ministry of Agriculture, Forestry and Fisheries (MAFF), National Institute of Agrobiological Resources (NIAR of Vietnam), the Japan Atomic Industrial Forum (JAIF) and Japan Atomic Energy Research Institute (JAERI). Two Scientists, a Project Leader and an expert on methodology for plant/crop mutation breeding, participated from each of the member countries, i.e. China, Indonesia, Malaysia, the Philippines, Thailand, Vietnam and Japan. Also attending the Workshop were, one participant from Korea, seven participants from both Japan and Vietnam. The number of the participants in the Workshop totalled about sixty people including guests and observers. Sixteen papers including eight invited papers on the current status of methodology for plant/crop mutation breeding in the participating countries were presented. Discussions were focused on the subject concerning 'Effective Use of Physical/Chemical Mutagens', as well as a detailed report on the current status of research in each participating country. In addition, the topics of developing a mutant breeding database, an information exchange for plant/crop mutation breeding, and more tightly bound international co-operative research in the near future were also high on the agenda. This proceeding compiles the invited and contributed papers that were submitted from the speakers. (author)

Radiation-induced mutagenicity in repair deficient Chinese hamster ovary (CHO) mutants

International Nuclear Information System (INIS)

Tesmer, J.G.; Saunders, E.H.; Chen, D.J.

1987-01-01

To determine if there is a relationship between DNA double-strand break repair and mutagenicity the authors utilized two x-ray sensitive mutants of Chinese hamster ovary cells along with the parental line K1. The two mutant lines xrs-5 and xrs-6, which have different DSB repair capabilities, were used to determine cell killing and 6-thioguanine resistance (6TG/sup r/) mutation frequencies induced by either x-rays of α-particles, x-ray survival data indicated the two mutant lines have similar sensitivity and are 5-7 fold more sensitive than the parental line K1. The mutant lines are also sensitive to α-particles but to a lesser extent. The authors' 6TG mutation data indicated that the two mutant lines are hypermutable. When mutation frequencies were plotted against the log of survival, mutation frequency at a given survival level was greater in mutant cell population than in parental K1 cells. Their results support the notion that repair of DSB play an important role in the expression of radiation-induced cell killing and mutagenicity

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

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

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.

Molecular mechanisms of mutagenesis determined by the recombinant DNA technology

International Nuclear Information System (INIS)

Lee, W.R.

1985-01-01

A study of the alteration of the DNA in the mutant gene can determine mechanisms of mutation by distinguishing between mutations induced by transition, transversion, frameshifts of a single base and deletions involving many base pairs. The association of a specific pattern of response with a mutagen will permit detecting mutants induced by the mutagen with a reduced background by removing mutations induced by other mechanisms from the pool of potential mutants. From analyses of studies that have been conducted, it is quite apparent that there are substantial differences among mutagens in their modes of action. Of 31 x-ray induced mutants, 20 were large deletions while only 3 showed normal Southern blots. Only one mutant produced a sub-unit polypeptide of normal molecular weight and charge in the in vivo test whereas in vitro synthesis produced a second one. In contrast, nine of thirteen EMS induced mutants produced cross-reacting proteins with sub-unit polypeptide molecular weights equivalent to wild type. Two of three ENU induced mutants recently analyzed in our laboratory produced protein with sub-unit polypeptide molecular weight and electrical charge similar to the wild type stock in which the mutants were induced. One ENU induced mutation is a large deletion. 21 refs., 1 fig

Influence of single and combination treatments of physical and chemical mutagen on chlorophyll mutations in Finger Millet

International Nuclear Information System (INIS)

Kumar, Binod; Mahto, Jaylal; Haider, Z.A.

1993-01-01

Gamma rays, ethyl methane sulfonate (EMS) and their combined treatments influenced differently in producing chlorophyll mutations. A good number of chlorophyll mutants with varied frequencies were recorded in M 2 generation. The frequency of chlorophyll mutants was higher at lower doses of gamma rays, EMS and their combination treatments. The most frequently observed mutant was Albino type. The other chlorophyll mutants isolated were Xantha, Viridis, Striata and Tigrina. The frequency of tigrina and striata was lowest in variety A-404 and Hr-374, respectively. The efficiency and effectiveness was high at the lower doses of mutagens in both the varieties. EMS (0.2%) was more effective than the corresponding lower dose of gamma rays for both the varieties. (author). 10 refs., 4 tabs

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.)

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)

Analysis of mutagenic DNA repair in a thermoconditional mutant of Saccharomyces cerevisiae. Pt. 3

International Nuclear Information System (INIS)

Siede, W.; Eckardt, F.

1986-01-01

Recent studies regarding the influence of cycloheximide on the temperature-dependent increase in survival and mutation frequencies of a thermoconditional rev2 mutant lead to the suggestion that the REV2-coded mutagenic repair function is UV-inducible. In the present study we show that stationary-phase rev2sup(ts) cells are characterized by a biphasic linear-quadratic dose-dependence of mutation induction ('mutation kinetics') of ochre alleles at 23 0 C (permissive temperature) but linear kinetics at the restrictive temperature of 36 0 C. Mathematical analysis using a model based on Poisson statistics and a further mathematical procedure, the calculation of 'apparent survival', support the assumption kinetics investigated can be attributed to a UV-inducible component of mutagenic DNA repair controlled by the REV2 gene. (orig.)

[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.

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

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)

Molecular analysis of formaldehyde-induced mutations in human lymphoblasts and E. coli

International Nuclear Information System (INIS)

Crosby, R.M.; Richardson, K.K.; Craft, T.R.; Benforado, K.B.; Liber, H.L.; Skopek, T.R.

1988-01-01

The molecular nature of formaldehyde (HCHO)-induced mutations was studied in both human lymphoblasts and E. coli. Thirty HPRT - human lymphoblast colonies induced by eight repetitive 150 μM HCHO treatments were characterized by Southern blot analysis. Fourteen of these mutants (47%) had visible deletions of some or all of the X-linked HPRT bands, indicating that HCHO can induce large losses of DNA in human lymphoblasts. In E. coli., DNA alterations induced by HCHO were characterized with use of the xanthine guanine phosphoribosyl transferase (gpt) gene as the genetic target. Exposure of E. coli to 4 mM HCHO for 1 hr induced large insertions (41%), large deletions (18%), and point mutations (41%). Dideoxy DNA sequencing revealed that most of the point mutations were transversions at GC base pairs. In contrast, exposure of E. coli to 40 mM HCHO for 1 hr produced 92% point mutations, 62% of which were transitions at a single AT base pair in the gene. Therefore, HCHO is capable of producing different genetic alterations in E. coli at different concentrations, suggesting fundamental differences in the mutagenic mechanisms operating at the two concentrations used. Naked pSV2gpt plasmid DNA was exposed to 3.3 or 10 mM HCHO and transformed into E. coli. Most of the resulting mutations were frameshifts, again suggesting a different mutagenic mechanism

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

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

A multi-step process of viral adaptation to a mutagenic nucleoside analogue by modulation of transition types leads to extinction-escape.

Directory of Open Access Journals (Sweden)

Rubén Agudo

2010-08-01

Full Text Available Resistance of viruses to mutagenic agents is an important problem for the development of lethal mutagenesis as an antiviral strategy. Previous studies with RNA viruses have documented that resistance to the mutagenic nucleoside analogue ribavirin (1-β-D-ribofuranosyl-1-H-1,2,4-triazole-3-carboxamide is mediated by amino acid substitutions in the viral polymerase that either increase the general template copying fidelity of the enzyme or decrease the incorporation of ribavirin into RNA. Here we describe experiments that show that replication of the important picornavirus pathogen foot-and-mouth disease virus (FMDV in the presence of increasing concentrations of ribavirin results in the sequential incorporation of three amino acid substitutions (M296I, P44S and P169S in the viral polymerase (3D. The main biological effect of these substitutions is to attenuate the consequences of the mutagenic activity of ribavirin -by avoiding the biased repertoire of transition mutations produced by this purine analogue-and to maintain the replicative fitness of the virus which is able to escape extinction by ribavirin. This is achieved through alteration of the pairing behavior of ribavirin-triphosphate (RTP, as evidenced by in vitro polymerization assays with purified mutant 3Ds. Comparison of the three-dimensional structure of wild type and mutant polymerases suggests that the amino acid substitutions alter the position of the template RNA in the entry channel of the enzyme, thereby affecting nucleotide recognition. The results provide evidence of a new mechanism of resistance to a mutagenic nucleoside analogue which allows the virus to maintain a balance among mutation types introduced into progeny genomes during replication under strong mutagenic pressure.

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.

Rhodosporidium toruloides BANNO: Dose-response relationship, mutagenic efficiency and spectrum of mutants of auxotrophy-producing mutations induced by ultraviolet light and N-methyl-N'-nitro-N-nitrosoguanidine

International Nuclear Information System (INIS)

Boettcher, F.; Samsonova, I.A.

1978-01-01

The kinetics, efficiency, and specificity of induction of forward mutations to auxotrophy by ultraviolet light (UV) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was examined in stationary phase cells of Rhodosporidium (Rhodotorula) wild strain Rg1. In comparison to the spontaneous level the frequency of auxotrophic mutants was increased more than 1000 times by both mutagens, however, the mutagenic efficiency of MNNG was higher than that of UV. We found that the forward mutation rate is a linear function of the applicated UV and MNNG doses in the range to 600 J m -2 or 25 mM x min, respectively. The 35 studied biosynthetic pathways to amino acids, purines, pyrimidines, and vitamins are genetically blocked at different frequencies, but there is not any significant difference between UV and MNNG induced frequencies of mutants with a specific requirement. However, in difference to the approximately equal distribution of the MNNG-induced nic mutants among the genetic blocks of the tryptophan-nicotinamide pathway, UV-induced nic mutants occurred with a higher frequency in the genes of the tryptophan pyrrolase and the 3-hydroxykynureninase than in the genes of the other enzymes of the pathway. (author)

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

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 ...

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...

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.

Elevated mutation rate during meiosis in Saccharomyces cerevisiae.

Science.gov (United States)

Rattray, Alison; Santoyo, Gustavo; Shafer, Brenda; Strathern, Jeffrey N

2015-01-01

Mutations accumulate during all stages of growth, but only germ line mutations contribute to evolution. While meiosis contributes to evolution by reassortment of parental alleles, we show here that the process itself is inherently mutagenic. We have previously shown that the DNA synthesis associated with repair of a double-strand break is about 1000-fold less accurate than S-phase synthesis. Since the process of meiosis involves many programmed DSBs, we reasoned that this repair might also be mutagenic. Indeed, in the early 1960's Magni and Von Borstel observed elevated reversion of recessive alleles during meiosis, and found that the revertants were more likely to be associated with a crossover than non-revertants, a process that they called "the meiotic effect." Here we use a forward mutation reporter (CAN1 HIS3) placed at either a meiotic recombination coldspot or hotspot near the MAT locus on Chromosome III. We find that the increased mutation rate at CAN1 (6 to 21 -fold) correlates with the underlying recombination rate at the locus. Importantly, we show that the elevated mutation rate is fully dependent upon Spo11, the protein that introduces the meiosis specific DSBs. To examine associated recombination we selected for random spores with or without a mutation in CAN1. We find that the mutations isolated this way show an increased association with recombination (crossovers, loss of crossover interference and/or increased gene conversion tracts). Polζ appears to contribute about half of the mutations induced during meiosis, but is not the only source of mutations for the meiotic effect. We see no difference in either the spectrum or distribution of mutations between mitosis and meiosis. The correlation of hotspots with elevated mutagenesis provides a mechanism for organisms to control evolution rates in a gene specific manner.

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.

Analysis of mutagenic effects induced by carbon beams at different LET in a red yeast strain

International Nuclear Information System (INIS)

Sun Haining; Wang Jufang; Ma Shuang; Lu Dong; Wu Xin; Li Wenjian

2011-01-01

To evaluate inactive and mutagenic effects of carbon beam at different LET, the inactivation cross section and mutation cross section induced by carbon beams of different LET values were investigated in a red yeast strain Rhodotorula glutinis AY 91015. It was found that the maximum inactivation cross section of 4.37μm 2 , which was very close to the average nucleus cross section, was at LET of 120.0 keV/μm. The maximum mutation cross section was at LET of 96.0 keV/μm. Meanwhile, the highest mutagenicity of carbon ion was found around 58.2 keV/μm. It implied that the most efficient LET to induce mutation in survival yeasts was 58.2 keV/μm, which corresponded to energy of 35 MeV/u carbon beam. The most effective carbon beam to induce inactivation and mutation located at different energy region. (authors)

Induction of mutations by chemicals and gamma rays in mutants of yeast refractory to UV-mutagenesis

International Nuclear Information System (INIS)

Nasim, A.; Hannan, M.A.

1977-01-01

Radiation-sensitive mutants of Schizosaccharomyces pombe, known to be refractory to UV-mutagenesis, were tested for mutability caused by treatments with chemicals and gamma rays. One such mutant (rad3) was studied over a wide range of UV doses to compare the kinetics of its mutational response to that of the wild type. All such comparisons were carried out using a forward mutation system. Data show that, unlike UV, the chemical mutagens as well as gamma rays produced mutations (although at reduced frequency), in the strains of S. pombe tested, indicating the existence of an additional mechanism(s) for chemical and gamma ray induced mutations. These observations are discussed as these relate to the pathways for repair of mutational damage in yeast. (author)

Use of physical/chemical mutagens in plant breeding program in Vietnam

International Nuclear Information System (INIS)

Tran Duy Quy; Nguyen Huu Dong; Bui Huy Thuy; Le Van Nha; Nguyen Van Bich

2001-01-01

Among more than 1870 new plant varieties formed by mutation breeding in the world, 44 varieties of different plants were formed by Vietnamese scientists. Research on induced mutation in Vietnam started in 1966, was promoted in Agricultural Institute, Cuu Long Delta Rice Research Institute, Institute of Food Crop Research, and Agriculture Universities, and has produced varieties of rice, maize, soybean, peanut, tomato, jujuba, green bean etc using physical and chemical mutagens: Irradiation with gamma rays or neutrons, and use of such chemicals as dimethylsulfate (DMS), diethylsulfate (DES), ethyleneimine (EI), N-nitrosomethylurea (NUM), N-nitrosoethylurea (NEU), and sodium azide (NaN 3 ). In the present report, the results of cytological and genetic effects in M1 plants, the frequency and spectrum of chlorophyll and morphological mutants, the mutants obtained and the genetic nature of the next generation are described, particularly for the case of rice. Radiation dose and dose rate used as mutagens are also reported. (S. Ohno)

Use of physical/chemical mutagens in plant breeding program in Vietnam

Energy Technology Data Exchange (ETDEWEB)

Tran Duy Quy; Nguyen Huu Dong; Bui Huy Thuy; Le Van Nha; Nguyen Van Bich [Agricultural Genetics Institute, Hanoi (Viet Nam)

2001-03-01

Among more than 1870 new plant varieties formed by mutation breeding in the world, 44 varieties of different plants were formed by Vietnamese scientists. Research on induced mutation in Vietnam started in 1966, was promoted in Agricultural Institute, Cuu Long Delta Rice Research Institute, Institute of Food Crop Research, and Agriculture Universities, and has produced varieties of rice, maize, soybean, peanut, tomato, jujuba, green bean etc using physical and chemical mutagens: Irradiation with gamma rays or neutrons, and use of such chemicals as dimethylsulfate (DMS), diethylsulfate (DES), ethyleneimine (EI), N-nitrosomethylurea (NUM), N-nitrosoethylurea (NEU), and sodium azide (NaN{sub 3}). In the present report, the results of cytological and genetic effects in M1 plants, the frequency and spectrum of chlorophyll and morphological mutants, the mutants obtained and the genetic nature of the next generation are described, particularly for the case of rice. Radiation dose and dose rate used as mutagens are also reported. (S. Ohno)

Genetic effects of decay of tritium incorporated into cells of yeast Saccharomyces cerevisiae. 5. Lethal and mutagenic effects and the nature of mutations induced by /sup 3/H decay in the 6-th position of thymine

Energy Technology Data Exchange (ETDEWEB)

Ivanov, E.L.; Korolev, V.G. (AN SSSR, Leningrad. Inst. Yadernoj Fiziki)

1982-03-01

Lethal and mutagenous effects as well as nature of mutations induced with /sup 3/H decay in the sixth position of thymine (6-/sup 3/H-T) have been studied. Inactivation probability of haploid yeasts constituted ..cap alpha..=(6.1+-1.0)x10/sup -3/ decay/sup -1/ or ..cap alpha..=(7.6+-1.3)x10/sup -5/ rad/sup -1/, and probability of mutation appearance in genes ade 1, ade -K is (2.8+-1.7)x10/sup -8/ decay/sup -1/ or K=(3.5+-2.1)x10/sup -10/ rad/sup -1/. Lethal and mutageneous effects of 6-/sup 3/H-T don't differ considerably from those for /sup 3/H decay in the fifth position of thymine (5-/sup 3/H-T). From the point of view of frequency of transversions and mutations of read-out frame shift type induced in ade 2 gene, 6-/sup 3/H-T doesn't differ from 5-/sup 3/H-T. However, in comparison with the latter 6-/sup 3/H-T causes appearance of a larger amount of AT ..-->.. GTs transitions. A scheme, according to which 5 methyl barbituric acid (5MBK) is a finite product of /sup 3/H decay in the sixth position of thymine, is suggested. The results obtained point to that fact that 5MBK represents weak mutageneous damage of thymine causing the exchange of AT pair.

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

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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.

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

Mutation induction in repair-deficient strains of Drosophila

International Nuclear Information System (INIS)

Wuergler, F.E.; Graf, U.

1980-01-01

Experimental evidence indicates a polygenic control of mutagenesis in Drosophila melanogaster. In oocytes chromosome aberrations detected as half-translocations or dominant lethals depend on a repair system which in a number of genetically nonrelated strains shows different repair capacities. Sister chromatid exchanges are easily studied as ring chromosome losses. They develop through a genotype controlled mechanism from, premutational lesions. Stocks with particular pairs of third chromosomes were discovered in which increased sensitivity of larvae to the toxic effects of a monofunctional alkylating agent correlates with high frequencies of x-ray induced SCE's. Sex-linked mutagen-sensitive mutants could be shown to control mutation fixation: pronounced maternal effects were found when sperm carrying particular types of premutational lesions were introduced into different types of mutant oocytes. The mutant mus(1)101D1 was found to be unable to process lesions induced by the crosslinking agent nitrogen mustard into point mutations. Alkylation damage leads to increased point mutation frequencies in the excision repair deficient mutant mei-9L1, but to reduced frequencies in the post-replication repair deficient mutant mei-41D5. It became clear that the study of maternal effects on mutagenized sperm represents an efficient tool to analyze the gentic control of mutagenesis in the eukaryotic genome of Drosophila melanogaster

Evaluation of 10 Jet Fuels in the Salmonella-Escherichia coli Mutagenicity Assay

Science.gov (United States)

2016-09-07

Department of Defense, nor the U.S. Government. This work was funded by work unit number 60769 and the Defense Logistics Agency (provided to Dr...mutagenicity in the bacterial reverse mutation assay using Salmonella and E. coli strains. Based on the parameters used in this in vitro study, Citgo JP8 (POSF...471 (Bacterial Reverse Mutation Test) and the U.S. Environmental Protection Agency (EPA) Health Effects Test Guidelines OPPTS 870.5100 (Bacterial

Determination of somatic mutations in human erythrocytes by cytometry

International Nuclear Information System (INIS)

Jensen, R.H.; Langlois, R.G.; Bigbee, W.L.

1985-01-01

Flow cytometric assays of human erythrocytes labeled with monoclonal antibodies specific for glycophorin A were used to enumerate variant cells that appear in peripheral blood as a result of somatic gene-loss mutations in erythrocyte precursor cells. The assay was performed on erythrocytes from 10 oncology patients who had received at least one treatment from radiation or mutagenic chemotherapy at least 3 weeks before being assayed. The patients were suffering from many different malignancies (e.g., breast, renal, bone, colon and lung), and were treated with several different mutagenic therapeutics (e.g., cisplatinum, adriamycin, daunomycin, or cyclophosphamide). The frequency of these variant cells is an indication of the amount of mutagenic damage accumulated in the individual's erythropoietic cell population. Comparing these results to HPRT clonogenic assays, we find similar baseline frequencies of somatic mutation as well as similar correlation with mutagenic exposures. 9 refs., 3 figs., 1 tab

Determination of somatic mutations in human erythrocytes by cytometry

Energy Technology Data Exchange (ETDEWEB)

Jensen, R.H.; Langlois, R.G.; Bigbee, W.L.

1985-06-21

Flow cytometric assays of human erythrocytes labeled with monoclonal antibodies specific for glycophorin A were used to enumerate variant cells that appear in peripheral blood as a result of somatic gene-loss mutations in erythrocyte precursor cells. The assay was performed on erythrocytes from 10 oncology patients who had received at least one treatment from radiation or mutagenic chemotherapy at least 3 weeks before being assayed. The patients were suffering from many different malignancies (e.g., breast, renal, bone, colon and lung), and were treated with several different mutagenic therapeutics (e.g., cisplatinum, adriamycin, daunomycin, or cyclophosphamide). The frequency of these variant cells is an indication of the amount of mutagenic damage accumulated in the individual's erythropoietic cell population. Comparing these results to HPRT clonogenic assays, we find similar baseline frequencies of somatic mutation as well as similar correlation with mutagenic exposures. 9 refs., 3 figs., 1 tab.

Effects of mutagen application of sodium azide and gamma radiation in rice seeds

International Nuclear Information System (INIS)

Guimaraes, E.P.

1980-01-01

Effects of mutagen application of sodium azide and gamma radiation in rice seeds. Upland rice seeds, variety Dourado Precoce, were treated with gamma-rays and sodium azide(SA). Biological effects of these treatments were studied in the M 1 and M 2 generations. Survival number, seedling height, plant fertility and chlorophyill mutation frequencies based on mutations per 100 M 1 panicles and mutants per 100 M 2 seedlings were analysed. Among these characters, plant fertility was the most sensitive for mutagen treatments, and higher doses of gamma-rays or higher concentrations of sodium azide reduced significantly fertility of M 1 plants. The same effect as increase of concentration of sodium azide was observed when the acidity of buffer solution was increased, or when seeds were pre-treated in distilled water. The maximum chlorophyll mutation frequencies were obtained in sodium azide treatments: 40.74% in the M 1 panicles and 10.67% in the M 2 seedlings, in comparison with the maximum frequenies in gamma-irradiation of 10.39% in the M 1 panicles and 1.73% in the M 2 seedlings. (Author) [pt

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.)

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)

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.

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

Progress of mutation breeding in Thailand

Energy Technology Data Exchange (ETDEWEB)

Purivirojkul, Watchara; Vithayatherarat, Pradab [Pathumthani Rice Research Center (Thailand)

2001-03-01

The objectives in rice improvement in Thailand are to improve not only for high yielding and good grain quality but also for resistance to diseases and insects and tolerance to biotic stresses. Brief history of research and progress in rice mutation breeding in Thailand is presented. It includes the varieties of method such as using gamma rays, fast neutron and chemical mutagens, for example EMS (ethylmethane sulfonate) and EI (ethylene imine) for mutation works. Among all, improvements of Pathumthani 60 for short-statured plant type, RD23 for blast resistance, Basmati 370 for short-statured plant type, and Pra Doo Daeng for short-statured plant type and awnless grain are reported. To conclude, it is important to find the adequate doses of mutagen treatments that give maximum mutation frequencies, to know the optimal treatments or proper selection methods and to have well-defined objectives to create the success of mutation breeding. (S. Ohno)

Progress of mutation breeding in Thailand

International Nuclear Information System (INIS)

Purivirojkul, Watchara; Vithayatherarat, Pradab

2001-01-01

The objectives in rice improvement in Thailand are to improve not only for high yielding and good grain quality but also for resistance to diseases and insects and tolerance to biotic stresses. Brief history of research and progress in rice mutation breeding in Thailand is presented. It includes the varieties of method such as using gamma rays, fast neutron and chemical mutagens, for example EMS (ethylmethane sulfonate) and EI (ethylene imine) for mutation works. Among all, improvements of Pathumthani 60 for short-statured plant type, RD23 for blast resistance, Basmati 370 for short-statured plant type, and Pra Doo Daeng for short-statured plant type and awnless grain are reported. To conclude, it is important to find the adequate doses of mutagen treatments that give maximum mutation frequencies, to know the optimal treatments or proper selection methods and to have well-defined objectives to create the success of mutation breeding. (S. Ohno)

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

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

Photosynthetic and biochemical mechanisms of an EMS-mutagenized cowpea associated with its resistance to cowpea severe mosaic virus.

Science.gov (United States)

Souza, Pedro F N; Silva, Fredy D A; Carvalho, Fabricio E L; Silveira, Joaquim A G; Vasconcelos, Ilka M; Oliveira, Jose T A

2017-01-01

The seed treatment of a CPSMV-susceptible cowpea genotype with the mutagenic agent EMS generated mutagenized resistant plantlets that respond to the virus challenge by activating biochemical and physiological defense mechanisms. Cowpea is an important crop that makes major nutritional contributions particularly to the diet of the poor population worldwide. However, its production is low, because cowpea is naturally exposed to several abiotic and biotic stresses, including viral agents. Cowpea severe mosaic virus (CPSMV) drastically affects cowpea grain production. This study was conducted to compare photosynthetic and biochemical parameters of a CPSMV-susceptible cowpea (CE-31 genotype) and its derived ethyl methanesulfonate-mutagenized resistant plantlets, both challenged with CPSMV, to shed light on the mechanisms of virus resistance. CPSMV inoculation was done in the fully expanded secondary leaves, 15 days after planting. At 7 days post-inoculation, in vivo photosynthetic parameters were measured and leaves collected for biochemical analysis. CPSMV-inoculated mutagenized-resistant cowpea plantlets (MCPI) maintained higher photosynthesis index, chlorophyll, and carotenoid contents in relation to the susceptible (CE-31) CPSMV-inoculated cowpea (CPI). Visually, the MCPI leaves did not exhibit any viral symptoms neither the presence of the virus as examined by RT-PCR. In addition, MCPI showed higher SOD, GPOX, chitinase, and phenylalanine ammonia lyase activities, H 2 O 2 , phenolic contents, and cell wall lignifications, but lower CAT and APX activities in comparison to CPI. All together, these photosynthetic and biochemical changes might have contributed for the CPSMS resistance of MCPI. Contrarily, CPI plantlets showed CPSMV accumulation, severe disease symptoms, reduction in the photosynthesis-related parameters, chlorophyll, carotenoid, phenolic compound, and H 2 O 2 contents, in addition to increased β-1,3-glucanase, and catalase activities that might have

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

Formaldehyde-induced mutations in Drosophila melanogaster in dependence of the presence of acids

Energy Technology Data Exchange (ETDEWEB)

Stumm-Tegethoff, B F.A.

1969-01-01

The mutagenic activity of various combinations of formaldehyde, formic acid, acetic acid and hydrochloric acid was investigated by a sex-linked lethal test. All combinations were mutagenic and showed a mutation pattern from which it is concluded that in feeding experiments spermatocytes I are especially sensitive to the pairs of chemicals tested. In vapour experiments all germ cell stages were found to be susceptible. The presence of volatile acids was found to be necessary for the mutagenic activity of formaldehyde in the vapour state. Mutagenic effects were also observed in larval feeding experiments, in which only these acids were added to the medium. Experiments with stabilized pH at 7.5 did not show a significant mutagenic effect of formaldehyde. It is postulated that the tested agents are catalase inhibitors, which promote the formation of peroxides or free radicals which interfere with DNA replication, thus producing mutations.

Mutation breeding in malting barley

Energy Technology Data Exchange (ETDEWEB)

Hiraki, Makoto; Sanada, Matsuyoshi

1984-03-01

The released varieties of malting barley through mutation breeding is more than ten in number, including foreign varieties. In Japan four varieties has been released so far. We started mutation breeding in 1956 together with cross breeding that we employed before. Until now, Gamma 4, Amagi Nijo 1 and Fuji Nijo 2 have been produced from the direct use of induced mutations and Nirasaki Nijo 8 from the indirect use of them. Mutation breeding has been used mainly in the partial improvement of agronomic characteristics since the selection for malting quality was very complicated. As the variety bred by induced mutation is usually equivalent to the original variety in malting quality, both this new variety and the original one could be cultivated in the same area without any problem on later malt production. Particularly when one farmer cultivates barley in an extensive acreage, he can harvest at the best time according to the different maturing time of each variety. From these points of view, mutation breeding is an efficient tool in malting barley breeding. Mutagens we have used so far are X-rays, ..gamma..-rays, neutron and chemicals such as dES. From our experience in selection, the low dose of radiation and chemical mutagens are more effective in selection of point mutation than the high dose of radiation which tends to produce many abnormal but few practical mutants. (author).

Inactive and mutagenic effects induced by carbon beams of different LET values in a red yeast strain

International Nuclear Information System (INIS)

Wang Jufang; Lu Dong; Wu Xin; Sun Haining; Ma Shuang; Li Renmin; Li Wenjian

2010-01-01

To evaluate biological action of microorganism exposed to charged particles during the long distance space exploration, induction of inactivation and mutation in a red yeast strain Rhodotorula glutinis AY 91015 by carbon beams of different LET values (14.9-120.0 keV μm -1 ) was investigated. It was found that survival curves were exponential, and mutation curves were linear for all LET values. The dependence of inactivation cross section on LET approached saturation near 120.0 keV μm -1 . The mutation cross section saturated when LET was higher than 58.2 keV μm -1 . Meanwhile, the highest RBE i for inactivation located at 120.0 keV μm -1 and the highest RBE m for mutation was at 58.2 keV μm -1 . The experiments imply that the most efficient mutagenic part of the depth dose profile of carbon ion is at the plateau region with intermediate LET value in which energy deposited is high enough to induce mutagenic lesions but too low to induce over kill effect in the yeast cells.

Inactive and mutagenic effects induced by carbon beams of different LET values in a red yeast strain

Science.gov (United States)

Wang, Jufang; Lu, Dong; Wu, Xin; Sun, Haining; Ma, Shuang; Li, Renmin; Li, Wenjian

2010-09-01

To evaluate biological action of microorganism exposed to charged particles during the long distance space exploration, induction of inactivation and mutation in a red yeast strain Rhodotorula glutinis AY 91015 by carbon beams of different LET values (14.9-120.0 keV μm -1) was investigated. It was found that survival curves were exponential, and mutation curves were linear for all LET values. The dependence of inactivation cross section on LET approached saturation near 120.0 keV μm -1. The mutation cross section saturated when LET was higher than 58.2 keV μm -1. Meanwhile, the highest RBE i for inactivation located at 120.0 keV μm -1 and the highest RBE m for mutation was at 58.2 keV μm -1. The experiments imply that the most efficient mutagenic part of the depth dose profile of carbon ion is at the plateau region with intermediate LET value in which energy deposited is high enough to induce mutagenic lesions but too low to induce over kill effect in the yeast cells.

Radiation induced chlorophyll mutations in rice

International Nuclear Information System (INIS)

Bari, G.; Mustafa, G.; Soomro, A.M.; Baloch, A.W.

1985-01-01

Air dried grains of four local varieties of rice were treated with gamma-rays and fast neutrons for determining their mutagenic effectiveness through the occurence of chlorophyll mutations. Fast neutrons were more effective in inducing chlorophyll mutations and the rice variety Basmati 370 produced maximum number of mutations followed by varieties Sonahri Sugdasi, Jajai 77 and Sada Gulab. The highest frequency of chlorophyll mutations was that of albina types followed by striata types. The xantha, viridis and tigrina types of mutations were less frequent. (authors)

Mutation breeding newsletter. No. 44

International Nuclear Information System (INIS)

1999-04-01

This issue of the Newsletter presents research reports on the role of radiation induced mutation and chemical mutagens in improving productivity, disease resistance; cold and salinity tolerance of various crops and ornamental plants

The use of radiations to induce useful mutations in fruit trees

International Nuclear Information System (INIS)

Donini, B.

1976-01-01

The researches carried out at Casaccia in this field had covered the problems of technique of mutagenic treatment, mechanism of mutation induction and methodology of somatic mutation isolation. To enhance the efficiency of somatic mutation induction several conditions during and after the treatment have been studied. More experience has been gained with regard to the induction of somatic mutation which raises from genetical event or by tissue arrangement of a chimaeric shoot apex. To increase the size of mutated sector treatment have been carried out on the primordia in a very early stages and to improve the methodology of somatic mutation special techniques have been adapted of handling the material in the propagation. Possibility for early detection of mutants has been explored in cherry by establishing a correlation between mutants and hormonal content. By using the above mentioned techniques, useful mutants have been isolated in cherries, grapes, olives and peaches. (author)

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

How stable are the mutagenic tautomers of DNA bases?

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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

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

Inhibition of Bcl-2 or IAP proteins does not provoke mutations in surviving cells

Energy Technology Data Exchange (ETDEWEB)

Shekhar, Tanmay M. [Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083 (Australia); Green, Maja M. [Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083 (Australia); Department of Anatomy & Neuroscience, The University of Melbourne, Parkville 3010 (Australia); Rayner, David M.; Miles, Mark A.; Cutts, Suzanne M. [Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083 (Australia); Hawkins, Christine J., E-mail: c.hawkins@latrobe.edu.au [Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083 (Australia)

2015-07-15

Graphical abstract: - Highlights: • Mutagenicities of anti-cancer drugs were tested using HPRT, γH2AX and comet assays. • TRAIL, doxorubicin and etoposide were more mutagenic than BH3- or Smac-mimetics. • Physiologically achievable levels of the BH3-mimetic ABT-737 were not mutagenic. • High concentrations of ABT-737 provoked mutations via an off-target mechanism. • Even very high concentrations of IAP antagonists were not mutagenic. - Abstract: Chemotherapy and radiotherapy can cause permanent damage to the genomes of surviving cells, provoking severe side effects such as second malignancies in some cancer survivors. Drugs that mimic the activity of death ligands, or antagonise pro-survival proteins of the Bcl-2 or IAP families have yielded encouraging results in animal experiments and early phase clinical trials. Because these agents directly engage apoptosis pathways, rather than damaging DNA to indirectly provoke tumour cell death, we reasoned that they may offer another important advantage over conventional therapies: minimisation or elimination of side effects such as second cancers that result from mutation of surviving normal cells. Disappointingly, however, we previously found that concentrations of death receptor agonists like TRAIL that would be present in vivo in clinical settings provoked DNA damage in surviving cells. In this study, we used cell line model systems to investigate the mutagenic capacity of drugs from two other classes of direct apoptosis-inducing agents: the BH3-mimetic ABT-737 and the IAP antagonists LCL161 and AT-406. Encouragingly, our data suggest that IAP antagonists possess negligible genotoxic activity. Doses of ABT-737 that were required to damage DNA stimulated Bax/Bak-independent signalling and exceeded concentrations detected in the plasma of animals treated with this drug. These findings provide hope that cancer patients treated by BH3-mimetics or IAP antagonists may avoid mutation-related illnesses that afflict

Inhibition of Bcl-2 or IAP proteins does not provoke mutations in surviving cells

International Nuclear Information System (INIS)

Shekhar, Tanmay M.; Green, Maja M.; Rayner, David M.; Miles, Mark A.; Cutts, Suzanne M.; Hawkins, Christine J.

2015-01-01

Graphical abstract: - Highlights: • Mutagenicities of anti-cancer drugs were tested using HPRT, γH2AX and comet assays. • TRAIL, doxorubicin and etoposide were more mutagenic than BH3- or Smac-mimetics. • Physiologically achievable levels of the BH3-mimetic ABT-737 were not mutagenic. • High concentrations of ABT-737 provoked mutations via an off-target mechanism. • Even very high concentrations of IAP antagonists were not mutagenic. - Abstract: Chemotherapy and radiotherapy can cause permanent damage to the genomes of surviving cells, provoking severe side effects such as second malignancies in some cancer survivors. Drugs that mimic the activity of death ligands, or antagonise pro-survival proteins of the Bcl-2 or IAP families have yielded encouraging results in animal experiments and early phase clinical trials. Because these agents directly engage apoptosis pathways, rather than damaging DNA to indirectly provoke tumour cell death, we reasoned that they may offer another important advantage over conventional therapies: minimisation or elimination of side effects such as second cancers that result from mutation of surviving normal cells. Disappointingly, however, we previously found that concentrations of death receptor agonists like TRAIL that would be present in vivo in clinical settings provoked DNA damage in surviving cells. In this study, we used cell line model systems to investigate the mutagenic capacity of drugs from two other classes of direct apoptosis-inducing agents: the BH3-mimetic ABT-737 and the IAP antagonists LCL161 and AT-406. Encouragingly, our data suggest that IAP antagonists possess negligible genotoxic activity. Doses of ABT-737 that were required to damage DNA stimulated Bax/Bak-independent signalling and exceeded concentrations detected in the plasma of animals treated with this drug. These findings provide hope that cancer patients treated by BH3-mimetics or IAP antagonists may avoid mutation-related illnesses that afflict

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...

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...

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

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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.

Prospects for cellular mutational assays in human populations

International Nuclear Information System (INIS)

Mendelsohn, M.L.

1985-01-01

Practical, sensitive, effective, human cellular assays for detecting somatic and germinal mutations would have great value in environmental mutagenesis and carcinogenesis. When available, such assays should allow us to fill the void between human mutagenicity and the data that exist from short-term tests and from mutagenicity in other species. We will be able to validate the role of somatic mutations in carcinogenesis, to identify environmental factors that affect human germ cells, to integrate the effects of complex mixtures and the environment in the human subject, and to identify people who are hypersusceptible to genetic injury. Human cellular mutational assays, particularly when combined with cytogenetic and heritable mutational tests, promise to play pivotal roles in estimating the risk from low-dose radiation and chemical exposures. These combined methods avoid extrapolations of dose and from species to species, and may be sensitive enough and credible enough to permit politically, socially and scientifically acceptable risk management. 16 references

Possibilities for raising the mutagenic effect of gamma rays by means of some sentizers in Scenedesmus acutus

International Nuclear Information System (INIS)

Mekhandzhiev, A.D.; Nikolov, N.N.; Sultanova, E.V.

1985-01-01

Treatment with haematoporphyrin and iodacetamide in unicellular green alga Scenedesmus acutus (Meyen) str.8 Tomaselli was applied. Data are presented about the frequency of the induced mutations demonstrating the presence of quite specific effects due to the type and concentration of the compound used. The investigated compounds have shown influence also on the spectrum of the mutations obtained. By means of modification of the mutagenic effect of the gamma rays it is possible to bring about an increase in the mutation variability and to introduce essential changes in the spectrum of the mutations, a fact significant to mutation genetics

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.

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.

Research progress on the space-flight mutation breeding of woodyplant

International Nuclear Information System (INIS)

Cui Binbin; Sun Yuhan; Li Yun

2013-01-01

The space-flight mutation breeding conception, characteristics, mutagenic effects, research progress at home and abroad in woody plant were reviewed in this paper. Compared with crops, although the research of the woody plants space-flight mutation breeding in China started later, but it has developed rapidly and has gotten certain achievement. Now the satellite and high-altitude balloon experiment were conducted with over 20 tree species such as Populus ussuriensis and 50 flower species such as Paeonia suffruticosa. The above work will has profound significance for space-flight breeding technology application on woody plants. In the end, this thesis analyzes the prospect in the future from four aspects such as using woody plants asexual reproduction characteristic, strengthening the space mutation mechanism study, enhancing new space mutation varieties screen and strengthening ornamental specific types selection. This thesis also thinks that the space mutation breeding is expected to become an effective way in woody plant genetic breeding. (authors)

Inactive and mutagenic effects induced by carbon beams of different LET values in a red yeast strain

Energy Technology Data Exchange (ETDEWEB)

Wang Jufang, E-mail: jufangwang@impcas.ac.c [Institute of Modern Physics, Chinese Academy of Sciences, Nanchang Road No. 509, Lanzhou 730000 (China); Lu Dong; Wu Xin; Sun Haining; Ma Shuang; Li Renmin; Li Wenjian [Institute of Modern Physics, Chinese Academy of Sciences, Nanchang Road No. 509, Lanzhou 730000 (China)

2010-09-15

To evaluate biological action of microorganism exposed to charged particles during the long distance space exploration, induction of inactivation and mutation in a red yeast strain Rhodotorula glutinis AY 91015 by carbon beams of different LET values (14.9-120.0 keV {mu}m{sup -1}) was investigated. It was found that survival curves were exponential, and mutation curves were linear for all LET values. The dependence of inactivation cross section on LET approached saturation near 120.0 keV {mu}m{sup -1}. The mutation cross section saturated when LET was higher than 58.2 keV {mu}m{sup -1}. Meanwhile, the highest RBE{sub i} for inactivation located at 120.0 keV {mu}m{sup -1} and the highest RBE{sub m} for mutation was at 58.2 keV {mu}m{sup -1}. The experiments imply that the most efficient mutagenic part of the depth dose profile of carbon ion is at the plateau region with intermediate LET value in which energy deposited is high enough to induce mutagenic lesions but too low to induce over kill effect in the yeast cells.

A switch from high-fidelity to error-prone DNA double-strand break repair underlies stress-induced mutation.

Science.gov (United States)

Ponder, Rebecca G; Fonville, Natalie C; Rosenberg, Susan M

2005-09-16

Special mechanisms of mutation are induced in microbes under growth-limiting stress causing genetic instability, including occasional adaptive mutations that may speed evolution. Both the mutation mechanisms and their control by stress have remained elusive. We provide evidence that the molecular basis for stress-induced mutagenesis in an E. coli model is error-prone DNA double-strand break repair (DSBR). I-SceI-endonuclease-induced DSBs strongly activate stress-induced mutations near the DSB, but not globally. The same proteins are required as for cells without induced DSBs: DSBR proteins, DinB-error-prone polymerase, and the RpoS starvation-stress-response regulator. Mutation is promoted by homology between cut and uncut DNA molecules, supporting a homology-mediated DSBR mechanism. DSBs also promote gene amplification. Finally, DSBs activate mutation only during stationary phase/starvation but will during exponential growth if RpoS is expressed. Our findings reveal an RpoS-controlled switch from high-fidelity to mutagenic DSBR under stress. This limits genetic instability both in time and to localized genome regions, potentially important evolutionary strategies.

Performance of mutagen treated Jatropha curcas (Petro-crop) on alkali soil

International Nuclear Information System (INIS)

Pandey, R.K.; Datta, S.K.; Mishra, P.N.

1998-01-01

Under the user land development programme, seeds of Jatropha curcas (Euphorbiaces) were treated with 6, 12, 18 and 24 krad of gamma rays and sown in randomised block design on different grades of alkali soils. Wide range of variability could be detected in mutagen treated population. Results indicate that suitable strains of J. curcas can be isolated through mutation breeding programme for utilisation of user land. (author)

Use of mutagenous factors in the breeding of vegetatively propagated plants

International Nuclear Information System (INIS)

Dryagina, I.V.; Fomenko, N.N.

1978-01-01

Given is a review of the literature and authors data on using mutagenous factors with different nature to breed some new and useful forms of plants reproduced vegetatively. The problem history and prospects of the practical application of the method are stated. In particular the data on ionizing radiation use in fruit crop selection to breed mutation forms (effect on buds, pollen, seeds etc.) are presented

Induced mutations in highly heterozygous vegetatively propagated grasses

International Nuclear Information System (INIS)

Powell, J.B.

1976-01-01

Experience with mutation induction of turf and forage grasses indicates that much progress can be achieved by this method. More than 300 mutations have been produced in our laboratory in the cultivars Tifgreen and Tifdwarf bermudagrass (Cynodon sp.). In the Tifway and Tifcote bermudagrasses we have demonstrated similar mutation responses. The first three clones are triploids and Tifcote is a probable tetraploid. No seeds are set on these clones. Two clones of bermudagrass, Coastal and Coastcross-1, occupy millions of hectares in the USA. Both are mutable and are known to be hybrids with 36 chromosomes. Biotypes of dallisgrass (Paspalum dilatatum Poir.) exist with 40 and 50 chromosomes and reproduce as sexual and obligate apomictic forms. Gamma-ray and thermal-neutron treatment of seed of these biotypes produced mutants that maintained the maternal characteristics in subsequent generations. Bahiagrass (Paspalum notatum Fluegge) also has sexual and apomictic biotypes. Some success was indicated for increased seed set by mutagen treatment. Kentucky bluegrass (Poa pratensis L.) is a facultative apomict with varying numbers of chromosomes in different cultivars. Gamma-ray mutagen treatment of rhizomes produced numerous mutations for plant type and disease reaction. Most mutations perpetuate themselves through the seed. The characteristic in common with all these grasses is their heterozygosity, which is maintained by the vegetative propagation or apomictic mode of reproduction. The experience in using ionizing radiation to induce heritable changes in these vegetatively propagated grasses is one of considerable success. Mutation rates in some of these irradiated grasses exceeded 65% and aberrant plants with characteristics previously never observed were found. Numerous hemizygous and heterozygous loci seem to be a sensitive target for mutagens. (author)

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.)

Bystander effect-induced mutagenicity in HPRT locus of CHO cells following BNCT neutron irradiation: Characteristics of point mutations by sequence analysis

Energy Technology Data Exchange (ETDEWEB)

Kinashi, Yuko [Research Reactor Institute, Kyoto University, Kumatori-cho, Sennan-gun, Osaka (Japan)], E-mail: kinashi@rri.kyoto-u.ac.jp; Suzuki, Minoru; Masunaga, Shinichiro; Ono, Koji [Research Reactor Institute, Kyoto University, Kumatori-cho, Sennan-gun, Osaka (Japan)

2009-07-15

To investigate bystander mutagenic effects induced by alpha particles during boron neutron capture therapy (BNCT), we mixed cells that were electroporated with borocaptate sodium (BSH), which led to the accumulation of {sup 10}B inside the cells, with cells that did not contain the boron compound. BSH-containing cells were irradiated with {alpha} particles produced by the {sup 10}B(n,{alpha}){sup 7}Li reaction, whereas cells without boron were only affected by the {sup 1}H(n,{gamma}){sup 2}H and {sup 14}N(n,{rho}){sup 14}C reactions. The frequency of mutations induced in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus was examined in Chinese hamster ovary (CHO) cells irradiated with neutrons (Kyoto University Research Reactor: 5 MW). Neutron irradiation of 1:1 mixtures of cells with and without BSH resulted in a survival fraction of 0.1, and the cells that did not contain BSH made up 99.4% of the surviving cell population. Using multiplex polymerase chain reactions (PCRs), molecular structural analysis indicated that most of the mutations induced by the bystander effect were point mutations and that the frequencies of total and partial deletions induced by the bystander effect were lower than those resulting from the {alpha} particles produced by the {sup 10}B(n,{alpha}){sup 7}Li reaction or the neutron beam from the {sup 1}H(n,{gamma}){sup 2}H and {sup 14}N(n,{rho}){sup 14}C reactions. The types of point mutations induced by the BNCT bystander effect were analyzed by cloning and sequencing methods. These mutations were comprised of 65.5% base substitutions, 27.5% deletions, and 7.0% insertions. Sequence analysis of base substitutions showed that transversions and transitions occurred in 64.7% and 35.3% of cases, respectively. G:C{yields}T:A transversion induced by 8-oxo-guanine in DNA occurred in 5.9% of base substitution mutants in the BNCT bystander group. The characteristic mutations seen in this group, induced by BNCT {alpha} particles

Verification of mutagen function of Zeocin in Nannochloropsis oceanica through transcriptome analysis

Science.gov (United States)

Lin, Genmei; Wang, Yamei; Guo, Li; Ding, Haiyan; Hu, Yongmei; Liang, Sijie; Zhang, Zhongyi; Yang, Guanpin

2017-06-01

Zeocin can cause double strand breaks of DNA and thus is frequently used as a selective antibiotic of eukaryotic Sh ble transformants. In non-transformation system, Zeocin may function as a mutagen if not totally lethal. To verify such function of Zeocin, we mutated Nannochloropsis oceanica by increasing the concentration of Zeocin in medium gradually, and isolated a N. oceanica strain (single cell culture) which survived Zeocin up to 10.0 μg mL-1. The Zeocin-tolerant strain entered the exponential growth phase later and grew slower than the wild strain. Transcriptome profiling showed that the Zeocin-tolerant N. oceanica strain survived Zeocin mainly by adapting (heritable), rather than acclimating (plastic) to Zeocin. Hence mutating N. oceanica with Zeocin was approved effective. Meanwhile, the physiological characteristics of this Zeocin-tolerant strain were demonstrated. As we proposed, N. oceanica tolerated Zeocin by strengthening its protein degradation and antioxidation. The genes controlling cell division and cellular response to stimuli may also have played important roles in the reduction of growth and the tolerance to Zeocin. Our findings evidenced that Zeocin can serve as an appropriate mutagen of microalgae. Creating variations through mutation with Zeocin may help to study the genetic basis of the traits of this monoploidy and asexual microalga, as well as improve its production.

Mutagenic effect of radionuclides incorporated into DNA of Drosophila melanogaster. Progress report, 1978-1979

International Nuclear Information System (INIS)

Lee, W.R.

1979-01-01

Current progress in studies on the mutagenic effect of 3 H incorporated into the DNA of Drosophila melanogaster is reported. It was shown that selected 3 H precursors incorporated into DNA are metabolized. The forms (metabolites) of tritium found in the DNA molecules and the mutation frequencies resulting therefrom were identified. An alcohol dehydrogenase system was developed for recovering mutations that is capable of distinguishing between base changes and chain breakage events that may lead to the formation of deletions

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

Mutagenic synergism detected between 1,2-dibromoethane and X rays in the stamen hairs of Tradescantia clone BNL 4430

International Nuclear Information System (INIS)

Xiao, Ling Zhi; Ichikawa, Sadao

1998-01-01

Mutagenic interaction between 1,2-dibromoethane (EDB) and X rays was studied in the stamen hairs of Tradescantia clone BNL 4430, a blue/pink heterozygote. The young inflorescence-bearing shoots with roots of this clone cultivated in a nutrient solution circulating growth chamber were used as the tester plants. EDB is a promutagen and also a bifunctional alkylating agent with a high Swain-Scott substrate constant, but is thought to react probably via SN 1 mechanism. After confirming the dose-dependent mutagenicities of aqueous solutions of EDB for the first time in Tradescantia stamen hairs, a combined treatment with EDB and X rays was conducted, exposing acutely to 578 mGy X rays at the midpoint of 66.5 mM EDB treatment for 4 h. The induced somatic mutation frequency determined after the combined treatment was significantly higher (at 0.1% level) than that expected from the additive effects of EDB and X rays, showing that EDB and X rays acted obviously synergistically. The confirmation of the mutagenic synergism between EDB and X rays is reported here for the first time, although a likelihood of synergistic effects of EDB with 3 H beta rays has been suggested earlier. (author)

Comparative studies of the induction of somatic eye-color mutations in an unstable strain of Drosophila melanogaster by MMS and X-rays at different developmental stages

International Nuclear Information System (INIS)

Rasmuson, Aa.

1985-01-01

The UZ system in Drosophila melanogaster can be used as a screening system for mutagens. This survey is an attempt to correlate the size of the mutated area of the eyes with the age of the larvae at mutagen treatment. X-rays and MMS were used to give an indication of the mechanism of the instability, according to the different kinds of DNA damage induced. The results show that the mean size of red spots decreased with increasing age of larvae at treatment, while the mutation frequencies were increased because of the multiplication of the cells in the eye anlage susceptible to the mutagens. Red spots induced with MMS are smaller in size than X-ray-induced red spots, indicating a delay in the establishment of mutations from chemically-induced lesions compared to irradiation damage. White spots on the other hand were equally large in size, irrespective of inducing agent and about twice the size of the chemically-induced red spots, implying a faster and more direct action for fixation of deletions than for the production of MMS induced shifts in eye color from zeste to red. (Auth.)

Induction of transposon TN1 translocation under the action of different mutagens

International Nuclear Information System (INIS)

Kubanejshvili, M.G.; Smirnov, S.P.; Tarasov, V.A.

1983-01-01

Migration of ampicillin transposon Tn1 under normal conditions in Escherichia coli cells proceeds with low frequency (10 -4 transpositions for cell). The low transposition frequency is conditioned by the transposition repression, realized by the gene-repressor in transposon structure and, probably, by other regulating genes of the bacterium-host. E. coli cell treatment by physical and chemical mutagens resulted in induction of translocation of ampicillin transposon Tn1 from plasmid RP4 into other replicons. Mitomycin C and ultraviolet radiation produced stronger inducing effect as compared to nitroso-guanidine (NG). The effect of the given mutagens on transposition Tn1 correlated with their activating capacity with respect to inducible SOS-functions of E coli. The mutation of rec A didn't influence on spontaneous Tn1 transposition, but blocked completely the induction of transposition process under mutagen effect. The relationship of inducible transposition with SOS-functions in E. coli cells, controlled by recA and lexA genes, as well as the possible role of the process in genetic microorganism variability are discussed in the paper

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

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.

Effect of single and combined treatment with gamma rays and some chemical mutagens in rice

International Nuclear Information System (INIS)

Lyong Van Hin; Mekhandzhiev, A.; Murzova, P.; Chilikov, I.

1991-01-01

Dry rice seeds of 3 cvs and 2 lines have been irradiated (Co 60 , 10 krad) and treated with 0.0012% sodium azide (NaN 3 ) and 0.2% ethylmethanesulfonate (EMS) in definite combinations. It is found that chlorophyll mutations are less frequent after single gamma irradiation. Sodium azide produces a higher percentage of mutations than EMS. Highest mutation frequency has been observed following combined treatment with gamma rays and chemical mutagens. The combined treatment has resulted in a considerably higher mutation effect than the theoretically expected one in the lines Nora and Mega, and in cv. Krasnodarski 424. Highest mutation spectrum has been found in cv. Krasnodarski 424 and in Nora line following combined treatment. 1 tab., 5 figs., 20 refs

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.

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

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

Mutagenicity of the potent rat hepatocarcinogen 6BT to the liver of transgenic (lacI) rats: consideration of a reduced mutation assay protocol.

Science.gov (United States)

Lefevre, P A; Tinwell, H; Ashby, J

1997-01-01

6-(p-dimethylaminophenylazo)benzothiazole (6BT) is an unusually potent rat hepatocarcinogen, producing large malignant liver tumours after only 2-3 months of dietary administration in a riboflavin-deficient diet. This azocarcinogen has been evaluated in a Big Blue F344 transgenic rat (lacI) gene mutation assay. In a reproduction of the early stages of the carcinogenesis bioassay of this agent, rats were maintained on a riboflavin-deficient diet and were given 10 consecutive daily doses of 6BT (10 mg/kg) by oral gavage. The animals were killed and the livers examined 11 days after the final dose. The livers of 6BT-treated rats showed evidence of hepatocellular hypertrophy in centrolobular areas, with some indication of an increased incidence of mitotic figures. An approximately 10-fold increase in the mutation frequency of DNA isolated from an aliquot of the combined liver homogenates of 6BT-treated rats was observed over that obtained from an equivalent aliquot from control animals. Examination of DNA samples isolated from the livers of individual animals confirmed that 6BT was mutagenic in Big Blue rat livers. These data extend the sensitivity of this transgenic assay to include azo hepatocarcinogens. The determination of mutation frequencies using pooled tissue samples represented a major resource-saving adaptation of the assay protocol in the present study; the general advantages and disadvantages of this practice are discussed.

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.

A genetic screen for mutations affecting embryonic development in medaka fish (Oryzias latipes).

Science.gov (United States)

Loosli, F; Köster, R W; Carl, M; Kühnlein, R; Henrich, T; Mücke, M; Krone, A; Wittbrodt, J

2000-10-01

In a pilot screen, we assayed the efficiency of ethylnitrosourea (ENU) as a chemical mutagen to induce mutations that lead to early embryonic and larval lethal phenotypes in the Japanese medaka fish, Oryzias latipes. ENU acts as a very efficient mutagen inducing mutations at high rates in germ cells. Three repeated treatments of male fish in 3 mM ENU for 1 h results in locus specific mutation rates of 1.1-1.95 x10(-3). Mutagenized males were outcrossed to wild type females and the F1 offspring was used to establish F2 families. F2 siblings were intercrossed and the F3 progeny was scored 24, 48 and 72 h after fertilization for morphological alterations affecting eye development. The presented mutant phenotypes were identified using morphological criteria and occur during early developmental stages of medaka. They are stably inherited in a Mendelian fashion. The high efficiency of ENU to induce mutations in this pilot screen indicates that chemical mutagenesis and screening for morphologically visible phenotypes in medaka fish allows the genetic analysis of specific aspects of vertebrate development complementing the screens performed in other vertebrate model systems.

Reaction mixtures formed by nitrite and selected sulfa-drugs showed mutagenicity in acidic medium

Directory of Open Access Journals (Sweden)

Claudia Trossero

2009-01-01

Full Text Available Nitrite, which is present in preserved meat and can be produced in the oral cavity by reduction of nitrate taken from vegetables, could react in stomach with nitrosatable drugs, giving genotoxic-carcinogenic N-nitroso compounds (NOC. The mutagenicity of reaction mixtures formed by sodium nitrite and selected sulfa-drugs (sulfathiazole, HST; phtalylsulfathiazole, PhST; complex Co(II-sulfathiazole, Co(II-ST in acidic medium was evaluated using the Salmonella typhimurium reverse mutation assay (Ames test, with TA98 and TA 100 strains. The reactions were carried out at room temperature, with a mole ratio [nitrite]/[sulfa-drug] > 1. The three reaction mixtures showed mutagenic effects in the considered range.

Induced mutations in sesame breeding

International Nuclear Information System (INIS)

Ashri, A.

2001-01-01

The scope of induced mutations in sesame (Sesamum indicum L.) breeding is reviewed. So far in Egypt, India, Iraq, Rep. of Korea, and Sri Lanka, 14 officially released varieties have been developed through induced mutations: 12 directly and 2 through cross breeding (one using the 'dt45' induced mutant from Israel). For another variety released in China there are no details. The induced mutations approach was adopted primarily in order to obtain genetic variability that was not available in the germplasm collection. The mutagens commonly applied have been gamma rays, EMS and sodium azide. Sesame seeds can withstand high mutagen doses, and there are genotypic differences in sensitivity between varieties. The mutants induced in the above named countries and others include better yield, improved seed retention, determinate habit, modified plant architecture and size, more uniform and shorter maturation period, earliness, resistance to diseases, genic male sterility, seed coat color, higher oil content and modified fatty acids composition. Some of the induced mutants have already given rise to improved varieties, the breeding value of other mutants is now being assessed and still others can serve as useful markers in genetic studies and breeding programmes. (author)

Gene mutations, chromosome aberrations and survival after X-ray irradiation of cultured Chinese hamster cells at cysteamine protection

International Nuclear Information System (INIS)

Elisova, I.V.; Feoktistova, I.P.

1983-01-01

The culture of Chinese hamster cells (clone 431) has been used to study cysteamine action on mutagenous effect of X-rays, determined by the induction of resistance of gene mutations to 6-thioguanine and chromosomal abberations, as well as on the reproductive form of death of irradiated cells. Dose--- effect curves are obtained under conditions of irradiation with and without protector. The factor of dose alteration is 2.0 for chromosomal aberrations and cell survival, and 2.8 for gene mutations. It is sUpposed that cysteamine affects the general mechanisms, which take part in the realis zation of injuries that bring about gene mutations, chromosomal aberrations and cell lethality

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)

Optimal control of gene mutation in DNA replication.

Science.gov (United States)

Yu, Juanyi; Li, Jr-Shin; Tarn, Tzyh-Jong

2012-01-01

We propose a molecular-level control system view of the gene mutations in DNA replication from the finite field concept. By treating DNA sequences as state variables, chemical mutagens and radiation as control inputs, one cell cycle as a step increment, and the measurements of the resulting DNA sequence as outputs, we derive system equations for both deterministic and stochastic discrete-time, finite-state systems of different scales. Defining the cost function as a summation of the costs of applying mutagens and the off-trajectory penalty, we solve the deterministic and stochastic optimal control problems by dynamic programming algorithm. In addition, given that the system is completely controllable, we find that the global optimum of both base-to-base and codon-to-codon deterministic mutations can always be achieved within a finite number of steps.

Effect of mutagens on the quality characters and disease resistant genes of diploid cotton (Gossypium arboreum L.)

International Nuclear Information System (INIS)

Haidar, S.; Khan, I.A.; Mansoor, S.

2002-01-01

In both M1 and M2 plant height decreased with the increase in dose for both the mutagens. The 15 Krad and 0.15M EMS doses increased 122.7 and 128.3 gm seed cotton yield as compared to control respectively while all other doses of both mutagens decreased the yield of seed cotton. The EMS dose 0.10 M drastically decreased 184 gm seed cotton yield as compared to control. There was no larger effect of both mutagens on GOT % whereas staple length was slightly increased and micronaire value decreased as compared to control for all the doses of both mutagens. It was observed in M2 that mutation dose 10 Krad increased 165.6 gm seed cotton yield as compared to control but slight reduction in GOT % was observed. In M2 GOT were increased 3.5 % with 15 Krad and 3.6 % with EMS 0.10 M as compared to control. There were no larger effects for both mutagens in case of staple length, micronaire and uniformity ratio for all the doses as compared to control. respectively. In both M1 and M2 no plant was observed susceptible to cotton leaf curl virus and bacterial blight diseases of cotton

Origin of Somatic Mutations in β-Catenin versus Adenomatous Polyposis Coli in Colon Cancer: Random Mutagenesis in Animal Models versus Nonrandom Mutagenesis in Humans.

Science.gov (United States)

Yang, Da; Zhang, Min; Gold, Barry

2017-07-17

Wnt signaling is compromised early in the development of human colorectal cancer (CRC) due to truncating nonsense mutations in adenomatous polyposis coli (APC). CRC induced by chemical carcinogens, such as heterocyclic aromatic amines and azoxymethane, in mice also involves dysregulation of Wnt signaling but via activating missense mutations in the β-catenin oncogene despite the fact that genetically modified mice harboring an inactive APC allele efficiently develop CRC. In contrast, activating mutations in β-catenin are rarely observed in human CRC. Dysregulation of the Wnt signaling pathway by the two distinct mechanisms reveals insights into the etiology of human CRC. On the basis of calculations related to DNA adduct levels produced in mouse CRC models using mutagens, and the number of stem cells in the mouse colon, we show that two nonsense mutations required for biallelic disruption of APC are statistically unlikely to produce CRC in experiments using small numbers of mice. We calculate that an activating mutation in one allele near the critical GSK3β phosphorylation site on β-catenin is >10 5 -times more likely to produce CRC by random mutagenesis due to chemicals than inactivating two alleles in APC, yet it does not occur in humans. Therefore, the mutagenesis mechanism in human CRC cannot be random. We explain that nonsense APC mutations predominate in human CRC because of deamination at 5-methylcytosine at CGA and CAG codons, coupled with the number of human colonic stem cells and lifespan. Our analyses, including a comparison of mutation type and age at CRC diagnosis in U.S. and Chinese patients, also indicate that APC mutations in CRC are not due to environmental mutagens that randomly damage DNA.

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

Cytotoxic and mutagenic effects of conventionally processed foods in comparison with irradiated foods

International Nuclear Information System (INIS)

Mohyuddin, M.

1975-05-01

Several kinds of spices and processed food namely onion, garlic, turmeric, red chillies, black pepper, cloves, cinnamon, simple curry, meat curry, curry prepared from irradiated onions and potatoes and curry from irradiated fish were tested for cytotoxocity and mutagenicity. Onion root tips were used in the studies of cytotoxicity. Pseudomonas fluorescens strain NCTC-9428, a streptomycin-sensitive strain, was used as the test organism in mutagenicity studies. Wide range of cytoxicity was observed in all spices and food tested, varying from 48% abnormality in root tips in black pepper to 97.7% in garlic extract. The degrees of cytotoxic abnormality of irradiated potatoes and onions appeared to be lower than in their control counterparts. The average percentages of cytotoxic abnormality in curry prepared from irradiated fish and the one prepared from irradiated potatoes and onions, at their original concentration, were 95.92% and 99.5% resp. Digesting curry prepared from irradiated potatoes and onions with bile salts appeared to show some detoxification characteristics. The mutation rate of Pseudomonas fluorescens grown in media containing unirradiated spice extract was significantly higher than in the control (media without spice extract). However, the mutation rate of an extract of irradiated onions (10 krad) showed no difference from the control. There was no difference in the mutation rate on extracts of curry prepared from irradiated onions and potatoes from the one prepared from unirradiated onions and potatoes

Mutation Induction with UV- and X-radiations in spores and vegetative cells of Bacillus subtilis

International Nuclear Information System (INIS)

Tanooka, H.; Munakata, N.; Kitahara, S.

1978-01-01

Spores and vegetative cells of Bacillus subtilis strains with various defects in DNA-repair capacities (hcr - , ssp - , hcr - ssp - ) were irradiated with UV radiation or X-rays. Induced mutation frequency was determined from the observed frequency of prototrophic reversion of a suppressible auxotropic mutation. At equal physical dose, after either UV- or X-irradiation, spores were more resistant to mutations as well as to killing than were vegetative cells. However, quantitative comparison revealed that, at equally lethal doses, spores and vegetative cells were almost equally mutable by X-rays whereas spores were considerably less mutable by UV than were vegetative cells. Thus, as judged from their mutagenic efficiency relative to the lethality, X-ray-induced damage in the spore DNA and the vegetative DNA were equally mutagenic, while UV-induced DNA photoproducts in the spore were less mutagenic than those in vegetative cells. Post-treatment of UV-irradiated cells with caffeine decreased the survival and the induced mutation frequency for either spores or vegetative cells for all the strains. In X-irradiated spores however, a similar suppressing effect of caffeine was observed only for mutability of a strain lacking DNA polymerase I activity

The evaluation of the Chernobyl reactor accident by the help of the Hungarian Surveillance of Germinal Mutations

International Nuclear Information System (INIS)

Czeizel, A.E.; Elek, Cs.; Susanszky, E.

1992-01-01

The germinal mutagenic consequences or radioactive fall-out deposition from the Chernobyl accident in Hungary was evaluated in the ongoing program on the population-based Hungarian Surveillance of Germinal Mutations. The surveillance is based on three groups of indicator conditions: 15 sentinel anomalies (indicators of germinal dominant gene mutations), Down syndrome (an indicator of germinal numerical and structural chromosomal mutations) and unidentified multiple congenital abnormalities (indicators of germinal dominant gene and chromosomal mutations). Cases with indicator conditions were selected from the material of the Hungarian Congenital Abnormality Registry. After the diagnostic accuracies were checked, familial and sporadic cases were separated and only the latter group was evaluated for evidence of new mutations. The analysis did not reveal any measurable germinal mutagenic effects of the Chernobyl reactor accident in Hungary. (author)

Mutation breeding in rice in India

Energy Technology Data Exchange (ETDEWEB)

Swaminathan, M S; Siddiq, E A; Singh, C B; Pai, R A [Indian Agricultural Research Institute, New Delhi (India)

1970-03-01

Mutation research was continued in rice with the following aims; (a) to enhance the frequency and spectrum of mutations in indica and japonica rice varieties; (b) to change the grain quality of the japonica variety, Tainan-3, into the indica type; (c) to improve the grain quality of the indica variety, IR-8; (d) to increase the recombination frequency in japonica-indica hybrids. Both nitrosoguanidine and 5-MeV fast neutrons gave a high mutation frequency. The japonica variety was more sensitive to all mutagens than the indica types. Chemical mutagens had no particular advantage over ionizing radiations with reference to either mutation frequency or spectrum. Mutants with indica type of grain occurred readily in Tainan-3 in all treatments. Such mutants had a larger grain length/width ratio and were more resistant to alkali digestion. Fine grain types with better cooking quality occurred in the M{sub 2} populations of IR-8. These mutants are likely to render this high-yielding variety more popular. A wide range of chlorophyll and viable mutations occurred in IR-8 and Tainan-3. Some of these, like those involving dwarfing and slow senescence, are of economic interest, besides those affecting grain quality. Recombination frequency can be influenced in japonica x indica hybrids through the irradiation of F{sub 1} sporocytes. The precise influence varies with the stage at which the plant is irradiated, the dose given and the loci involved. (author)

Somatic mutations in Tradescantia as a model system for studying the effects of the environmental agents

International Nuclear Information System (INIS)

Cebulska-Wasilewska, A.

1986-01-01

The application of the plant model system for studying the biological effects of ionizing radiation and chemical mutagens is presented. The model system is based on the somatic mutation frequency in stamen hair cells of Tradescantia clones heterosygous for flower color. The interaction of chemical mutagens with radiation in the induction of somatic mutations was investigated. The results demonstrate the synergistic interaction between radiation and chemical mutagens like ethyl methanesulfonate and di-bromoethane. The synergistic effect is clearly manifested after combined treatment with radiation and chemicals. In the low dose region the effect depends on the radiation dose and chemical exposure. Other results show the influence of the fluoride treatment on the radiation effect. The fluoride treatment is likely to alter the DNA double strand breaks repair processes. Additionally the usefulness of the model system for studying the mutagenic effectiveness of the pollution in the ambient air is presented. 148 refs. (author)

Mutational pattern of the nurse shark antigen receptor gene (NAR) is similar to that of mammalian Ig genes and to spontaneous mutations in evolution: the translesion synthesis model of somatic hypermutation.

Science.gov (United States)

Diaz, M; Velez, J; Singh, M; Cerny, J; Flajnik, M F

1999-05-01

The pattern of somatic mutations of shark and frog Ig is distinct from somatic hypermutation of Ig in mammals in that there is a bias to mutate GC base pairs and a low frequency of mutations. Previous analysis of the new antigen receptor gene in nurse sharks (NAR), however, revealed no bias to mutate GC base pairs and the frequency of mutation was comparable to that of mammalian IgG. Here, we analyzed 1023 mutations in NAR and found no targeting of the mechanism to any particular nucleotide but did obtain strong evidence for a transition bias and for strand polarity. As seen for all species studied to date, the serine codon AGC/T in NAR was a mutational hotspot. The NAR mutational pattern is most similar to that of mammalian IgG and furthermore both are strikingly akin to mutations acquired during the neutral evolution of nuclear pseudogenes, suggesting that a similar mechanism is at work for both processes. In yeast, most spontaneous mutations are introduced by the translesion synthesis DNA polymerase zeta (REV3) and in various DNA repair-deficient backgrounds transitions were more often REV3-dependent than were transversions. Therefore, we propose a model of somatic hypermutation where DNA polymerase zeta is recruited to the Ig locus. An excess of DNA glycosylases in germinal center reactions may further enhance the mutation frequency by a REV3-dependent mutagenic process known as imbalanced base excision repair.

Biological effects of DNA repair, including mutagenesis. Progress report, June 15, 1980-May 1, 1981

International Nuclear Information System (INIS)

Hutchinson, F.

1981-01-01

A mutagen of interest is used to create mutations in the cI gene of lambda phage, producing a clear plaque phenotype. Genetic mapping is used to determine which restriction fragment in the gene contains the mutation. The fragment is then isolated and sequenced by the Maxam-Gilbert technique. Thus, the actual changes in base sequence produced by the action of the mutagen may be determined and also the base sequence surrounding the mutation. Such studies will be useful in understanding the mechanisms by which a mutation occurs, since any proposed mechanism must be consistent with the observations. The results also give information on the specificity of mutagens

Photobiological activity of 4-methylpsoralen and 4-methyl-4', 5'-dihydropsoralen with respect to lethal and mutagenic effects on E. coli, and prophage induction

Energy Technology Data Exchange (ETDEWEB)

Fujita, H. (Tokai Univ., Isehara, Kanagawa (Japan). School of Medicine)

1984-06-01

The lethal and mutagenic effects on E. coli as well as the induction of prophage lambda were determined after treatment with 4-methylpsoralen, 8-methoxypsoralen, psoralen or 4-methyl-4',5'-dihydropsoralen and UV-A irradiation. All psoralens used caused photokilling and photomutagenesis of strains H/r30R and Hs30R. 4-Methylpsoralen was more efficient for killing and for the induced mutation than 8-methoxypsoralen or psoralen in view of the dose modification factor. This finding can be explained by the methylation effect of psoralen. 4-Methylpsoralen induced more mutation in Hs30R than in H/r30R. Monofunctional 4-methyl-4',5'-dihydropsoralen required much higher fluence than bifunctional psoralens to kill cells and to induce the mutation. When the induced mutation frequency was expressed as a function of survival, mutagenic efficiency ranked in the following order: 8-methoxypsoralen > psoralen > 4-methylpsoralen > 4-methyl-4',5'-dihydropsoralen. 4-Methylpsoralen was 3-4-fold less mutagenic than 8-methoxypsoralen in this plot. Lytic growth of prophage in E. coli AB1157 (lambda) was induced by the treatment. When the bifunctional psoralens were used, the maximum induced fraction was larger than 20%. However, it was only 2% when 4-methyl-4',5'-dihydropsoralen was used.

Mutagenic Organized Recombination Process by Homologous IN vivo Grouping (MORPHING) for directed enzyme evolution.

Science.gov (United States)

Gonzalez-Perez, David; Molina-Espeja, Patricia; Garcia-Ruiz, Eva; Alcalde, Miguel

2014-01-01

Approaches that depend on directed evolution require reliable methods to generate DNA diversity so that mutant libraries can focus on specific target regions. We took advantage of the high frequency of homologous DNA recombination in Saccharomyces cerevisiae to develop a strategy for domain mutagenesis aimed at introducing and in vivo recombining random mutations in defined segments of DNA. Mutagenic Organized Recombination Process by Homologous IN vivo Grouping (MORPHING) is a one-pot random mutagenic method for short protein regions that harnesses the in vivo recombination apparatus of yeast. Using this approach, libraries can be prepared with different mutational loads in DNA segments of less than 30 amino acids so that they can be assembled into the remaining unaltered DNA regions in vivo with high fidelity. As a proof of concept, we present two eukaryotic-ligninolytic enzyme case studies: i) the enhancement of the oxidative stability of a H2O2-sensitive versatile peroxidase by independent evolution of three distinct protein segments (Leu28-Gly57, Leu149-Ala174 and Ile199-Leu268); and ii) the heterologous functional expression of an unspecific peroxygenase by exclusive evolution of its native 43-residue signal sequence.

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)

Mutational specificity of γ-rays

International Nuclear Information System (INIS)

Hoebee, Barbara.

1990-01-01

The aim of the study described in this thesis was to get more information on the mutagenic properties of radiation-induced DNA modifications and the possible mechanisms involved in radiation-induced mutagenesis, principally by investigating the kinds of mutations by DNA sequence analysis. The mutations were analyzed after γ-irradiation of recombinant bacteriophage M13 and plasmide pUC DNA in diluted aqueous solutions, followed by transfection or transformation to E. coli cells, in which the damaged DNA molecules are repaired and replicated. Error-prone repair, misrepair or bypass of lesions during replication may lead to the introduction of mutations. Both the M13 and the plasmid DNA used in our mutation studies contain a mutation target sequence, which makes an easy selection and sequence analysis of mutant DNA molecules possible. Under the radiation conditions used, e.g. irradiation of diluted aqueous DNA solutions, only DNA damage occurs introduced by the water derived OH* and H* radicals and the hydrated electrons. By using different gas conditions during irradiation the relative yields of these reaction species can be manipulated, which opens up the opportunity to determine their effects separately. The mutation spectrum obtained in double-stranded (ds) M13DNA after irradiation under oxic conditions and the mutation spectrum obtained under the same conditions and in the same mutation target but cloned in plasmid DNA, are described. The mutation specificity under anoxic conditions in ds M13DNA is given. Results obtained after irradiation of ds M13DNA under N 2 conditions are discussed together with experiments with single-stranded DNA. Similarities and differences between radiation-induced mutation spectra obtained by other groups and those presented in this thesis are discussed. (author). 155 refs.; 134 figs.; 16 tabs

Safety Evaluation of Turmeric Polysaccharide Extract: Assessment of Mutagenicity and Acute Oral Toxicity

Science.gov (United States)

Velusami, Chandrasekaran Chinampudur; Boddapati, Srinivasa Rao; Hongasandra Srinivasa, Srikanth; Richard, Edwin Jothie; Balasubramanian, Murali

2013-01-01

Curcuma longa Linn. (Zingiberaceae) commonly known as turmeric has long been used for centuries as a spice and household remedy. The present study was carried out to assess the possible mutagenic potential and acute oral toxicity of polysaccharide extract of turmeric rhizome (NR-INF-02) using standard tests. The standard battery of in vitro genotoxicity tests, bacterial reverse mutation test (BRMT), chromosome aberration (CA), and micronucleus (MN) tests were employed to assess the possible mutagenic activity of NR-INF-02 (Turmacin). The results showed no mutagenic effect with NR-INF-02 up to a dose of 5000 µg/mL in BRMT. The results on CA and MN tests revealed the non clastogenic activity of NR-INF-02 in a dose range of 250.36 to 2500 µg/mL with and without metabolic activation (S9). In acute oral toxicity study, NR-INF-02 was found to be safe up to 5 g/kg body weight in Wistar rats. Overall, results indicated that polysaccharide extract of C. longa was found to be genotoxically safe and also exhibited maximum tolerable dose of more than 5 g/kg rat body weight. PMID:24455673

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

Lack of chemically induced mutation in repair-deficient mutants of yeast

International Nuclear Information System (INIS)

Prakash, L.

1974-01-01

Two genes, rad6 and rad9, that confer radiation sensitivity in the yeast Saccharomyces cerevisiae also greatly reduce the frequency of chemically-induced reversions of a tester mutant cyc1-131, which is a chain initiation mutant in the structural gene determining iso-1-cytochrome c. Mutations induced by ethyl methanesulfonate (EMS), diethyl sulfate (DES), methyl methanesulfonate (MMS), dimethyl sulfate (DMS), nitroquinoline oxide (NQO), nitrosoguanidine (NTG), nitrogen mustard (HN2), β-propiolactone, and tritiated uridine, as well as mutations induced by ultraviolet light (UV) and ionizing radiation were greatly diminished in strains homozygous for either the rad6 or rad9 gene. Nitrous acid and nitrosoimidazolidone (NIL), on the other hand, were highly mutagenic in these repair-deficient mutants, and at low doses, these mutagens acted with about the same efficiency as in the normal RAD strain. At high doses of either nitrous acid or NIL, however, reversion frequencies were significantly reduced in the two rad mutants compared to normal strains. Although both rad mutants are immutable to about the same extent, the rad9 strains tend to be less sensitive to the lethal effect of chemical mutagens than rad6 strains. It is concluded that yeast requires a functional repair system for mutation induction by chemical agents. (auth)

Lack of chemically induced mutation in repair-deficient mutants of yeast.

Science.gov (United States)

Prakash, L

1974-12-01

Two genes, rad6 and rad9, that confer radiation sensitivity in the yeast Saccharomyces cerevisiae also greatly reduce the frequency of chemically-induced reversions of a tester mutant cyc1-131, which is a chain initiation mutant in the structural gene determining iso-1-cytochrome c. Mutations induced by ethyl methanesulfonate (EMS), diethyl sulfate (DES), methyl methanesulfonate (MMS), dimethyl sulfate (DMS), nitroquinoline oxide (NQO), nitrosoguanidine (NTG), nitrogen mustard (HN2), beta-propiolactone, and tritiated uridine, as well as mutations induced by ultraviolet light (UV) and ionizing radiation were greatly diminished in strains homozygous for either the rad6 or rad9 gene. Nitrous acid and nitrosoimidazolidone (NIL), on the other hand, were highly mutagenic in these repair-deficient mutants, and at low doses, these mutagens acted with about the same efficiency as in the normal RAD strain. At high doses of either nitrous acid or NIL, however, reversion frequencies were significantly reduced in the two rad mutants compared to normal strains. Although both rad mutants are immutable to about the same extent, the rad9 strains tend to be less sensitive to the lethal effect of chemical mutagens than rad6 strains. It is concluded that yeast requires a functional repair system for mutation induction by chemical agents.

A set of lacZ mutations in Escherichia coli that allow rapid detection of each of the six base substitutions

International Nuclear Information System (INIS)

Cupples, C.G.; Miller, J.H.

1989-01-01

We describe the construction of six strains of Escherichia coli with different mutations at the same coding position in the lacZ gene, which specifies the active site glutamic acid residue at position 461 in beta'-galactosidase. Each strain is Lac- and reverts to Lac+ only by restoring the glutamic acid codon. The strains have been designed so that each reverts via one of the six base substitutions. The set of strains allows detection of each transition and transversion simply by monitoring the Lac- to Lac+ frequency, as demonstrated here with characterized mutagens and mutator alleles. These strains are useful for rapidly determining the mutagenic specificity of mutagens at a single site, for detecting low levels of stimulation of certain base substitutions, for monitoring specific base changes in response to various experimental conditions or strain backgrounds, and for isolating new mutator strains

Studies on mutation breeding in sweet potato (Ipomoea batatas (L.) Lam.)

International Nuclear Information System (INIS)

Kukimura, H.; Kouyama, Y.

1982-01-01

Different genotypes were subjected to gamma rays and EMS to examine the effects on tuber skin colour mutation. Different mutation rates were obtained according to the genotypes. The gamma irradiation induced larger sector size of skin colour mutation than EMS. Gamma rays had an effect on inducing flowering in MV 1 which is utilized in cross breeding. Mutagenic treatment by gamma rays and EMS on the hybrid true seed which segregates in a Mendelian ratio for pigmentation in leaf, stem and tuber and for shape of leaf gave some bias to their segregation ratios. Effects of gamma-ray irradiation on quantitative characters, such as dry matter content and total sugar content in tubers, were also investigated in hybrid populations. The treatments enlarged genetic variations on both the characters, being more effective on total sugar content. Clonal progenies derived from mutagenic treatment by gamma rays and EI were investigated for their quantitative MV 4 -MV 6 characters (tuber yield, dry matter content and total sugar content) in MV 4 -MV 6 . Heritabilities in a broad sense and phenotypic variances were estimated from the measurements on derivative strains obtained by random selection from mutagenic treatment plots. Artificial selection was effective only for tuber yield. Mutant clones with short stem length decreased their tuber yield and vice versa. A few mutant clones were found to excel the originals in dry matter content and total sugar content. Some aspects of mutation breeding in sweet potato are also discussed

Mutation of Haemophilus influenzae transforming DNA in vitro with near-ultraviolet radiation: action spectrum

Energy Technology Data Exchange (ETDEWEB)

Cabrera-Juarez, E; Setlow, J K [Escuela Nacional de Ciencias Biologicas, Mexico City. Dept. de Bioquimica; Oak Ridge National Lab., Tenn. (USA). Biology Div.)

1976-05-01

Mutations were produced in purified transforming DNA from Haemophilus influenzae by near UV radiation and were assayed as mutants among cells transformed with irradiated DNA. The maximum efficiency of mutation induction was at around 334 nm, and the efficiency dropped off steeply at lower and higher wavelengths. The difference between the action spectrum for mutation and that for the oxygen-independent inactivation of transforming DNA, which had a shoulder at 365 nm, indicates that there are different lesions involved in the inactivating and mutagenic effects of near-UV. The presence of histidine during irradiation enhanced the mutagenic effect at 334 and 365 nm, although it protected against inactivation at 365 nm. The effective near-UV wavelengths for in vitro mutation are to some extent the same as the effective wavelengths for mutation in vivo reported previously. These findings indicate that mutations are produced in vivo by near-UV with DNA as the primary target molecule rather than by a secondary non-photochemical reaction between DNA and some other cell component.

Mutagenic action of radiation with different LET on Bacillus subtilis cells

International Nuclear Information System (INIS)

Borejko, A.V.; Krasavin, E.A.

1996-01-01

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) dependence on the mutagenic assay is shifted at the low region of LET. (author). 11 refs., 4 figs

Intragenic FMR1 disease-causing variants: a significant mutational mechanism leading to Fragile-X syndrome

Science.gov (United States)

Quartier, Angélique; Poquet, Hélène; Gilbert-Dussardier, Brigitte; Rossi, Massimiliano; Casteleyn, Anne-Sophie; Portes, Vincent des; Feger, Claire; Nourisson, Elsa; Kuentz, Paul; Redin, Claire; Thevenon, Julien; Mosca-Boidron, Anne-Laure; Callier, Patrick; Muller, Jean; Lesca, Gaetan; Huet, Frédéric; Geoffroy, Véronique; El Chehadeh, Salima; Jung, Matthieu; Trojak, Benoit; Le Gras, Stéphanie; Lehalle, Daphné; Jost, Bernard; Maury, Stéphanie; Masurel, Alice; Edery, Patrick; Thauvin-Robinet, Christel; Gérard, Bénédicte; Mandel, Jean-Louis; Faivre, Laurence; Piton, Amélie

2017-01-01

Fragile-X syndrome (FXS) is a frequent genetic form of intellectual disability (ID). The main recurrent mutagenic mechanism causing FXS is the expansion of a CGG repeat sequence in the 5′-UTR of the FMR1 gene, therefore, routinely tested in ID patients. We report here three FMR1 intragenic pathogenic variants not affecting this sequence, identified using high-throughput sequencing (HTS): a previously reported hemizygous deletion encompassing the last exon of FMR1, too small to be detected by array-CGH and inducing decreased expression of a truncated form of FMRP protein, in three brothers with ID (family 1) and two splice variants in boys with sporadic ID: a de novo variant c.990+1G>A (family 2) and a maternally inherited c.420-8A>G variant (family 3). After clinical reevaluation, the five patients presented features consistent with FXS (mean Hagerman's scores=15). We conducted a systematic review of all rare non-synonymous variants previously reported in FMR1 in ID patients and showed that six of them are convincing pathogenic variants. This study suggests that intragenic FMR1 variants, although much less frequent than CGG expansions, are a significant mutational mechanism leading to FXS and demonstrates the interest of HTS approaches to detect them in ID patients with a negative standard work-up. PMID:28176767

Use of induced mutations for potato improvement

International Nuclear Information System (INIS)

Kishore, H.; Das, B.; Subramanyam, K.N.; Chandra, R.; Upadhya, M.D.

1975-01-01

The investigations aim at the utilization of induced mutations for potato improvement. The effect of γ-rays was tested on selfed seeds and hybrid seeds as well as on tubers of several potato varieties. Chemical mutagens have been successfully employed to produce daylength neutral clones. An attempt to induce resistance against Pseudomonas solanacearum did not give conclusive results. Potato improvement in relation of yield and other characters of economic significance like maturity and attributes of tubers has been handicapped by several technical considerations world over. The crux of the problem lies in the narrow genetic base (variability) for potato breeders to work with. The use of mutation breeding, therefore, offers a good tool for this. Improvement by mutation breeding for the quantitative characters besides the resistance to disease and pest has been demonstrated in other crops like white mustard variety Primex (Anderson and Olsson, 1954), barley (Gustafsson, 1965) and peanut (Gregory, 1956). Keeping these in view and the success we had in isolating photoperiod insensitive types (Upadhaya et al, 1973, 1974) study was enlarged to use mutagens to increase as wide a spectrum as possible of the variability for quantative and qualitative characters. (author)

Mutagenic effect of gamma-rays on improvement of yield attributing traits of greengram (Vigna radiata (L.) Wilczek)

International Nuclear Information System (INIS)

Das, T.R.; Baisakh, B.

2014-01-01

Seed samples of two morphologically distinct varieties (Sujata and OBGG-52) of greengram were treated with three doses of Gamma-rays (200 Gy, 400 Gy and 600 Gy). Mutagenic treatments in general showed reduction in mean values of germination, survival and plant growth traits in comparison to control in M 1 generation and the magnitude of reduction was directly related to the dose of the mutagens. The spectrum of chlorophyll mutations includes albina, xantha, chlorina, striata and viridis in both the varieties. The varied morphological mutations observed in leaf of both the genotypes were tricotyledonary, quadrifoliate, pentafoliate and lobed leaf. Early flowering, late flowering, tall plant, trailing type, profused poded, bold poded and sterile plant were also observed as an effect of mutagen in both the genotypes. The M 2 populations showed wider range of variations than the parent varieties. Magnitude of changes varied with mutagen dose and the varieties. Higher the dose of treatment, greater the shift in the mean and variance of different yield parameters. Genetic advance estimates showed that selection in M 2 populations would be effective in improving the yield/plant. Following selection among M 2 plants and M 3 progenies on the basis of higher yield, high yielding mutant cultures in both varieties were isolated in M 4 and evaluated in M 5 generation. Gamma-ray dose of 200 Gy was most effective for improving the yield traits in both the genotypes as it brought out improvement in pods/plant, pod length and 100-seed wt. where as 400 Gy improved 100- seed wt. in only Sujata and 600 Gy improved pod length and seeds/pod only. Isolation of high yielding lines from the gamma-rays treated population of greengram proved that different doses of gamma rays induced improvement of different yield attributing characters in greengram. (author)

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

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

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.

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.)

Oncogenesis of melanoma B16 cell clones mutagenized by space environment

International Nuclear Information System (INIS)

Guo Yupeng; Yang Hongsheng; Tang Jingtian; Xu Mei; Geng Chuanying; Fang Qing; Xu Bo; Li Hongyan; Xiang Xing; Pan Lin

2005-01-01

Objective: To explore the oncogenesis of the melanoma B16 cell clones mutagenized by space environment, and find the B16 cell clones with remarkably mutated immunogenicity. Methods: B16 cells were carried by the Chinese 20th recoverable satellite to the outer space, and were harvested after 18 days' spaceflight and then monocloned. Four cell clones, which were randomly selected from the total 110 clones obtained , and the control clone were routinely cultured. The cultured cells were injected to 10 groups of C57BL/6J mice, 82.1 mice in each group. Five groups of mice received hypodermic injection and another 5 groups of mice received abdominal injection. The survival time was observed in abdominal injection groups. The mice in hypodermic injection groups were sacrificed after 14 days, the tumor, spleen and thymus were weighted, and the serum IL-2 concentration was determined. Moreover, the melanoma tumor tissues were examined histopathologically. Results: An experiment program suitable to screening space mutagenesis of B16 tumor cell clones in vivo and the observation indices were basically established. One clone was found out which was remarkably different from the control clone in latent period of tumor formation, tumor weight, survival time of the tumor-bearing mice and the expression of IL-2. Conclusions: Cultured melanoma B16 cells could be mutated by outer space environment. The further study will be focused on the influence of space environment on immunogenicity of mutagenized B16 cells. (authors)

Toxicity, mutagenicity and transport in Saccharomyces cerevisiae of three popular DNA intercalating fluorescent dyes.

Science.gov (United States)

Sayas, Enric; García-López, Federico; Serrano, Ramón

2015-09-01

We have compared the toxicity, mutagenicity and transport in Saccharomyces cerevisiae of three DNA-intercalating fluorescent dyes widely used to stain DNA in gels. Safety data about ethidium bromide (EtBr) are contradictory, and two compounds of undisclosed structure (Redsafe and Gelred) have been proposed as safe alternatives. Our results indicate that all three compounds inhibit yeast growth, with Gelred being the most inhibitory and also the only one causing cell death. EtBr and Gelred, but not Redsafe, induce massive formation of petite (non-respiratory) mutants, but only EtBr induces massive loss of mitochondrial DNA. All three compounds increase reversion of a chromosomal point mutation (lys2-801(amber) ), with Gelred being the most mutagenic and Redsafe the least. These dyes are all cationic and are probably taken by cells through non-selective cation channels. We could measure the glucose-energized transport of EtBr and Gelred inside the cells, while uptake of Redsafe was below our detection limit. We conclude that although all three compounds are toxic and mutagenic in the yeast system, Redsafe is the safest for yeast, probably because of very limited uptake by these cells. Copyright © 2015 John Wiley & Sons, Ltd.

Induced mutations for improvement of grain legume production II

International Nuclear Information System (INIS)

1982-02-01

Out of 18 papers presented, 15 fall within the INIS subject scope. Other topics covered were: mutagenic efficiency of ethylmethane sulphonate in soybean; induced mutations for rust resistance in soybean; and nitrogen fixation-potentials for improvement in legumes

Induced plasmon mutations affecting the growth habit of peanuts, A. hypogaea L

International Nuclear Information System (INIS)

Levy, A.; Ashri, A.

1978-01-01

The effectiveness of the acridines ethidium bromide (EB) and acriflavine in inducing plasmon mutations was compared with the alkylating agents ethyl methanesulphonate (EMS) and diethyl sulphate and to γ-rays. The growth habit (trailing versus bunch) of peanuts (A. hypogaea), controlled by genic-cytoplasmic interactions, was utilized. Breeding tests distinguishing nuclear from plasmon mutations were developed and are described in detail. Plasmon mutations were induced, but there were differences in mutation yields between the cultivars and the mutagens. (Auth.)

Cytotoxic, phytotoxic, and mutagenic appraisal to ascertain toxicological potential of particulate matter emitted from automobiles.

Science.gov (United States)

Anwar, Khaleeq; Ejaz, Sohail; Ashraf, Muhammad; Altaf, Imran; Anjum, Aftab Ahmad

2013-07-01

Vehicular air pollution is a mounting health issue of the modern age, particularly in urban populations of the developing nations. Auto-rickshaws are not considered eco-friendly as to their inefficient engines producing large amount of particulate matter (PM), thus posing significant environmental threat. The present study was conducted to ascertain the cytotoxic, phytotoxic, and mutagenic potential of PM from gasoline-powered two-stroke auto-rickshaws (TSA) and compressed natural gas-powered four-stroke auto-rickshaws (FSA). Based on the increased amount of aluminum quantified during proton-induced X-ray emission analysis of PM from TSA and FSA, different concentrations of aluminum sulfate were also tested to determine its eco-toxicological potential. The MTT assay demonstrated significant (p < 0.001) dose-dependent cytotoxic effects of different concentrations of TSA, FSA, and aluminum sulfate on BHK-21 cell line. LC50 of TSA, FSA, and aluminum sulfate was quantified at 16, 11, and 23.8 μg/ml, respectively, establishing PM from FSA, a highly cytotoxic material. In case of phytotoxicity screening using Zea mays, the results demonstrated that all three tested materials were equally phytotoxic at higher concentrations producing significant reduction (p < 0.001) in seed germination. Aluminum sulfate proved to be a highly phytotoxic agent even at its lowest concentration. Mutagenicity was assessed by fluctuation Salmonella reverse mutation assay adopting TA100 and TA98 mutant strains with (+S9) and without (-S9) metabolic activation. Despite the fact that different concentrations of PM from both sources, i.e., TSA and FSA were highly mutagenic (p < 0.001) even at lower concentrations, the mutagenic index was higher in TSA. Data advocate that all tested materials are equally ecotoxic, and if the existing trend of atmospheric pollution by auto-rickshaws is continued, airborne heavy metals will seriously affect the normal growth of local inhabitants and

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)

Determination of residual 4'-aminomethyl-4,5',8-trimethylpsoralen and mutagenicity testing following psoralen plus UVA treatment of platelet suspensions

International Nuclear Information System (INIS)

Wagner, S.J.; Robinette, D.; Dodd, R.Y.; White, R.; Wolf, L.; Chapman, J.; Lawlor, T.E.

1993-01-01

Psoralens and UVa light have been used in the laboratory to study the inactivation of viruses that may be infrequently present in platelet concentrates prepared for transfusion. In order to evaluate safety aspects of the treatment of platelet suspensions with 4'-aminomethyl-4,5'8-trimethylpsoralen (AMT), the authors have investigated the residual levels and mutagenic potential of AMT after UVA phototreatment. The results suggest that residual available AMT is mutagenic in the AMES test and that the observed frameshift mutations may be caused by binding of AMt or its metabolites to nucleic acids in the absence of UVA light. (Author)

The mutation studies of mutagen-sensitive and DNA repair mutants of Chinese hamster fibroblasts

International Nuclear Information System (INIS)

Schultz, R.A.; Chang, C.C.; Trosko, J.E.

1981-01-01

We have previously reported the isolation and partial characterization of DNA repair and/or mutagen-sensitive mutant Chinese hamster cell strains. Here we present the results of a detailed study of the ultraviolet light (UV)-induced mutability of one of these strains, UVs-7, and provide preliminary mutability data on two additional lines, UVr-23 and UVs-40. UVs-7 in extremely deficient in unscheduled DNA synthesis (UDS) but only slightly more sensitive to UV than the parental line. When examined for the UV-inducibility of mutants resistant to ouabain, 6-thioguanine, or diphtheria toxin, UVs-7 was found to be hypermutable at all three loci as compared to the parental line. The degree of hypermutability was not the same for any two loci. UVs-40, a highly UV-sensitive strain, was also found to be hypermutable at the ouabain-resistant (ouar) locus. UVr-23, which is UV-resistant and more proficient at UDS than the parental line, appeared to exhibit a tendency toward hypomutability at both the ouabain(ouar) and 6-thioguanine--resistant (6TGr) loci. Further characterization of all these lines should aid in delineating mammalian mechanisms of DNA repair and mutagenesis

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.

Mutagenic potency of MMS-induced 1meA/3meC lesions in E. coli.

Science.gov (United States)

Nieminuszczy, Jadwiga; Mielecki, Damian; Sikora, Anna; Wrzesiński, Michał; Chojnacka, Aleksandra; Krwawicz, Joanna; Janion, Celina; Grzesiuk, Elzbieta

2009-12-01

The mutagenic activity of MMS in E. coli depends on the susceptibility of DNA bases to methylation and their repair by cellular defense systems. Among the lesions in methylated DNA is 1meA/3meC, which is recently recognized as being mutagenic. In this report, special attention is focused on the mutagenic properties of 1meA/3meC which, by the activity of AlkB-dioxygenase, are quickly and efficiently converted to natural A/C bases in the DNA of E. coli alkB(+) strains, preventing 1meA/3meC-induced mutations. We have found that in the absence of AlkB-mediated repair, MMS treatment results in an increased frequency of four types of base substitutions: GC-->CG, GC-->TA, AT-->CG, and AT-->TA, whereas overproduction of PolV in CC101-106 alkB(-)/pRW134 strains leads to a markedly elevated level of GC-->TA, GC-->CG, and AT-->TA transversions. It has been observed that in the case of AB1157 alkB(-) strains, the MMS-induced and 1meA/3meC-dependent argE3-->Arg(+) reversion occurs efficiently, whereas lacZ(-)--> Lac(+) reversion in a set of CC101-106 alkB(-) strains occurs with much lower frequency. We considered several reasons for this discrepancy, namely, the possible variance in the level of the PolV activity, the effect of the PolIV contents that is higher in CC101-106 than in AB1157 strains and the different genetic cell backgrounds in CC101-106 alkB(-) and AB1157 alkB(-) strains, respectively. We postulate that the difference in the number of targets undergoing mutation and different reactivity of MMS with ssDNA and dsDNA are responsible for the high (argE3-->Arg(+)) and low (lacZ(-) --> Lac(+)) frequency of MMS-induced mutations.

Mutations induced by ultraviolet light

International Nuclear Information System (INIS)

Pfeifer, Gerd P.; You, Young-Hyun; Besaratinia, Ahmad

2005-01-01

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

Whole genome sequencing of mutation accumulation lines reveals a low mutation rate in the social amoeba Dictyostelium discoideum.

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Gerda Saxer

Full Text Available Spontaneous mutations play a central role in evolution. Despite their importance, mutation rates are some of the most elusive parameters to measure in evolutionary biology. The combination of mutation accumulation (MA experiments and whole-genome sequencing now makes it possible to estimate mutation rates by directly observing new mutations at the molecular level across the whole genome. We performed an MA experiment with the social amoeba Dictyostelium discoideum and sequenced the genomes of three randomly chosen lines using high-throughput sequencing to estimate the spontaneous mutation rate in this model organism. The mitochondrial mutation rate of 6.76×10(-9, with a Poisson confidence interval of 4.1×10(-9 - 9.5×10(-9, per nucleotide per generation is slightly lower than estimates for other taxa. The mutation rate estimate for the nuclear DNA of 2.9×10(-11, with a Poisson confidence interval ranging from 7.4×10(-13 to 1.6×10(-10, is the lowest reported for any eukaryote. These results are consistent with low microsatellite mutation rates previously observed in D. discoideum and low levels of genetic variation observed in wild D. discoideum populations. In addition, D. discoideum has been shown to be quite resistant to DNA damage, which suggests an efficient DNA-repair mechanism that could be an adaptation to life in soil and frequent exposure to intracellular and extracellular mutagenic compounds. The social aspect of the life cycle of D. discoideum and a large portion of the genome under relaxed selection during vegetative growth could also select for a low mutation rate. This hypothesis is supported by a significantly lower mutation rate per cell division in multicellular eukaryotes compared with unicellular eukaryotes.

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

Mutagenic effectiveness and efficiency of EMS, DES and gamma-rays in rice

International Nuclear Information System (INIS)

Kaul, M.L.H.; Bhan, A.K.

1977-01-01

Data on chlorophyll mutation frequency after treatment with EMS, DES and gamma-rays and sequential administration of gamma-rays and the two alkylating agents in three varieties of rice have been used to work out quantitatively the effectiveness and efficiency of each mutagen and combination treatment. For effectiveness, the order is EMS > DES and for efficiency it is EMS > DES > gamma-rays. In some sequential treatments (Gamma-rays + DES in 'IR8' and 'Basmati'; DES + gamma-rays in 'IR8' and 'Jhona'; Gamma-rays + EMS in 'IR8' and 'Basmati'; and EMS + gamma-rays in 'IR8', 'Jhona' and 'Basmati') mutation frequency is more than additive (synergistic) but these treatments are decisively less efficient because of their relatively high injurious effects in the M 1 generation. EMS induces more albinas than gamma-rays do. The mutational spectrum patterns induced by gamma-rays and DES are alike. In general, combination treatments tend to increase the frequency of albinas over other types of chlorophyll mutants. (orig.) [de

Effects of the umuC36 mutation on ultraviolet-radiation-induced base-change and frameshift mutations in Escherichia coli

International Nuclear Information System (INIS)

Kato, T.; Nakano, E.

1981-01-01

The effects of the umuC36 mutation on the induction of base-change and frameshift mutations were studied. An active umuC gene was necessary in either the uvr + or uvr - strains of Escherichia coli K12 for UV- and X-ray-induced mutations to His + , ColE and Spc, which are presumably base-change mutations, but it was not essential for ethyl methanesulphonate or N-methyl-N'-nitro-N-nitrosoguanidine-induced His + mutations. In contrast, only 1 out of 13 trp - frameshift mutations examined was UV reversible, and the process of mutagenesis was umuC + -dependent, whereas a potent frameshift mutagen, ICR191, effectively induced Trp + mutations in most of the strains regardless of the umu + or umuC genetic background. These results suggest that base substitutions are a major mutational type derived from the umuC + -dependent pathway of error-prone repair. (orig.)

Morphological mutations induced by gamma rays, ethylene imine and N-nitroso-N-ethyl urea in lentil (Lens culinaris medik.)

International Nuclear Information System (INIS)

Solanki, I.S.; Sharma, B.

2003-01-01

Dry and healthy seeds of a large seeded lentil cv, 'Precoz Selection', were treated with three doses each of gamma rays, ethylene imine (EI) and N-nitroso-N-ethyl urea (NEU). Based on the frequency of morphological mutations, the mutagens were arranged in the order: NEU > EI >. Gamma rays and dose-dependent relationship was observed in the case of gamma rays (5 kR 1 damage groups induced morphological mutations in the order: HH > HL > LH > LL. The morphological mutations included changes for growth habit, foliage, plant height and maturity and flowering behaviour. A mild relative mutagenic specificity and differences in mutability of genes for different traits were observed, In general the spectrum of morphological mutations was not influenced by the groups of M 1 damage, except that some mutation types occurred more frequently, than others in certain groups. (author)

Characterization of carbon ion-induced mutations in Arabidopsis thaliana

International Nuclear Information System (INIS)

Shikazono, N.; Suzuki, C.; Kitamura, S.; Watanabe, H.; Tano, S.; Tanaka, A.

2003-01-01

Full text: Irradiation of Arabidopsis thaliana by carbon ions was carried out to investigate the mutational effect of ion particles in higher plants. The averaged mutation rate of carbon ions was 2.0 X 10 -6 / Gy, which was 18-fold higher than that of electrons. PCR analysis of the carbon ion-induced mutants showed that, out of 28 mutant alleles, 14 had point-like mutations within the gene, while 14 contained large structural alterations. In the case of 12 electron-induced mutants, 9 had point-like mutations within the gene, while 3 contained large structural alterations. These results suggest that carbon ions are more likely to induce large structural alterations compared with electrons. Further sequence analysis revealed that most of the point-like mutations induced by carbon ions were short deletions. In the case of rearrangements, DNA strand breaks were found to be rejoined using, if present, short homologous sequences for both types of radiation. After carbon ion-irradiation, small deletions were frequently observed around the breakpoints, whereas duplications of terminal sequence were found after electron-irradiation. These results suggest that non-homologous end joining (NHEJ) pathway operates after plant cells are exposed to both ion particles and electrons but that different mode of rejoining deals with the broken ends produced by each radiation. From the present results, it seems reasonable to assume that carbon ions could predominantly induce null mutations in Arabidopsis. The fact that the molecular nature of carbon ion-induced mutation was different from that of electrons and that the molecular mechanisms of cells to induce mutations appeared to be also different implicates that ion particle is not only valuable as a new mutagen but also useful as a new tool to study repair mechanisms of certain types of DNA damage

Effect of tumor promoters on ultraviolet light-induced mutation and mitotic recombination in Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Kunz, B.A.; Hannan, M.A.; Haynes, R.H.

1980-01-01

Recently, it has been suggested that mitotic recombination is involved in tumor promotion. On this basis, one might expect tumor promoters to be recombinagenic. D7 is a diploid strain of yeast in which both mutation and mitotic recombination can be measured. We have used this strain to assay the known tumor promoters, iodacetate, anthralin, and 12-0-tetradecanoylphorbol-13-acetate, and the cocarcinogen, catechol, for mutagenicity, recombinagenicity, and the ability to enhance ultraviolet light (UV)-induced genetic events. In the absence of preirradiation with UV, iodoacetate was found to be recombinagenic whereas catechol was mutagenic; however, in both cases, the effects were small. Iodoacetate, anthralin, and catechol potentiated UV-induced mitotic crossing-over, aberrant colony formation, and mutation, while catechol also increased UV-induced gene conversion. We were unable to detect any mutagenic or recombinagenic effect of 12-0-tetradecanoyl-phorbol-13-acetate in either whole cells or spheroplasts. Our results do not indicate any consistent correlation between tumor-promoting activity and the ability of an agent to induce mitotic recombination in yeast. However, the ability to potentiate UV-induced mutation and mitotic recombination may reflect the cocarcinogenic activity of certain promoters

Cytotoxic and mutagenic effects of specific carcinogen-DNA adducts in diploid human fibroblasts

International Nuclear Information System (INIS)

McCormick, J.J.; Maher, V.M.

1985-01-01

A comparison of the cytotoxicity and mutagenicity of a series of carcinogens in normal diploid human fibroblasts and in cells deficient in one or more DNA repair processes has provided insight into the specific DNA adduct(s) responsible for these biological effects. The carcinogens tested include ultraviolet radiation; reactive derivatives of structurally related aromatic amides; metabolites of benzo(a)pyrene; the simple alkylating agents N-methyl-N'-nitro-N-nitrosoguanidine and N-ethyl-N-nitrosourea; and aflatoxin B 1 dichloride, a model for the reactive 2,3-epoxide of aflatoxin B 1 . Exponentially growing cells were exposed to agents and assayed for mutations and cell killing. Cells deficient in repair of particular DNA adducts or lesions proved more sensitive to the agent causing those lesions than did normally repairing cells. Many of the carcinogens were compared for their mutagenic and/or cytotoxic effect, not only as a function of dose administered, but also as a function of the initial number of adducts or photoproducts induced in DNA and the number remaining at critical times posttreatment. The results demonstrated a high correlation between the number of DNA lesions remaining unexcised at the time the DNA was replicated and frequency of mutations induced. Comparative studies of the frequency of UV-induced transformation of normal and repair-deficient cells showed this also to be true for transformation

Biological effects of dyes on bacteria. VI. Mutation induction by acridine orange and methylene blue in the dark with special reference to Escherichia coli WP6 (polA1)

Energy Technology Data Exchange (ETDEWEB)

Webb, R.B.; Hass, B.S.

1984-01-01

Acridine orange (AO) and methylene blue (MB) in the dark were shown to be weak to moderate mutagens (induction of resistance to T5 phage) in repair-deficient strains of Escherichia coli B/r. However, strain WP2, (wild-type) was not mutated by AO in the dark, in confirmation of earlier data. The presence of 2 ..mu..M AO reduced by 41% the spontaneous mutation rate in strain WP2, from 4.1 to 2.4 mutants/10/sup 8/ cells/generation. In the polymerase I-deficient strain WP6 (polA1), 2 ..mu..M AO increased the mutation rate in the dark 14-fold. It is proposed that both spontaneous and AO-induced mutagenesis in the absence of light occur at the site of semiconservative DNA replication. If the intercalation mechanism for the effects in the absence of light is valid, the wild-type strain (WP2) may be resistant to frameshift mutagenesis induced by intercalated compounds, while the polymerase I-deficient strain (WP6) may be highly susceptible to the presence of an intercalated dye such as AO at the DNA-replication fork. MB and AO likely act through different mechanisms since MB is only a moderate mutagen in strain WP6 and the other repair-deficient strains tested.

Intramolecular tautomerisation and the conformational variability of some classical mutagens – cytosine derivatives: quantum chemical study

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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

Mutagenic effect of sewage waters of the Ignalina NPP on the cells of sea-trout

International Nuclear Information System (INIS)

Stasiunaite, P.

1996-01-01

Using a developing embryos of sea-trout as a test-object, the mutagenicity of water in the first biotope of Lake Drukshiai as well as in industrial and rain water sewer pipe was evaluated. Artesian water was used as a control one. The mutagenic potential of water in station 1 of Lake Drukshiai approximately made up 8.1% and statistically did not differ from the control (7.0%). The effect of water of station 7 upon the inherited embryonic cells was significantly greater, average frequency of chromosome aberration reaching 27.3%. The analysis of the obtained data showed that industrial - rain sewage water constantly penetrating into Lake Drukshiai may significantly worsen its ecological situation, i.e. to increase the accumulation of mutations in the communities and their amount in the succeeding generations. The genotoxicity of water of the 1 st biotope of Lake Drukshiai, which is the farthest point from the Ignalina NPP, may be used as a control when investigating the mutagenic impact of water of other biotopes in the lake, especially in the stations located at the shortest distance from the energetic objects. 8 refs., 1 tab

Distinguishing potential sources of genotoxic exposure via HPRT mutations

International Nuclear Information System (INIS)

Molholt, B.; Finette, B.A.

2000-01-01

T-cell HPRT (hypoxanthine phosphoribosyltransferase) mutations were used to monitor to environmental mutagens in children who have developed cancer at a persistently high rate in Toms River, New Jersey, USA. A preliminary epidemiological study has found a statistically-significant association between drinking public water (by pregnant mother or infant) and subsequent risk for childhood cancer. Three potential sources of mutagenic exposures in Toms River may have increased the rate of carcinogenic initiation significantly in children: 1. Benzidine-based, other azo-dye and anthraquinone dye wastes released by Ciba-Geigy enterprise; 2. Plastic wastes of Union Carbide enterprise; 3. Radium-224, present in unusually high concentrations in the Cohansey aquifer. Specific patterns of HPRT mutations are utilized to distinguish these various potential sources of carcinogenic exposures in the drinking water of families with childhood cancer and to differentiate chemically or radiologically induced cancers from those which occur spontaneously [ru

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

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

Plant mutation breeding and application of isotopic tracer in Chinese agriculture

International Nuclear Information System (INIS)

Liang Qu

1993-03-01

The progress and achievements made in plant mutation breeding and application of isotopic tracer in Chinese agriculture are outlined. Plant mutation breeding is well developed not only in improvement of crops but also in methodology of mutation induction. More than 325 mutant varieties and hundreds of various valuable mutants of 29 different species have been obtained. The mutant cultivars released have covered more than 10 million hectares in total area. The systematic studies on methodology such as techniques for mutagenic treatment, development of various mutagens, screening and selecting techniques of mutation etc. have been carried out in China. The techniques of radioisotopic tracer used in many research fields are described. Application of isotopic tracer in studies of fertilization and plant nutrition, environment protection, nitrogen-fixation, animal production and diagnosis of diseases, and so on, have made great achievements and benefits in China. Many kinds of labelled compounds, especially of labelled agro-chemicals have been synthesized in the Institute for Application of Atomic Energy (IAAE). Chinese Academy of Agricultural Sciences (CAAS). The proposals for the region cooperation in Asia on application of atomic energy in agriculture are included

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.

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.

Induced mutations for improvement of grain legume production

International Nuclear Information System (INIS)

1980-11-01

After an introduction on plant science research in Malaysia concerning crop breeding, 22 research reports are presented, 17 of which are analyzed individually and constitute separate INIS references. The remaining 5 were essentially concerned with only future applications of nuclear technology: a paper by V.L. Chopra (India) on mutation breeding for partial disease resistance of wheat; by H.H. Hoppe (Federal Republic of Germany) on mechanisms of resistance against Uromyces in Phaseolus vulgaris; by I.S. Santos (Philippines) on induction evaluation and utilization of beneficial mutations in the winged bean (Psophocarpus tetragonolobus), where gamma rays and fast neutrons will be used as well as other mutagens; by F. Saccardo (Italy) on breeding for disease resistance in peas and other vegetables (short communication only); and by E. Balazs and I. Sziraki (Hungary) on in vitro studies on virus resistance of legumes, including virus-host interaction studies involving gamma irradiation (short communication only). The conclusions and recommendations of the Regional Seminar on Induced Mutations for the Improvement of Grain Legumes in S.E. Asia 1975 (IAEA-203, 1977) were considered and generally endorsed, with some clarification. Conclusions and recommendations are given on p.121-126

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.

Determination of residual 4'-aminomethyl-4,5',8-trimethylpsoralen and mutagenicity testing following psoralen plus UVA treatment of platelet suspensions

Energy Technology Data Exchange (ETDEWEB)

Wagner, S.J.; Robinette, D.; Dodd, R.Y. (American Red Cross Blood Services, Rockville, MD (United States). Jerome H. Holland Lab. for Biomedical Sciences); White, R.; Wolf, L.; Chapman, J. (Baxter Biotech, Round Lake, IL (United States). Fenwal Labs.); Lawlor, T.E. (Hazleton Labs., Vienna, VA (United States). Molecular and Cellular Toxicology)

1993-05-01

Psoralens and UVa light have been used in the laboratory to study the inactivation of viruses that may be infrequently present in platelet concentrates prepared for transfusion. In order to evaluate safety aspects of the treatment of platelet suspensions with 4'-aminomethyl-4,5'8-trimethylpsoralen (AMT), the authors have investigated the residual levels and mutagenic potential of AMT after UVA phototreatment. The results suggest that residual available AMT is mutagenic in the AMES test and that the observed frameshift mutations may be caused by binding of AMt or its metabolites to nucleic acids in the absence of UVA light. (Author).

Mutagenic DNA repair in Escherichia coli. Pt. 2. Factors affecting loss of photoreversibility of UV induced mutations

Energy Technology Data Exchange (ETDEWEB)

Doubleday, O P; Bridges, B A; Green, M H.L. [Medical Research Council, Brighton (UK). Cell Mutation Unit

1975-01-01

The photoreversibility of UV-induced mutations to Trp/sup +/ 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.

Rice breeding with induced mutations in France

Energy Technology Data Exchange (ETDEWEB)

Marie, R [Station d' Amelioration des Plantes, Institut National de Recherches Agronomiques, Montpellier (France)

1970-03-01

Mutation experiments with rice at Montpellier yielded strains with improved lodging resistance, grain size, maturing time, milling quality and other characters. The general performance of these mutant strains was tested in field trials. Further mutagenic treatments were made to improve the high-yielding short grain varieties with regard to grain quality and seed dormancy. (author)

Separate and combined application of mutagens in bean (Phaseolus vulgaris L.)

International Nuclear Information System (INIS)

Milkov, E.

1989-01-01

The study included gamma rays (3, 6, 9, 12 kR) and EMS (0.05, 0.1, 0.15, 0.2% solutions), independently and in combination. Seeds of the cultivar ''Prelom'' were treated and the effects assessed in terms of plant survival. The doses of 6 kR gamma rays; 0.2% EMS and 6 kR + 0.2% EMS were found to be optimal (LD 50%). Mutations of interest for breeding were obtained. Although the survival rate after combined mutagen treatment was the same, the number of morphological variants in M 2 was much higher

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.

Effects of gamma radiations with or without chemical mutagens on rose seeds

International Nuclear Information System (INIS)

Lata, P.

1988-01-01

A preliminary experiment with seeds from 4 diploids, 17 tetraploids, 2 hexaploids and 1 octoploid roses confirmed that seed collection during early autumn under climatical conditions of London, gives a high percentage of viable seeds than those collected during late autumn. Seed stratification for about 100 days enhances germination when carried out under wet, purified sand. Harmful effects of radiations were recorded on seed germination, seedling survival, growth and flowering, after 0-120 Kr exposures of gamma rays. Rose cultivars were found to be more sensitive to radiations than the Rosa spp. The LD50 for diploid R. rugosa typica was between 20-30 Kr and for allo-tetraploid cultivar Aunty Dora, it was 8 Kr. No significant effect of radiations on seedling growth was recorded. Flowering in seedlings, raised from cultivar seeds, produced flowers during the first year of germination as compared with R. spp. seedlings which flowered after 3 to 4 years of germination. Among the chemical mutagens, Hydroxylamine produced least harmful effects on seed germination and survivals than those produced by Ethyl methane sulphonate; used alone or combined with low or high doses of radiations. The average seedling heights and number of leaves per seedlings were not affected. Mutagens were responsible for bringing about a loss in colour intensity which was more frequent when radiations and mutagens were used together. Real flower colour changes were rare and were attributed to the pollinating parent or mutagen or both. Present experiments indicate that although there are initial difficulties with seed germination but the resulting seedlings with increased genetic variability can generously reward a rose breeder in introducing new roses with rare combination of desirable characters which are difficult to accomplish merely by induced somatic mutations

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.

Lethal and mutagenic effects of ion beams and γ-rays in Aspergillus oryzae

International Nuclear Information System (INIS)

Toyoshima, Yoshiyuki; Takahashi, Akemi; Tanaka, Hisaki; Watanabe, Jun; Mogi, Yoshinobu; Yamazaki, Tatsuo; Hamada, Ryoko; Iwashita, Kazuhiro; Satoh, Katsuya; Narumi, Issay

2012-01-01

Highlights: ► We investigated the effects of different LET radiation in A. oryzae. ► Both γ-rays and ion beams induced base substitutions, frameshifts, deletions. ► Both γ-rays and ion beams induced genome-wide large-scale mutations in A. oryzae. ► Some differences in the types and frequencies of mutations were found. ► Our results provide new basic insights into the mutation breeding of A. oryzae. - Abstract: Aspergillus oryzae is a fungus that is used widely in traditional Japanese fermentation industries. In this study, the lethal and mutagenic effects of different linear energy transfer (LET) radiation in freeze-dried conidia of A. oryzae were investigated. The lethal effect, which was evaluated by a 90% lethal dose, was dependent on the LET value of the ionizing radiation. The most lethal ionizing radiation among that tested was 12 C 5+ ion beams with an LET of 121 keV/μm. The 12 C 5+ ion beams had a 3.6-times higher lethal effect than low-LET (0.2 keV/μm) γ-rays. The mutagenic effect was evaluated by the frequency of selenate resistant mutants. 12 C 6+ ion beams with an LET of 86 keV/μm were the most effective in inducing selenate resistance. The mutant frequency following exposure to 12 C 6+ ion beams increased with an increase in dose and reached 3.47 × 10 −3 at 700 Gy. In the dose range from 0 to 700 Gy, 12 C 5+ ion beams were the second most effective in inducing selenate resistance, the mutant frequency of which reached a maximum peak (1.67 × 10 −3 ) at 400 Gy. To elucidate the characteristics of mutation induced by ionizing radiation, mutations in the sulphate permease gene (sB) and ATP sulfurylase gene (sC) loci, the loss of function of which results in a selenate resistant phenotype, were compared between 12 C 5+ ion beams and γ-rays. We detected all types of transversions and transitions. For frameshifts, the frequency of a +1 frameshift was the highest in all cases. Although the incidence of deletions >2 bp was generally low

Mutation breeding newsletter. No. 46. Index issue no. 21-44

Energy Technology Data Exchange (ETDEWEB)

Maluszynski, M [ed.

2003-05-01

This is the third issue of Mutation Breeding Newsletter Index. To simplify the use of all three Indexes we retained, as much as possible, the previous structure and key words (mutant varieties, other mutants mentioned, varieties treated, other varieties mentioned, mutagens used, breeding objectives, and country). However, it should be considered that Latin names of species, their taxonomic relationships and common names have been left as published in Mutation Breeding Newsletters (MBNLs), following author's classification. Synonym species names, as well as names of the same variety but with different spelling or with typing error are presented in brackets. It should be noted that over this period of time the transcription rules from other alphabets to English have been changed a few times, especially in relation to Chinese and Russian languages, which leads to duplications or misunderstandings in preparation of successive issues of MBNL. The Index will also be available through our web site http://www.iaea.org/programmes/nafa/d2/index.html (click on Publications/Newsletters). We hope that now, in the era of the renaissance of applications of mutation techniques, this Index will become a very useful tool for plant breeders, geneticists and molecular biologists searching for information on mutated lines, mutagens and applied doses.

Mutation breeding newsletter. No. 46. Index issue no. 21-44

International Nuclear Information System (INIS)

Maluszynski, M.

2003-05-01

This is the third issue of Mutation Breeding Newsletter Index. To simplify the use of all three Indexes we retained, as much as possible, the previous structure and key words (mutant varieties, other mutants mentioned, varieties treated, other varieties mentioned, mutagens used, breeding objectives, and country). However, it should be considered that Latin names of species, their taxonomic relationships and common names have been left as published in Mutation Breeding Newsletters (MBNLs), following author's classification. Synonym species names, as well as names of the same variety but with different spelling or with typing error are presented in brackets. It should be noted that over this period of time the transcription rules from other alphabets to English have been changed a few times, especially in relation to Chinese and Russian languages, which leads to duplications or misunderstandings in preparation of successive issues of MBNL. The Index will also be available through our web site http://www.iaea.org/programmes/nafa/d2/index.html (click on Publications/Newsletters). We hope that now, in the era of the renaissance of applications of mutation techniques, this Index will become a very useful tool for plant breeders, geneticists and molecular biologists searching for information on mutated lines, mutagens and applied doses

Mutagenicity of the peroxisome proliferators clofibrate, Wyeth 14,643 and di-2-ethylhexyl phthalate in the lacZ plasmid-based transgenic mouse mutation assay

Directory of Open Access Journals (Sweden)

Boerrigter Michaël

2004-01-01

Full Text Available Abstract Background Peroxisome proliferators are considered rodent carcinogens that are putative human non-carcinogens based on the presumed absence of direct genetic toxicity in rodent and human cells and the resistance of human cells to the induction of peroxisomes by peroxisome proliferators. The highly sensitive lacZ plasmid-based transgenic mouse mutation assay was employed to investigate the mutagenicity of several peroxisome proliferators based on several lines of evidence suggesting that these agents may in fact exert a genotoxic effect. Methods Male and female lacZ-plasmid based transgenic mice were treated at 4 months of age with 6 doses of 2,333 mg di-2-ethylhexyl phthalate (DHEP, 200 mg Wyeth-14,643, or 90 mg clofibrate per kg of bodyweight, respectively, over a two-week period. Control animals were treated with the respective vehicles only (35% propyl glycol for DEHP and Wyeth-14,643 treatment controls and sterile water for clofibrate treatment controls. The mutant frequency in liver, kidney and spleen DNA was determined as the proportion of retrieved mutant and wild-type lacZ plasmids expressed in Escherichia Coli C host cells employing a positive selection system for mutant plasmids. Results Exposure to DEHP or Wyeth-14,643 significantly increased the mutant frequency in liver, but not in kidney or spleen, of both female and male mice. Treatment with clofibrate did not lead to an increased mutant frequency in any of the organs studied. Conclusion The results indicate that some peroxisome proliferators display an organ-specific mutagenicity in lacZ plasmid-based transgenic mice consistent with historical observations of organ- and compound-specific carcinogenicity.

Over-additive increase of bacterial mutations by combined action of ultraviolet light and alkylation

International Nuclear Information System (INIS)

Herrmann, S.; Hotz, G.; Herrlich, P.

1982-05-01

Mutagenic agents added in combination may contribute to an overall biological effect in proportion to the effect they would have if given individually. The combined effect may, however, not just be additive but rather result in a response above or below expectation if the two mutagenic pathways interacted at some level. We report here on one such example. Ultraviolet light and subsequent treatment with the alkylating agent ethylmethane-sulfonate (EMS) led to an over-additive increase of bacterial mutations. This is interesting with respect to unravelling the level mutagens interact. In addition such data may relate to the human situation which is only in the process of being assessed. (orig.) [de

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)

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.

Comparative effects in rats of intact wheat bran and two wheat bran fractions on the disposition of the mutagen 2-amino-3-methylimidazo[4,5-f]quinoline

International Nuclear Information System (INIS)

Ferguson, Lynnette R.; Harris, Philip J.; Kestell, Philip; Zhu, Shuotun; Munday, Rex; Munday, Christine M.

2011-01-01

Wheat bran protects against mutations and cancer, but contains different plant cell types that are likely to have different protective effects. We previously described the production and chemical characterisation of an aleurone-rich fraction (ARF) and a pericarp-rich fraction (PRF) from wheat grain. We compared these with whole bran (WB), fed to rats as 10% of a high fat AIN-76 diet. All bran-supplemented diets increased faecal bulk, in the order PRF > WB > ARF. PRF increased the activity of NAD(P)H:quinone acceptor oxidoreductase only in the forestomach, whereas ARF and WB enhanced levels of glutathione S-transferase in the duodenum. ARF but not PRF was digested and fermented, and also encouraged bacterial growth. Rats were gavaged with the radioactive mutagen 14 C-labelled IQ (2-amino-3-methylimidazo[4,5-f]quinoline), and effects of the brans on plasma radioactivity measured. Compared with the control diet, all bran-supplemented diets reduced the concentration of radioactivity in plasma, in the order ARF > PRF > WB. All brans increased faecal elimination of radioactivity, but only ARF and PRF enhanced urinary radioactivity. These data suggest that wheat bran may reduce mutation and cancers through direct adsorption and enhanced elimination of a dietary mutagen and/or its metabolites, and that wheat bran enriched in pericarp or aleurone cell walls may exert protective effects through different mechanisms.

Lethal and mutagenic effects of ion beams and γ-rays in Aspergillus oryzae.

Science.gov (United States)

Toyoshima, Yoshiyuki; Takahashi, Akemi; Tanaka, Hisaki; Watanabe, Jun; Mogi, Yoshinobu; Yamazaki, Tatsuo; Hamada, Ryoko; Iwashita, Kazuhiro; Satoh, Katsuya; Narumi, Issay

2012-12-01

Aspergillus oryzae is a fungus that is used widely in traditional Japanese fermentation industries. In this study, the lethal and mutagenic effects of different linear energy transfer (LET) radiation in freeze-dried conidia of A. oryzae were investigated. The lethal effect, which was evaluated by a 90% lethal dose, was dependent on the LET value of the ionizing radiation. The most lethal ionizing radiation among that tested was (12)C(5+) ion beams with an LET of 121keV/μm. The (12)C(5+) ion beams had a 3.6-times higher lethal effect than low-LET (0.2keV/μm) γ-rays. The mutagenic effect was evaluated by the frequency of selenate resistant mutants. (12)C(6+) ion beams with an LET of 86keV/μm were the most effective in inducing selenate resistance. The mutant frequency following exposure to (12)C(6+) ion beams increased with an increase in dose and reached 3.47×10(-3) at 700Gy. In the dose range from 0 to 700Gy, (12)C(5+) ion beams were the second most effective in inducing selenate resistance, the mutant frequency of which reached a maximum peak (1.67×10(-3)) at 400Gy. To elucidate the characteristics of mutation induced by ionizing radiation, mutations in the sulphate permease gene (sB) and ATP sulfurylase gene (sC) loci, the loss of function of which results in a selenate resistant phenotype, were compared between (12)C(5+) ion beams and γ-rays. We detected all types of transversions and transitions. For frameshifts, the frequency of a +1 frameshift was the highest in all cases. Although the incidence of deletions >2bp was generally low, deletions >20bp were characteristic for (12)C(5+) ion beams. γ-rays had a tendency to generate mutants carrying a multitude of mutations in the same locus. Both forms of radiation also induced genome-wide large-scale mutations including chromosome rearrangements and large deletions. These results provide new basic insights into the mutation breeding of A. oryzae using ionizing radiation. Crown Copyright © 2012. Published

Effective use of physical/chemical mutagens in crop hybrid breeding in China

Energy Technology Data Exchange (ETDEWEB)

Liu Luxiang; Wang Jing [Chinese Academy of Agricultural Sciences, Institute for Application of Atomic Energy, Beijing (China)

2001-03-01

Crop heterosis utilization was one of the greatest achievements in the agriculture production in the 20th century. It is proved that every breakthrough in crop hybrid breeding was predicated on the discovery or successful development of new heterosis germplasm. In recent years, in order to open up the scope and ways of using crop heterosis, it has been paid much close attention to apply mutation techniques to hybrid breeding. Useful tool materials like male sterile mutant lines, fertile restoration mutants in many crops have been obtained by effective use of physical/chemical mutagens. Brief introduction is made in this paper on the newest research improvement concerning the effective use of the techniques of mutation induction in China to create special useful genes, enrich the diversity of germplasm and promote the rapid development of crop hybrid breeding. (author)

Effective use of physical/chemical mutagens in crop hybrid breeding in China

International Nuclear Information System (INIS)

Liu Luxiang; Wang Jing

2001-01-01

Crop heterosis utilization was one of the greatest achievements in the agriculture production in the 20th century. It is proved that every breakthrough in crop hybrid breeding was predicated on the discovery or successful development of new heterosis germplasm. In recent years, in order to open up the scope and ways of using crop heterosis, it has been paid much close attention to apply mutation techniques to hybrid breeding. Useful tool materials like male sterile mutant lines, fertile restoration mutants in many crops have been obtained by effective use of physical/chemical mutagens. Brief introduction is made in this paper on the newest research improvement concerning the effective use of the techniques of mutation induction in China to create special useful genes, enrich the diversity of germplasm and promote the rapid development of crop hybrid breeding. (author)

Genome-scale mutational signatures of aflatoxin in cells, mice, and human tumors

Science.gov (United States)

Huang, Mi Ni; Yu, Willie; Teoh, Wei Wei; Ardin, Maude; Jusakul, Apinya; Ng, Alvin Wei Tian; Boot, Arnoud; Abedi-Ardekani, Behnoush; Villar, Stephanie; Myint, Swe Swe; Othman, Rashidah; Poon, Song Ling; Heguy, Adriana; Olivier, Magali; Hollstein, Monica; Tan, Patrick; Teh, Bin Tean; Sabapathy, Kanaga; Zavadil, Jiri; Rozen, Steven G.

2017-01-01

Aflatoxin B1 (AFB1) is a mutagen and IARC (International Agency for Research on Cancer) Group 1 carcinogen that causes hepatocellular carcinoma (HCC). Here, we present the first whole-genome data on the mutational signatures of AFB1 exposure from a total of >40,000 mutations in four experimental systems: two different human cell lines, in liver tumors in wild-type mice, and in mice that carried a hepatitis B surface antigen transgene—this to model the multiplicative effects of aflatoxin exposure and hepatitis B in causing HCC. AFB1 mutational signatures from all four experimental systems were remarkably similar. We integrated the experimental mutational signatures with data from newly sequenced HCCs from Qidong County, China, a region of well-studied aflatoxin exposure. This indicated that COSMIC mutational signature 24, previously hypothesized to stem from aflatoxin exposure, indeed likely represents AFB1 exposure, possibly combined with other exposures. Among published somatic mutation data, we found evidence of AFB1 exposure in 0.7% of HCCs treated in North America, 1% of HCCs from Japan, but 16% of HCCs from Hong Kong. Thus, aflatoxin exposure apparently remains a substantial public health issue in some areas. This aspect of our study exemplifies the promise of future widespread resequencing of tumor genomes in providing new insights into the contribution of mutagenic exposures to cancer incidence. PMID:28739859

Preliminary study on mutagenic effects of heavy ions irradiation on maize inbred lines

International Nuclear Information System (INIS)

Yu Lixia; Li Wenjian; Xie Hongmei; Chen Xuejun; Chen Jing

2010-01-01

In order to study mutagenic effects of different heavy ions irradiation on maize inbred lines,corn seeds of Zheng58, Lu9801, Jinxiang4C-1, CSR24001, 308 and 478 were irradiated with 12 C 6+ and 36 Ar 18+ ions. The experimental results showed that the germination rate and planting percent were different after irradiation. The wettish seeds had higher sensibility to heavy ion irradiation. The leaf type of the plant appeared visible changes in M 1 generation. In M 2 generation, great changes had taken place in economic traits, many of which are beneficial mutation. Some beneficia1 mutation could be stably inherited in M 3 generation. From the above, it can be predicted that heavy ions irradiation is an effective means of genetic improvement of maize. (authors)

Lethal and mutagenic effects of fast neutrons of different energy on Streptomyces griseus spores

International Nuclear Information System (INIS)

Podgorskaya, M.E.; Tulina, G.G.; Serdechnaya, A.I.; Matselyukh, B.P.

1986-01-01

A study was made of lethal and mutagenic effects of fast neutrons of different energy on spores of prototrophic and auxotrophic strains of Streptomyces griseus. Relative biological effectiveness of fast neutrons is higher than that of γ-rays and depends on beam energy. Neutrons of 22-50 MeV induce Streptomyces griseus mutations more frequently (by one order of magnitude) than neutrons of 1.4-1.6 MeV do. The obtained mutants can be used in studying Streptomyces griseus genetics

Induced skeletal mutations

International Nuclear Information System (INIS)

Selby, P.B.

1979-01-01

This paper describes a large-scale experiment that, by means of breeding tests, confirmed that many dominant skeletal mutations are induced by large-dose radiation exposure. The author also discusses: (1) the major advantages and disadvantages of the skeletal method in improving estimates of genetic hazard to man; (2) future uses of the skeletal method; (3) direct estimation of risk beyond the first generation using the skeletal method; and (4) the possibility of using the skeletal method as a quick and easy screen for chemical mutagens

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.

Enhanced sensitivity to mutagens - EMS, MH, SM by pre-soaking - A taxometric study based on M{sub 1} parameters in finger millet

Energy Technology Data Exchange (ETDEWEB)

Singh, B; Sinha, S.K. [Plant Breeding and Genetics, OUAT, Bhubaneswar (India)], E-mail: sing_baburam@yahoo.co.in

2008-07-01

Pre-soaking seeds before treatment enhances sensitivity to many chemical mutagens; but little work has been done with maleic hydrazide (MH), a chromosome breaking agent and preferential inducer of micromutation and streptomycin (SM), a cytoplasmic mutagen. In the present investigation on pre-soaking (PS) effects in finger millet (Eleusine coracana, Gaertn), we included these two mutagens, besides one commonly used mutagen, EMS to determine a common effective PS range usingM{sub 1}seedling traits. Since differentM{sub 1}parameters, mutagens and their doses showed different peaks of response, we adopted a taxometric approach using all characters together. Combinations of chemicals, doses and sixM{sub 1}seedling attributes gave 48 characters for the numerical classification of PS periods (0, 8, 10, 12, 14, 16 and 18 h) as OTUs. Dendrogram from the similarity matrix using UPGMA clustering showed two clusters : (1) Cl. 1 of three OTUs (0, 8 and 10 h PS) and (2) Cl.2 of four OTUs(12-18h PS).We considered 12-18h as effective PS range and 0-10h as ineffective for all kinds of mutagens. The effective range would contain the major peak of sensitivity; the ineffective range might show a small peak. We confirmed these inferences with SM induced albinism as an indicator of plastid mutations. Higher doses shifted the peak within the effective range towards lower PS and low dose towards longer PS. Taxometrics could be usefully adopted in mutagenesis studies. (author)

Investigating the effects of dietary folic acid on sperm count, DNA damage and mutation in Balb/c mice

International Nuclear Information System (INIS)

Swayne, Breanne G.; Kawata, Alice; Behan, Nathalie A.; Williams, Andrew; Wade, Mike G.; MacFarlane, Amanda J.; Yauk, Carole L.

2012-01-01

To date, fewer than 50 mutagens have been studied for their ability to cause heritable mutations. The majority of those studied are classical mutagens like radiation and anti-cancer drugs. Very little is known about the dietary variables influencing germline mutation rates. Folate is essential for DNA synthesis and methylation and can impact chromatin structure. We therefore determined the effects of folic acid-deficient (0 mg/kg), control (2 mg/kg) and supplemented (6 mg/kg) diets in early development and during lactation or post-weaning on mutation rates and chromatin quality in sperm of adult male Balb/c mice. The sperm chromatin structure assay and mutation frequencies at expanded simple tandem repeats (ESTRs) were used to evaluate germline DNA integrity. Treatment of a subset of mice fed the control diet with the mutagen ethylnitrosourea (ENU) at 8 weeks of age was included as a positive control. ENU treated mice exhibited decreased cauda sperm counts, increased DNA fragmentation and increased ESTR mutation frequencies relative to non-ENU treated mice fed the control diet. Male mice weaned to the folic acid deficient diet had decreased cauda sperm numbers, increased DNA fragmentation index, and increased ESTR mutation frequency. Folic acid deficiency in early development did not lead to changes in sperm counts or chromatin integrity in adult mice. Folic acid supplementation in early development or post-weaning did not affect germ cell measures. Therefore, adequate folic acid intake in adulthood is important for preventing chromatin damage and mutation in the male germline. Folic acid supplementation at the level achieved in this study does not improve nor is it detrimental to male germline chromatin integrity.

Investigating the effects of dietary folic acid on sperm count, DNA damage and mutation in Balb/c mice

Energy Technology Data Exchange (ETDEWEB)

Swayne, Breanne G.; Kawata, Alice [Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, K1A 0K9 (Canada); Behan, Nathalie A. [Nutrition Research Division, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, K1A 0K9 (Canada); Williams, Andrew; Wade, Mike G. [Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, K1A 0K9 (Canada); MacFarlane, Amanda J. [Nutrition Research Division, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, K1A 0K9 (Canada); Yauk, Carole L., E-mail: carole.yauk@hc-sc.ga.ca [Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, K1A 0K9 (Canada)

2012-09-01

To date, fewer than 50 mutagens have been studied for their ability to cause heritable mutations. The majority of those studied are classical mutagens like radiation and anti-cancer drugs. Very little is known about the dietary variables influencing germline mutation rates. Folate is essential for DNA synthesis and methylation and can impact chromatin structure. We therefore determined the effects of folic acid-deficient (0 mg/kg), control (2 mg/kg) and supplemented (6 mg/kg) diets in early development and during lactation or post-weaning on mutation rates and chromatin quality in sperm of adult male Balb/c mice. The sperm chromatin structure assay and mutation frequencies at expanded simple tandem repeats (ESTRs) were used to evaluate germline DNA integrity. Treatment of a subset of mice fed the control diet with the mutagen ethylnitrosourea (ENU) at 8 weeks of age was included as a positive control. ENU treated mice exhibited decreased cauda sperm counts, increased DNA fragmentation and increased ESTR mutation frequencies relative to non-ENU treated mice fed the control diet. Male mice weaned to the folic acid deficient diet had decreased cauda sperm numbers, increased DNA fragmentation index, and increased ESTR mutation frequency. Folic acid deficiency in early development did not lead to changes in sperm counts or chromatin integrity in adult mice. Folic acid supplementation in early development or post-weaning did not affect germ cell measures. Therefore, adequate folic acid intake in adulthood is important for preventing chromatin damage and mutation in the male germline. Folic acid supplementation at the level achieved in this study does not improve nor is it detrimental to male germline chromatin integrity.

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

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.

UVA activation of N-dialkylnitrosamines releasing nitric oxide, producing strand breaks as well as oxidative damages in DNA, and inducing mutations in the Ames test

International Nuclear Information System (INIS)

Arimoto-Kobayashi, Sakae; Sano, Kayoko; Machida, Masaki; Kaji, Keiko; Yakushi, Keiko

2010-01-01

We investigated the photo-mutagenicity and photo-genotoxicity of N-dialkylnitrosamines and its mechanisms of UVA activation. With simultaneous irradiation of UVA, photo-mutagenicity of seven N-dialkylnitrosamines was observed in Ames bacteria (Salmonella typhimurium TA1535) in the absence of metabolic activation. Mutagenicity of pre-irradiated N-dialkylnitrosamines was also observed with S. typhimurium hisG46, TA100, TA102 and YG7108 in the absence of metabolic activation. UVA-mediated mutation with N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) decreased by adding either the NO or OH radical scavenger. When superhelical DNA was irradiated with N-dialkylnitrosamines, nicked circular DNA appeared. Ten N-dialkylnitrosamines examined produced strand breaks in the treated DNA in the presence of UVA. The level of single-strand breaks in φX174 DNA mediated by N-nitrosomorpholine (NMOR) and UVA decreased by adding either a radical scavenger or superoxide dismutase. When calf thymus DNA was treated with N-dialkylnitrosamines (NDMA, NDEA, NMOR, N-nitrosopyrrolidine (NPYR) and N-nitrosopiperidine (NPIP)) and UVA, the ratio of 8-oxodG/dG in the DNA increased. Action spectra were obtained to determine if nitrosamine acts as a sensitizer of UVA. Both mutation frequency and NO formation were highest at the absorption maximum of nitrosamines, approximately 340 nm. The plots of NO formation and mutation frequency align with the absorption curve of NPYR, NMOR and NDMA. A significant linear correlation between the optical density of N-dialkynitrosamines at 340 nm and NO formation in each irradiated solution was revealed by ANOVA. We would like to propose the hypothesis that the N-nitroso moiety of N-dialkylnitrosamines absorbs UVA photons, UVA-photolysis of N-dialkylnitrosamines brings release of nitric oxide, and subsequent production of alkyl radical cations and active oxygen species follow as secondary events, which cause DNA strand breaks, oxidative and

UVA activation of N-dialkylnitrosamines releasing nitric oxide, producing strand breaks as well as oxidative damages in DNA, and inducing mutations in the Ames test

Energy Technology Data Exchange (ETDEWEB)

Arimoto-Kobayashi, Sakae [Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima, Okayama 700-8530 (Japan); Sano, Kayoko; Machida, Masaki; Kaji, Keiko; Yakushi, Keiko [Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima, Okayama 700-8530 (Japan)

2010-09-10

We investigated the photo-mutagenicity and photo-genotoxicity of N-dialkylnitrosamines and its mechanisms of UVA activation. With simultaneous irradiation of UVA, photo-mutagenicity of seven N-dialkylnitrosamines was observed in Ames bacteria (Salmonella typhimurium TA1535) in the absence of metabolic activation. Mutagenicity of pre-irradiated N-dialkylnitrosamines was also observed with S. typhimurium hisG46, TA100, TA102 and YG7108 in the absence of metabolic activation. UVA-mediated mutation with N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) decreased by adding either the NO or OH radical scavenger. When superhelical DNA was irradiated with N-dialkylnitrosamines, nicked circular DNA appeared. Ten N-dialkylnitrosamines examined produced strand breaks in the treated DNA in the presence of UVA. The level of single-strand breaks in {phi}X174 DNA mediated by N-nitrosomorpholine (NMOR) and UVA decreased by adding either a radical scavenger or superoxide dismutase. When calf thymus DNA was treated with N-dialkylnitrosamines (NDMA, NDEA, NMOR, N-nitrosopyrrolidine (NPYR) and N-nitrosopiperidine (NPIP)) and UVA, the ratio of 8-oxodG/dG in the DNA increased. Action spectra were obtained to determine if nitrosamine acts as a sensitizer of UVA. Both mutation frequency and NO formation were highest at the absorption maximum of nitrosamines, approximately 340 nm. The plots of NO formation and mutation frequency align with the absorption curve of NPYR, NMOR and NDMA. A significant linear correlation between the optical density of N-dialkynitrosamines at 340 nm and NO formation in each irradiated solution was revealed by ANOVA. We would like to propose the hypothesis that the N-nitroso moiety of N-dialkylnitrosamines absorbs UVA photons, UVA-photolysis of N-dialkylnitrosamines brings release of nitric oxide, and subsequent production of alkyl radical cations and active oxygen species follow as secondary events, which cause DNA strand breaks, oxidative and

On the mutagenicity of methadone hydrochloride. Induced dominant lethal mutation and spermatocyte chromosomal aberrations in treated males.

Science.gov (United States)

Badr, F M; Rabouh, S A; Badr, R S

1979-11-01

The mutagenicity of methadone hydrochloride was tested in male mice using the dominant lethal mutation technique and the spermatocyte test of treated mice. Male mice of C3H inbred strain received one of the following doses, 1, 2, 4 or 6 mg/kg body weight once a day for 3 consecutive days. Another group of mice served as control and received saline instead. Treated males were then mated to virgin females at 3-day intervals for a period of 45 days. Pregnant females were dissected at mid-term and the corpora lutea and intrauterine contents were recorded. The spermatocytes of treated males were examined 45-50 d after treatments with methadone and abnormal pairing configurations were scored. The methadone treatment was found to increase the rate of preimplantation deaths consistently in all post-meiotic stages with all doses used. In addition, the higher doses, 4 and 6 mg, affected spermatogonia stages. Quantitatively, the dose-response relationship cannot be demonstrated though the spectrum of effect increased with higher doses as more spermatogenesis stages became more sensitive to the treatment. In many cases the frequency of live implants showed a positive correlation with preimplantation deaths in contrast with the frequency of early deaths which showed only sporadic variation. The mutation indices based on total embryonic death indicate that methadone hydrochloride affected several stages of germ-cell maturation namely, spermatozoa (M.I. 14-35), late spermatids (M.I. 15-48), early spermatids (M.I. 14-50), late spermatocytes (M.I. 15-43) and spermatogonial stages (M.I. 12-63). Chromosome analysis at diakinesis-metaphase 1 revealed significant increase in the frequency of sex chromosome and autosome univalents with different doses of methadone. The smallest dose applied was quite effective and the data represent direct dose-response relationship. Of the multivalent configuration, the most frequent type was chain quadrivalents. The frequencies of total translocations

Induction of rice mutations by high hydrostatic pressure.

Science.gov (United States)

Zhang, Wei; Liu, Xuncheng; Zheng, Feng; Zeng, Songjun; Wu, Kunlin; da Silva, Jaime A Teixeira; Duan, Jun

2013-09-01

High hydrostatic pressure (HHP) is an extreme thermo-physical factor that affects the synthesis of DNA, RNA and proteins and induces mutagenesis in microorganisms. Our previous studies showed that exposure to 25-100 MPa HHP for 12 h retarded the germination and affected the viability of rice (Oryza sativa L.) seeds, increased the tolerance of rice plants to cold stress and altered gene expression patterns in germinating rice seeds. However, the mutagenic effect of HHP on rice remains unknown. In this study, exposure to 25, 50, 75 or 100 MPa for 12 h HHP could efficiently induce variation in rice plants. Furthermore, presoaking time and HHP strength during HHP treatment affected the efficiency of mutation. In addition, the Comet assay revealed that exposure to 25-100 MPa HHP for 12 h induced DNA strand breakage in germinating seeds and may have been the source of mutations. Our results suggest that HHP is a promising physical mutagen in rice breeding. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Study on the mutagenic effects of a new chelating agent (7603) used for accelerating excretion of radionuclides

International Nuclear Information System (INIS)

Shen Binyuan; Luo Meichu; Zhen Guibao; Ruan Tianming; Feng Jialin; Cao Qunli

1989-01-01

The results of studies on the mutagenic effects of a new chelating agent, Suo An Quan (7603) or 5-methxlene Iminodiaeticaid Vanillin, was reported in this paper. For this agent, no mutagenesis was found by the reverse mutation test of Salmonella typhi munine (Amos test), the test of chromosome aberrations in Chinese hamster oocytes (CHO cells), and the test of micronucleus in polychromatic erythrocytes of the bone marrow in mice

40 CFR 798.5265 - The salmonella typhimurium reverse mutation assay.

Science.gov (United States)

2010-07-01

... mean number of revertant colonies per plate and standard deviation shall be presented for test chemical... revertant colonies per plate, standard deviation. (vi) Dose-response relationship, if applicable. (g... Salmonella/ mammalian-microsome mutagenicity test,” Mutation Research 31:347-364 (1975). (2) de Serres, F.J...

Bacterial and human cell mutagenicity study of some C[sub 18]H[sub 10] cyclopenta-fused polycyclic aromatic hydrocarbons associated with fossil fuels combustion

Energy Technology Data Exchange (ETDEWEB)

Lafleur, A.L.; Longwell, J.P.; Marr, J.A.; Monchamp, P.A.; Thilly, W.G. (Massachusetts Institute of Technology, Cambridge (United States)); Mulder, P.P.Y.; Boere, B.B.; Cornelisse, J.; Lugtenburg, J. (Univ. of Leiden (Netherlands))

1993-06-01

A number of isomeric C[sub 18]H[sub 10] polycyclic aromatic hydrocarbons (PAHs), thought to be primarily cyclopenta-fused PAHs, are produced during the combustion and pyrolysis of fossil fuels. To determine the importance of their contributions to the total mutagenic activity of combustion and pyrolysis samples in which they are found, we characterized reference quantities of four C[sub 18]H[sub 10] CP-PAHs: benzol [ghi] fluoranthene (BF), cyclopenta [cd] pyrene (CPP), cyclopent [hi] acephenanthrylene (CPAP), and cyclopent [hi] acaenthrylene (CPAA). Synthesis of CPAA and CPAP is described. The availability of reference samples of these isomers also proved to be an essential aid in the identification of the C[sub 18]H[sub 10] species often found in combustion and pyrolysis samples. Chemical analysis of selected combustion and pyrolysis samples showed that CPP was generally the most abundant C[sub 18]H[sub 10] isomer, followed by CPAP and BF. CPAA was detected only in pyrolysis products from pure PAHs. We tested the four C[sub 18]H[sub 10] PAHs for mutagenicity in a forward mutation assay using S. typhimurium. CPP, BF, and CPAA were roughly twice as mutagenic as benzo[a]pyrene (BaP), whereas CPAP was only slightly active. These PAHs were also tested for mutagenic activity in human cells. In this assay, CPP and CPAA were strongly mutagenic but less active than BaP, whereas CPAP and BF were inactive at the dose levels tested. Also, the bacterial and human cell mutagenicity of CPAA and CPAP were compared with the mutagenicity of their monocyclopenta-fused analogs, aceanthrylene and acephenanthrylene. Although the mutagenicities of CPAP and acephenanthrylene are similar, the mutagenic activity of CPAA is an order of magnitude greater than that of aceanthrylene.

Mutational synergism between p-fluorophenylalaline and UV in Coprinus lagopus

International Nuclear Information System (INIS)

Talmud, P.J.

1977-01-01

The amino acid analogue p-fluorophenylalanine (PFP) is mutagenic to Coprinus lagopus due to its incorporation into proteins. Spontaneous mutations, PFP and UV mutagenesis and PFP/UV synergism have been studied in a UV resistant strain and in two complementing UV sensitive mutant strains. By comparison to the UV resistant strain, one UV sensitive strain shows normal spontaneous mutations, 1.4% PFP-induced mutations and 50-fold UV mutagenesis. The second UV sensitive strain has 19-fold spontaneous mutation frequency and slightly elevated UV mutagenesis. In all 3 strains the PFP/UV synergism is comparable (4-5 times the arithmetic expected). The results indicate that PFP mutagenesis is due to the incorporation of PFP into enzymes normally functioning in the organism but which also participate in UV repair mechanisms. A model is proposed for UV repair which is based on a PFP sensitive excision repair system of at least two enzymes, an alternative 'error-proof' pathway which is not susceptible to PFP and an 'error-prone' pathway which is responsible for UV mutagenesis and is susceptible to PFP as shown by the PFP/UV synergism. Because PFP is given before UV treatment, this implies a UV inducible cofactor and a PFP sensitive enzyme which only functions after UV activation

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

In vivo somatic mutation systems in the mouse

International Nuclear Information System (INIS)

Russell, L.B.

1979-01-01

In an effort to meet the need for a fast and cheap in vivo prescreen for inherited mammalian point mutations, a somatic forward-mutation method, originally developed in an x-ray experiment, has more recently been tested in work with chemical mutagens. The method makes use of coat-color mutations because the gene product is usually locally expressed, mosaics can be detected with minimal effort, and opportunities for making comparison with induction of germinal point mutations are greatest.--Following treatment of embryos that are heterozygous at specific coat-color loci, various induced genetic changes can result in expression of the recessive (RS) in clones derived from mutant melanocyte precursor cells. However, other events, such as decrease in the number of precursor cells, or disturbed differentiation, can also result in spots, which with careful classification can usually be distinguished from RS's on the basis of their location and color. When this is done, the relative RS frequencies for a series of compounds at least roughly parallel the relative spermatogonial mutation rates. The fact that easily measurable (though low) RS rates are obtained with compounds that have yielded negative results in spermatogonial tests is not surprising in view of the fact that RS's can be caused by several mechanisms besides point mutation.--In spite of the parallelism observed in one laboratory, the usefulness of the in vivo somatic mutation method as a prescreen could come to be doubted because of major discrepancies between results of similar experiments at different laboratories. However, It appears probable that at least some of these discrepancies are due to failure to discriminate between spots that probably resulted from melanocyte insufficiency and spots that resulted from expression of the recessive.--Reverse somatic mutation systems can potentially avoid some of the pitfalls of forward mutation systems. Such system are still in developmental stages

The dual nature of mismatch repair as antimutator and mutator: for better or for worse

Directory of Open Access Journals (Sweden)

Sara Thornby Bak

2014-08-01

Full Text Available DNA is constantly under attack by a number of both exogenous and endogenous agents that challenge its integrity. Among the mechanisms that have evolved to counteract this deleterious action, mismatch repair (MMR has specialized in removing DNA biosynthetic errors that occur when replicating the genome. Malfunction or inactivation of this system results in an increase in spontaneous mutability and a strong predisposition to tumor development. Besides this key corrective role, MMR proteins are involved in other pathways of DNA metabolism such as mitotic and meiotic recombination and processing of oxidative damage. Surprisingly, MMR is also required for certain mutagenic processes. The mutagenic MMR has beneficial consequences contributing to the generation of a vast repertoire of antibodies through class switch recombination and somatic hypermutation processes. However, this non-canonical mutagenic MMR also has detrimental effects; it promotes repeat expansions associated with neuromuscular and neurodegenerative diseases and may contribute to cancer/disease-related aberrant mutations and translocations. The reaction responsible for replication error correction has been the most thoroughly studied and it is the subject to numerous reviews. This review describes briefly the biochemistry of MMR and focuses primarily on the non-canonical MMR activities described in mammals as well as emerging research implicating interplay of MMR and chromatin.

Effects of a mutation on the folding mechanism of a β-hairpin

NARCIS (Netherlands)

Juraszek, J.; Bolhuis, P.G.

2009-01-01

The folding mechanism of a protein is determined by its primary sequence. Yet, how the mechanism is changed by a mutation is still poorly understood, even for basic secondary structures such as β-hairpins. We perform an extensive simulation study of the effects of mutating the GB1 β-hairpin into

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.

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

Induction of two mutants in birdsfoot trefoil (Lotus corniculatus) by x-rays and chemical mutagens

International Nuclear Information System (INIS)

Therrien, M.C.; Grant, W.F.

1982-01-01

The mutagenic effects of X-rays, ethyl methanesulfonate (EMS), 8-ethoxycaffeine (EOC), N-hydroxyurea (HU) and 2-aminopurine (2AP) on seed treatment of birdsfoot trefoil (Lotus corniculatus L. 'Mirabel') were assessed over four generations. Mutants were recovered in the M 2 , M 3 and M 4 generations from selfed lines, from crosses derived form selfed lines and from open pollination lines. Mutant plants exhibiting vestigial floret character were recovered from X-rays, EMS, EOC and HU treatments. Mutant chlorotica plants were obtained from EMS treatment only. No mutants were recovered from 2AP treatment, EMS, the most effective mutagen, produced nine vestigial floret and 12 chlorotica mutants. Mutants were obtained from only one exposure of X-rays (12 krad). There was evidence for preferential elimination of gametes. The chlorotica and vestigial floret mutants were inherited as tetrasomic recessives. Mutation frequencies of 0.4 - 3.1% in a tetrasomic background are indicative of the effectiveness of EMS in birdsfoot trefoil

Induction of two mutants in birdsfoot trefoil (Lotus corniculatus) by x-rays and chemical mutagens

Energy Technology Data Exchange (ETDEWEB)

Therrien, M.C.; Grant, W.F. (McGill Univ., Ste. Anne de Bellevue, Quebec (Canada). Macdonald Coll.)

1982-10-01

The mutagenic effects of X-rays, ethyl methanesulfonate (EMS), 8-ethoxycaffeine (EOC), N-hydroxyurea (HU) and 2-aminopurine (2AP) on seed treatment of birdsfoot trefoil (Lotus corniculatus L. 'Mirabel') were assessed over four generations. Mutants were recovered in the M/sub 2/, M/sub 3/ and M/sub 4/ generations from selfed lines, from crosses derived form selfed lines and from open pollination lines. Mutant plants exhibiting vestigial floret character were recovered from X-rays, EMS, EOC and HU treatments. Mutant chlorotica plants were obtained from EMS treatment only. No mutants were recovered from 2AP treatment, EMS, the most effective mutagen, produced nine vestigial floret and 12 chlorotica mutants. Mutants were obtained from only one exposure of X-rays (12 krad). There was evidence for preferential elimination of gametes. The chlorotica and vestigial floret mutants were inherited as tetrasomic recessives. Mutation frequencies of 0.4 - 3.1% in a tetrasomic background are indicative of the effectiveness of EMS in birdsfoot trefoil.

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

Quantitative Analysis of the Mutagenic Potential of 1-Aminopyrene-DNA Adduct Bypass Catalyzed by Y-Family DNA Polymerases

Science.gov (United States)

Sherrer, Shanen M.; Taggart, David J.; Pack, Lindsey R.; Malik, Chanchal K.; Basu, Ashis K.; Suo, Zucai

2012-01-01

N- (deoxyguanosin-8-yl)-1-aminopyrene (dGAP) is the predominant nitro polyaromatic hydrocarbon product generated from the air pollutant 1-nitropyrene reacting with DNA. Previous studies have shown that dGAP induces genetic mutations in bacterial and mammalian cells. One potential source of these mutations is the error-prone bypass of dGAP lesions catalyzed by the low-fidelity Y-family DNA polymerases. To provide a comparative analysis of the mutagenic potential of the translesion DNA synthesis (TLS) of dGAP, we employed short oligonucleotide sequencing assays (SOSAs) with the model Y-family DNA polymerase from Sulfolobus solfataricus, DNA Polymerase IV (Dpo4), and the human Y-family DNA polymerases eta (hPolη), kappa (hPolκ), and iota (hPolι). Relative to undamaged DNA, all four enzymes generated far more mutations (base deletions, insertions, and substitutions) with a DNA template containing a site-specifically placed dGAP. Opposite dGAP and at an immediate downstream template position, the most frequent mutations made by the three human enzymes were base deletions and the most frequent base substitutions were dAs for all enzymes. Based on the SOSA data, Dpo4 was the least error-prone Y-family DNA polymerase among the four enzymes during the TLS of dGAP. Among the three human Y-family enzymes, hPolκ made the fewest mutations at all template positions except opposite the lesion site. hPolκ was significantly less error-prone than hPolι and hPolη during the extension of dGAP bypass products. Interestingly, the most frequent mutations created by hPolι at all template positions were base deletions. Although hRev1, the fourth human Y-family enzyme, could not extend dGAP bypass products in our standing start assays, it preferentially incorporated dCTP opposite the bulky lesion. Collectively, these mutagenic profiles suggest that hPolkk and hRev1 are the most suitable human Y-family DNA polymerases to perform TLS of dGAP in humans. PMID:22917544

Association between mutation spectra and stable and unstable DNA adduct profiles in Salmonella for benzo[a]pyrene and dibenzo[a,l]pyrene

Energy Technology Data Exchange (ETDEWEB)

DeMarini, David M., E-mail: demarini.david@epa.gov [Integrated Systems Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Hanley, Nancy M.; Warren, Sarah H.; Adams, Linda D.; King, Leon C. [Integrated Systems Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

2011-09-01

Highlights: {yields} Benzo[a]pyrene (BP) induces stable DNA adducts and mutations primarily at guanine. {yields} Dibenzo[a,l]pyrene (DBP) induces them primarily at adenine. {yields} BP induces abasic sites, but DBP does not in the Salmonella mutagenicity assay. {yields} Stable DNA adducts alone appear to account for the mutation spectrum of DBP. {yields} Stable DNA adducts and possibly abasic sites account for the mutation spectrum of BP. - Abstract: Benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) are two polycyclic aromatic hydrocarbons (PAHs) that exhibit distinctly different mutagenicity and carcinogenicity profiles. Although some studies show that these PAHs produce unstable DNA adducts, conflicting data and arguments have been presented regarding the relative roles of these unstable adducts versus stable adducts, as well as oxidative damage, in the mutagenesis and tumor-mutation spectra of these PAHs. However, no study has determined the mutation spectra along with the stable and unstable DNA adducts in the same system with both PAHs. Thus, we determined the mutagenic potencies and mutation spectra of BP and DBP in strains TA98, TA100 and TA104 of Salmonella, and we also measured the levels of abasic sites (aldehydic-site assay) and characterized the stable DNA adducts ({sup 32}P-postlabeling/HPLC) induced by these PAHs in TA104. Our results for the mutation spectra and site specificity of stable adducts were consistent with those from other systems, showing that DBP was more mutagenic than BP in TA98 and TA100. The mutation spectra of DBP and BP were significantly different in TA98 and TA104, with 24% of the mutations induced by BP in TA98 being complex frameshifts, whereas DBP produced hardly any of these mutations. In TA104, BP produced primarily GC to TA transversions, whereas DBP produced primarily AT to TA transversions. The majority (96%) of stable adducts induced by BP were at guanine, whereas the majority (80%) induced by DBP were at adenine

Lethal and mutagenic effects of ion beams and γ-rays in Aspergillus oryzae

Energy Technology Data Exchange (ETDEWEB)

Toyoshima, Yoshiyuki, E-mail: toyoshima@yamasa.com [Soy Sauce Laboratory, Yamasa Corporation, 2-10-1 Araoicho, Choshi, Chiba 288-0056 (Japan); Takahashi, Akemi; Tanaka, Hisaki; Watanabe, Jun; Mogi, Yoshinobu; Yamazaki, Tatsuo [Soy Sauce Laboratory, Yamasa Corporation, 2-10-1 Araoicho, Choshi, Chiba 288-0056 (Japan); Hamada, Ryoko; Iwashita, Kazuhiro [Fundamental Research Division, National Research Institute of Brewing, 3-7-1 Kagamiyama, Higashihiroshima, Hiroshima 739-0046 (Japan); Satoh, Katsuya; Narumi, Issay [Ion Beam Mutagenesis Research Group, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan)

2012-12-15

Highlights: ► We investigated the effects of different LET radiation in A. oryzae. ► Both γ-rays and ion beams induced base substitutions, frameshifts, deletions. ► Both γ-rays and ion beams induced genome-wide large-scale mutations in A. oryzae. ► Some differences in the types and frequencies of mutations were found. ► Our results provide new basic insights into the mutation breeding of A. oryzae. - Abstract: Aspergillus oryzae is a fungus that is used widely in traditional Japanese fermentation industries. In this study, the lethal and mutagenic effects of different linear energy transfer (LET) radiation in freeze-dried conidia of A. oryzae were investigated. The lethal effect, which was evaluated by a 90% lethal dose, was dependent on the LET value of the ionizing radiation. The most lethal ionizing radiation among that tested was {sup 12}C{sup 5+} ion beams with an LET of 121 keV/μm. The {sup 12}C{sup 5+} ion beams had a 3.6-times higher lethal effect than low-LET (0.2 keV/μm) γ-rays. The mutagenic effect was evaluated by the frequency of selenate resistant mutants. {sup 12}C{sup 6+} ion beams with an LET of 86 keV/μm were the most effective in inducing selenate resistance. The mutant frequency following exposure to {sup 12}C{sup 6+} ion beams increased with an increase in dose and reached 3.47 × 10{sup −3} at 700 Gy. In the dose range from 0 to 700 Gy, {sup 12}C{sup 5+} ion beams were the second most effective in inducing selenate resistance, the mutant frequency of which reached a maximum peak (1.67 × 10{sup −3}) at 400 Gy. To elucidate the characteristics of mutation induced by ionizing radiation, mutations in the sulphate permease gene (sB) and ATP sulfurylase gene (sC) loci, the loss of function of which results in a selenate resistant phenotype, were compared between {sup 12}C{sup 5+} ion beams and γ-rays. We detected all types of transversions and transitions. For frameshifts, the frequency of a +1 frameshift was the highest in all

Anti-mutagenic and Pro-apoptotic Effects of Apigenin on Human Chronic Lymphocytic Leukemia Cells

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Mehrdad Hashemi

2010-09-01

Full Text Available "nDiet can play a vital role in cancer prevention. Nowadays the scientists are looking for food materials which can potentially prevent the cancer occurrence. The purpose of this research is to examine anti-mutagenic and apoptotic effects of apigenin in human lymphoma cells. In present study human chronic lymphocytic leukemia (Eheb cell line were cultured in RPMI 1640 (Sigma, supplemented with 10% fetal calf serum, penicillin-streptomycin, L-glutamine and incubated at 37 ºC for 2 days. In addition cancer cell line was treated by and apigenin and cellular vital capacity was determined by MTT assay. Then effect of apigenin in human lymphoma B cells was examined by flow cytometry techniques. The apigenin was subsequently evaluated in terms of anti-mutagenic properties by a standard reverse mutation assay (Ames test. This was performed with histidine auxotroph strain of Salmonella typhimurium (TA100. Thus, it requires histidine from a foreign supply to ensure its growth. The aforementioned strain gives rise to reverted colonies when expose to sodium azide as a carcinogen substance. During MTT assay, human chronic lymphocytic leukemia revealed to have a meaningful cell death when compared with controls (P<0.01 Apoptosis was induced suitably after 48 hours by flow cytometry assay. In Ames test apigenin prevented the reverted mutations and the hindrance percent of apigenin was 98.17%.These results have revealed apigenin induced apoptosis in human lymphoma B cells in vitro.

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.

Cell killing and mutation induction on Chinese hamster cells by photoradiations

International Nuclear Information System (INIS)

Lam, C.K.C.

1982-01-01

The subject matter of this investigation concerns the killing and mutagenic effects induced by far-UV radiation and broad spectra of black, white and gold lights. Applying radiation directly on CHO (Chinese hamster ovary) cells, far-UV is more effective than black light, and black light is more effective than white light in inducing proliferative death and in inducing resistance to 6-thioguanine (6TG), ouabain and diptheria toxin (DT). Cells in the G1/early S boundary are the most sensitive to far-UV or unfiltered fluorescent lights. When synchronous cells are irradiated with moderate doses of far-UV or unfiltered broad spectra of black light, mutations to 6-TG and ouabain resistance are slightly higher in early S period than in the remaining parts of the cell cycle. Mutation induction of 6-TG, ouabain or DT resistance is increased in the split-dose samples of the asynchronous and synchronous CHO cells. CHO cells predominantly express an error-prone repair mechanism after photoirradiation

Mechanisms involved in repairing the lesions induced in pBR 322 by PUVA treatment (8-Methoxypsoralen + ultraviolet A light)

International Nuclear Information System (INIS)

Bauluz, C.

1988-01-01

This work deals with the genotoxic effects derived from damaging pBR322 DNA through PUVA treatment (8-Methoxypsoralen plusUVA light), both with respect to the lethality and mutagenicity of the lesions produced by the treatment. The mechanisms involved in the repair of the plasmid lesions have been investigated by transforming several strains of E. coli differing in their DNA-repair capacities. The frequency, distribution and type of mutations occurring in a restriction fragment of the damaged plasmid were determined in order to establish the mutagenic features of the PUVA treatment. Damages produced bY PUVA habe a strong lethal effect on plasmid survival; however, partial recovery is possible through some of the bacterial DNA repair pathways, namely Excision repair, SOS-repair and a third mechanism which appears to be independent from the analised genes and is detected at high density of lesions per plasmid molecule. PUVA treatment produces a high increase in plasmid mutagenesis; however, the contribution of such an increase to the whole plasmid survival is negligible. Only punctual mutations were detected and consisted mainly in base-pair substitutions. Some mutation-prone regions were sound inside the investigated DNA fragment, a though their existence is more likely to be related with the structure acquired by the damaged DNA than with the type of damaging agent. (Author)

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.

Detection of induced male germline mutation: Correlations and comparisons between traditional germline mutation assays, transgenic rodent assays and expanded simple tandem repeat instability assays

Energy Technology Data Exchange (ETDEWEB)

Singer, Timothy M. [Mutagenesis Section, Environmental and Occupational Toxicology Division, Safe Environments Programme, 0803A, Health Canada, Ottawa, Ont., K1A 0K9 (Canada); Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, Ont., K1S 5B6 (Canada); Lambert, Iain B. [Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, Ont., K1S 5B6 (Canada); Williams, Andrew [Biostatistics and Epidemiology Division, Safe Environments Programme, 6604B, Health Canada, Ottawa, Ont., K1A 0K9 (Canada); Douglas, George R. [Mutagenesis Section, Environmental and Occupational Toxicology Division, Safe Environments Programme, 0803A, Health Canada, Ottawa, Ont., K1A 0K9 (Canada); Yauk, Carole L. [Mutagenesis Section, Environmental and Occupational Toxicology Division, Safe Environments Programme, 0803A, Health Canada, Ottawa, Ont., K1A 0K9 (Canada)]. E-mail: carole_yauk@hc-sc.gc.ca

2006-06-25

Several rodent assays are capable of monitoring germline mutation. These include traditional assays, such as the dominant lethal (DL) assay, the morphological specific locus (SL) test and the heritable translocation (HT) assay, and two assays that have been developed more recently-the expanded simple tandem repeat (ESTR) and transgenic rodent (TGR) mutation assays. In this paper, we have compiled the limited amount of experimental data that are currently available to make conclusions regarding the comparative ability of the more recently developed assays to detect germline mutations induced by chemical and radiological agents. The data suggest that ESTR and TGR assays are generally comparable with SL in detecting germline mutagenicity induced by alkylating agents and radiation, though TGR offered less sensitivity than ESTR in some cases. The DL and HT assays detect clastogenic events and are most susceptible to mutations arising in post-spermatogonial cells, and they may not provide the best comparisons with TGR and ESTR instability. The measurement of induced ESTR instability represents a relatively sensitive method of identifying agents causing germline mutation in rodents, and may also be useful for bio-monitoring exposed individuals in the human population. Any future use of the TGR and ESTR germline mutation assays in a regulatory testing context will entail more robust and extensive characterization of assay performance. This will require substantially more data, including experiments measuring multiple endpoints, a greatly expanded database of chemical agents and a focus on characterizing stage-specific activity of mutagens in these assays, preferably by sampling epididymal sperm exposed at defined pre-meiotic, meiotic and post-meiotic stages of development.

Detection of induced male germline mutation: Correlations and comparisons between traditional germline mutation assays, transgenic rodent assays and expanded simple tandem repeat instability assays

International Nuclear Information System (INIS)

Singer, Timothy M.; Lambert, Iain B.; Williams, Andrew; Douglas, George R.; Yauk, Carole L.

2006-01-01

Several rodent assays are capable of monitoring germline mutation. These include traditional assays, such as the dominant lethal (DL) assay, the morphological specific locus (SL) test and the heritable translocation (HT) assay, and two assays that have been developed more recently-the expanded simple tandem repeat (ESTR) and transgenic rodent (TGR) mutation assays. In this paper, we have compiled the limited amount of experimental data that are currently available to make conclusions regarding the comparative ability of the more recently developed assays to detect germline mutations induced by chemical and radiological agents. The data suggest that ESTR and TGR assays are generally comparable with SL in detecting germline mutagenicity induced by alkylating agents and radiation, though TGR offered less sensitivity than ESTR in some cases. The DL and HT assays detect clastogenic events and are most susceptible to mutations arising in post-spermatogonial cells, and they may not provide the best comparisons with TGR and ESTR instability. The measurement of induced ESTR instability represents a relatively sensitive method of identifying agents causing germline mutation in rodents, and may also be useful for bio-monitoring exposed individuals in the human population. Any future use of the TGR and ESTR germline mutation assays in a regulatory testing context will entail more robust and extensive characterization of assay performance. This will require substantially more data, including experiments measuring multiple endpoints, a greatly expanded database of chemical agents and a focus on characterizing stage-specific activity of mutagens in these assays, preferably by sampling epididymal sperm exposed at defined pre-meiotic, meiotic and post-meiotic stages of development

Petroleum distillates suppress in vitro metabolic activation: higher [S-9] required in the Salmonella/microsome mutagenicity assay.

Science.gov (United States)

Carver, J H; Machado, M L; MacGregor, J A

1985-01-01

To determine if standard conditions used in the Salmonella/mammalian microsome mutagenicity assay could reliably screen complex petroleum samples, two high-boiling (700-1,070 degrees F) distillates and their separated aromatic fractions were tested. The initial mutagenic activities were inconsistent with the samples' known polyaromatic hydrocarbon (PAH) contents and observed potencies in a dermal carcinogenesis bioassay. A significant mutagenic response was observed only at S-9 concentrations 5 to 10 times higher than those used in the standard assay, supporting the use of elevated levels of S-9 in the Salmonella/microsome assay to assess the carcinogenic potential of petroleum-derived materials. All four samples masked the expected mutagenic activity of added PAHs (benzo[a]pyrene and perylene). Data suggested that petroleum distillates suppress the functional efficacy of the S-9; possible mechanisms are discussed.

Mutagenic effect of radionuclides incorporated into DNA of Drosophila melanogaster. Progress report, 1975--1976

International Nuclear Information System (INIS)

Lee, W.R.

1976-01-01

Progress is reported on research in the following areas: determination of mutagenic effects of tritium incorporated into DNA using 32 P, 33 P, and 14 C; dosimetry studies using number of disintegrations per minute per sperm cell; effect of the 5-position of the label of the cytosine moiety on mutation frequency; distribution of labeled thymine and comparison with labeled cytosine and a non-DNA labeled arginine-rich protein; detection of temperature sensitive mutants; induction of mosaics by x radiation; and methods for determining quantitatively the location of tritium in the deoxycytidine moiety

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)

Induction of mutagenized tomato populations for investigation on agronomic traits and mutant phenotyping

Directory of Open Access Journals (Sweden)

Rafiul Amin Laskar

2018-01-01

Full Text Available Global demand for tomato production increased tremendously due to its diverse utility in raw, cooked and processed form of food. This necessitates the continued supply of highly nutritious and better yielding improved cultivars to the producers, considering the rapid changing agro-climatic condition. In this study, induced mutant tomato populations of widely recommended tomato genotype Arka Vikas (Sel-22 were generated using chemical mutagen ethyl methane sulfonate (EMS, hydrazine hydrates (HZ and their combined treatments. In the in vitro study, a gradual reduction in germination percentage and seedling height occurred with the increasing concentrations of mutagens. Combination of EMS and HZ caused maximum biological inhibition followed by EMS and HZ treatments alone in M1 generation. The rate of survival and fertility in M1 plants of tomato was found highly affected due to mutagenic treatment, in which sensitivity toward combined treatment was found highest followed by EMS and HZ. Inspection on induced phenotypic variations in individual plants of M2 population resulted in identification and isolation of wide range of mutants with altered phenotypes. Highest mutation frequency was resulted by combined mutagens followed by the EMS and HZ treatment. Agronomic trait analyses showed intra and inter treatment variations in three quantitative traits (Plant height, fertile branch per plant and fruits per plant of M2 mutagenized population. Assessment on rate of mutant recovery in M2 population showed highest mutant recovery is possible with combination treatments and then 0.02% HZ followed by 0.02% EMS. In the present study, phenotyping of the mutants revealed that vegetative organs (‘plant size’, ‘plant habit’ and ‘leaf morphology’ was the most sensitive category (69.33% to which most of the mutant belongs, followed by ‘fruit color and size’ (20.27% and ‘germination’ (9.79%. Comparative investigation on number of mutants and

Isolation and propagation of mutations by in vitro culture. Part of a coordinated programme on improvement of vegetatively propagated crops and tree crops through radiation induced mutations

International Nuclear Information System (INIS)

Asahira, T.

1974-01-01

Tuberous roots of two Dahlia cultivars were irradiated with 1000 - 2000 R of x-rays. Chlorophyll and flower colour mutations were scored on M 1 plants and the subsequent vegetatively propagated generations. The project aimed at the development of experimental methods suitable for easy isolation of mutated tissue chimeras deriving from mutagen treatment. In comparing in vivo methods such as leaf bud cutting and root propagation with in vitro methods using explants from leaves and florets, the problems encountered by in vitro culture were so manifold, that this method is not considered to be at present of much promise. These experimental results should not discourage from developing and using in vitro culture methods for mutant isolation in other plant species, particularly those were in vivo adventitious bud techniques are not available. Besides the main result obtained, the following valuable observations were made: a) The genotype used for mutation induction is not only relevant for the number and the spectrum of mutations, but also size of chimerical sectors. b) Flower colour changes, which were investigated in some detail, revealed that pigments were lost as groups e.g. all buteins in one case and all cyanins plus pelargonins in another case. c) When using the leaf bud cutting method the greatest frequency of mutations was recovered from the axillary bud of the leaf, that is at the youngest primordial stage at the time of mutagen treatment

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.

Sentinel and other mutational effects in offspring of cancer survivors

International Nuclear Information System (INIS)

Mulvihill, J.J.

1990-01-01

To date, no agent has been documented to cause germ cell mutation in human beings, with the possible exception of radiation causing abnormal meiotic chromosomes in testes. For studies in humans, mutation epidemiologists prefer the cohort approach, starting with an exposed population and looking for mutations that may be expressed in offspring as variants in health, chromosomes, proteins, or nucleic acids. Currently patients with cancer are the cohort exposed to the largest doses of potential mutagens, i.e., radiotherapy and drugs. In 12 large studies with over 825 patients and 1573 pregnancies, 46 (4%) of 1240 liveborns had a major birth defect, a rate comparable to that in the general population. One of these was a classic sentinel phenotype, i.e., a new sporadic case of a dominant mendelian syndrome. In collaboration with 5 U.S. cancer registries, we interviewed a retrospective cohort of 2383 patients diagnosed with cancer under age 20 years, from 1945 through 1975. Records were sought to verify major genetic disease, defined as a cytogenetic or single gene disorder or 1 of 15 isolated birth defects. In 2308 offspring of survivors, 5 had a chromosomal syndrome, 11 had a single gene disorder, and 62 had at least one major malformation. Among 4722 offspring of sibling controls, the respective numbers were 7, 12, and 127, nonsignificant differences. 7% of the parents of the offspring with possibly new mutations received potentially mutagenic therapy, compared with 12% of parents of normal children. Since pregnancy in or by cancer survivors is still a rare event, future efforts to document germ cell mutation may be best studied through international cooperation coupled with diverse laboratory measures of mutation

[Hygienic evaluation of the total mutagenic activity of snow samples from Magnitogorsk].

Science.gov (United States)

Legostaeva, T B; Ingel', F I; Antipanova, N A; Iurchenko, V V; Iuretseva, N A; Kotliar, N N

2010-01-01

The paper gives the results of 4-year monitoring of the total mutagenic activity of snow samples from different Magnitogork areas in a test for induction of dominant lethal mutations (DLM) in the gametes of Drosophila melanogaster. An association was first found between the rate of DLM and the content of some chemical compounds in the ambient air and snow samples; moreover all the substances present in the samples, which had found genotoxic effects, showed a positive correlation with the rate of DLM. Furthermore, direct correlations were first established between the rate of DLM and the air pollution index and morbidity rates in 5-7-year-old children residing in the areas under study. The findings allow the test for induction of dominant lethal mutations (DLM) in the gametes of Drosophila melanogaster to be recommended due to its unique informative and prognostic value for monitoring ambient air pollution and for extensive use in the risk assessment system.

Evaluation of the mutagenicity of alkylating agents, methylnitrosourea and temozolomide, using the rat Pig-a assay with total red blood cells or reticulocytes.

Science.gov (United States)

Muto, Shigeharu; Yamada, Katsuya; Kato, Tatsuya; Ando, Masamitsu; Inoue, Yoshimi; Iwase, Yumiko; Uno, Yoshifumi

2016-11-15

A collaborative study of the endogenous phosphatidylinositol glycan class A (Pig-a) gene mutation assay was conducted by the Japanese Environmental Mutagen Society/Mammalian Mutagenicity Study Group with a single-dosing regimen of test chemicals administered to male rats. As a part of the study, two DNA alkylating agents, methylnitrosourea (MNU) and temozolomide (TMZ), were dosed by single oral gavage at 25, 50, and 100mg/kg body weight. Pig-a mutant analysis of total red blood cells (RBCs; RBC Pig-a assay) and reticulocytes (RETs; PIGRET assay) was performed on Days 8, 15 and 29 after the administration. Both chemicals increased Pig-a mutants among RBCs and RETs with dose dependency on all days examined. The mutant frequencies were higher among RETs compared with RBCs, indicating that the PIGRET assay could detect mutagenicity more sensitively than the RBC Pig-a assay after a single dose of test chemicals. Copyright © 2016 Elsevier B.V. All rights reserved.

Detection of sodium azide-induced mutagenicity in the regenerated shoots of artemisia annual L., using internal transcribed spacer (its) sequences of nrDNA

International Nuclear Information System (INIS)

Al-Qurainy, F.; Al-Hemaidi, F.M.; Khan, S.; Ali, M.A.; Tarroum, M.; Ashraf, M.

2011-01-01

Sodium azide (NaN/sub 3/) is a well known chemical mutagen which can effectively cause point mutation in plant genome. The mutagenicity by this potential mutagen was assessed in the regenerated mutant shoots of Artemisia annua using internal transcribed spacer (ITS) sequences of n rDNA. Insertions and/or deletions were detected in n rDNA-ITS sequences of all mutant shoots and compared with control ones using the ClustalX program. The regenerated shoots TS1 and TS2 had deleted bases, whereas TS3, TS4 and TS5 had insertions, because NaN/sub 3/ replaced the cytosine (C) by thymine (T) (C - T) (shoots; TS1 and TS4) and thymine (T) replaced by guanine (G) (T - G) (shoot; TS5), respectively. Artemisinin content was also measured in the regenerated six-week-old shoots of A. annua. All regenerated shoots had enhanced level of this compound as compared to that in the controls, being highest in the regenerated shoot TS3. (author)

Expanded simple tandem repeat (ESTR) mutation induction in the male germline: Lessons learned from lab mice

Energy Technology Data Exchange (ETDEWEB)

Somers, Christopher M. [University of Regina, Department of Biology, 3737 Wascana Parkway, Regina, SK, S4S 0A2 (Canada)]. E-mail: chris.somers@uregina.ca

2006-06-25

Expanded simple tandem repeat (ESTR) DNA loci that are unstable in the germline have provided the most sensitive tool ever developed for investigating low-dose heritable mutation induction in laboratory mice. Ionizing radiation exposures have shown that ESTR mutations occur mainly in pre-meiotic spermatogonia and stem cells. The average spermatogonial doubling dose is 0.62-0.69 Gy for low LET, and 0.18-0.34 Gy for high LET radiation. Chemical alkylating agents also cause significant ESTR mutation induction in pre-meiotic spermatogonia and stem cells, but are much less effective per unit dose than radiation. ESTR mutation induction efficiency is maximal at low doses of radiation or chemical mutagens, and may decrease at higher dose ranges. DNA repair deficient mice (SCID and PARP-1) with elevated levels of single and double-strand DNA breaks have spontaneously elevated ESTR mutation frequencies, and surprisingly do not show additional ESTR mutation induction following irradiation. In contrast, ESTR mutation induction in p53 knock-outs is indistinguishable from that of wild-type mice. Studies of sentinel mice exposed in situ to ambient air pollution showed elevated ESTR mutation frequencies in males exposed to high levels of particulate matter. These studies highlight the application of the ESTR assay for assessing environmental hazards under real-world conditions. All ESTR studies to date have shown untargeted mutations that occur at much higher frequencies than predicted. The mechanism of this untargeted mutation induction is unknown, and must be elucidated before we can fully understand the biological significance of ESTR mutations, or use these markers for formal risk assessment. Future studies should focus on the mechanism of ESTR mutation induction, refining dose responses, and developing ESTR markers for other animal species.

Expanded simple tandem repeat (ESTR) mutation induction in the male germline: Lessons learned from lab mice

International Nuclear Information System (INIS)

Somers, Christopher M.

2006-01-01

Expanded simple tandem repeat (ESTR) DNA loci that are unstable in the germline have provided the most sensitive tool ever developed for investigating low-dose heritable mutation induction in laboratory mice. Ionizing radiation exposures have shown that ESTR mutations occur mainly in pre-meiotic spermatogonia and stem cells. The average spermatogonial doubling dose is 0.62-0.69 Gy for low LET, and 0.18-0.34 Gy for high LET radiation. Chemical alkylating agents also cause significant ESTR mutation induction in pre-meiotic spermatogonia and stem cells, but are much less effective per unit dose than radiation. ESTR mutation induction efficiency is maximal at low doses of radiation or chemical mutagens, and may decrease at higher dose ranges. DNA repair deficient mice (SCID and PARP-1) with elevated levels of single and double-strand DNA breaks have spontaneously elevated ESTR mutation frequencies, and surprisingly do not show additional ESTR mutation induction following irradiation. In contrast, ESTR mutation induction in p53 knock-outs is indistinguishable from that of wild-type mice. Studies of sentinel mice exposed in situ to ambient air pollution showed elevated ESTR mutation frequencies in males exposed to high levels of particulate matter. These studies highlight the application of the ESTR assay for assessing environmental hazards under real-world conditions. All ESTR studies to date have shown untargeted mutations that occur at much higher frequencies than predicted. The mechanism of this untargeted mutation induction is unknown, and must be elucidated before we can fully understand the biological significance of ESTR mutations, or use these markers for formal risk assessment. Future studies should focus on the mechanism of ESTR mutation induction, refining dose responses, and developing ESTR markers for other animal species

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.

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.

Acrolein- and 4-Aminobiphenyl-DNA adducts in human bladder mucosa and tumor tissue and their mutagenicity in human urothelial cells.

Science.gov (United States)

Lee, Hyun-Wook; Wang, Hsiang-Tsui; Weng, Mao-wen; Hu, Yu; Chen, Wei-sheng; Chou, David; Liu, Yan; Donin, Nicholas; Huang, William C; Lepor, Herbert; Wu, Xue-Ru; Wang, Hailin; Beland, Frederick A; Tang, Moon-shong

2014-06-15

Tobacco smoke (TS) is a major cause of human bladder cancer (BC). Two components in TS, 4-aminobiphenyl (4-ABP) and acrolein, which also are environmental contaminants, can cause bladder tumor in rat models. Their role in TS related BC has not been forthcoming. To establish the relationship between acrolein and 4-ABP exposure and BC, we analyzed acrolein-deoxyguanosine (dG) and 4-ABP-DNA adducts in normal human urothelial mucosa (NHUM) and bladder tumor tissues (BTT), and measured their mutagenicity in human urothelial cells. We found that the acrolein-dG levels in NHUM and BTT are 10-30 fold higher than 4-ABP-DNA adduct levels and that the acrolein-dG levels in BTT are 2 fold higher than in NHUM. Both acrolein-dG and 4-ABP-DNA adducts are mutagenic; however, the former are 5 fold more mutagenic than the latter. These two types of DNA adducts induce different mutational signatures and spectra. We found that acrolein inhibits nucleotide excision and base excision repair and induces repair protein degradation in urothelial cells. Since acrolein is abundant in TS, inhaled acrolein is excreted into urine and accumulates in the bladder and because acrolein inhibits DNA repair and acrolein-dG DNA adducts are mutagenic, we propose that acrolein is a major bladder carcinogen in TS.

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

Development of Trombay pulse crop varieties mutation through induced mutation

International Nuclear Information System (INIS)

Dhole, V.J.; Reddy, K.S.

2016-01-01

The food prices including pulses were beginning to increase from 2008, something that was not expected to happen before 2020. It was due to climate change, a scarcity of good arable land, water and nutrients. With these obstacles, we must produce almost double than what we are producing now to achieve food security by 2050. It can be achieved through crop improvement. Crop improvement is the art and science of changing the genetic make of crop plant in desire direction through various method of plant breeding. Mutation breeding is one of the techniques which utilize the physical and chemical mutagens to create genetic variability. Till date more than 3200 mutant varieties have been developed worldwide in which two physical mutagens i.e. X-rays and gamma rays have major contributions. Bhabha Atomic Research Centre is one of the leading institutes in India where nuclear energy is used for crop improvement, which resulted in to development of 43 improved high yielding varieties in different crops including 19 varieties of pulse crops. These varieties are contributing significantly to production of pulses and ultimately to national food security. (author)

Comparative in vitro and in vivo models of cytotoxicity and genotoxicity

International Nuclear Information System (INIS)

Brooks, A.L.; Mitchell, C.E.; Seiler, S.A.

1986-01-01

To understand the development of disease from inhalation of complex chemical mixtures, it is necessary to use both in vitro and whole animal systems. This project is designed to provide links between these two types of research. The project has three major goals. The first goal is to evaluate the mutagenic activity of complex mixtures and the interactions between different fractions in these mixtures. The second is to develop model cellular systems that help define the mechanisms of genotoxic damage and repair in the lung. The third goal is to understand the mechanisms involved in the induction of mutations and chromosome aberrations in mammalian cells. Research on the measurement and interactions of mutagens in complex mixtures is illustrated by reporting a study using diesel exhaust particle extracts. The extracts were fractionated into ten different chemical classes. Each of the fractions was tested for mutagenic activity in the Ames Salmonella mutation assay. Individual fractions were combined using different permutations. The total mixture was reconstituted and the mutagenic activity compared to the predicted level of activity. Mutagenic activity was additive indicating that the chemical fractionation did not alter the extracts and that there was little evidence of synergistic or antagonistic interaction. To help define the mechanisms involved in the induction of mutations, they have exposed CHO cells to radiation and mutagenic chemicals alone and in combination. In these studies, they have demonstrated that when cells were exposed to 500 rad of x-rays followed by either direct or indirect acting mutagens frequency was less than would be predicted by an additive model

Mechanisms of mutagenesis: DNA replication in the presence of DNA damage.

Science.gov (United States)

Liu, Binyan; Xue, Qizhen; Tang, Yong; Cao, Jia; Guengerich, F Peter; Zhang, Huidong

2016-01-01

Environmental mutagens cause DNA damage that disturbs replication and produces mutations, leading to cancer and other diseases. We discuss mechanisms of mutagenesis resulting from DNA damage, from the level of DNA replication by a single polymerase to the complex DNA replisome of some typical model organisms (including bacteriophage T7, T4, Sulfolobus solfataricus, Escherichia coli, yeast and human). For a single DNA polymerase, DNA damage can affect replication in three major ways: reducing replication fidelity, causing frameshift mutations, and blocking replication. For the DNA replisome, protein interactions and the functions of accessory proteins can yield rather different results even with a single DNA polymerase. The mechanism of mutation during replication performed by the DNA replisome is a long-standing question. Using new methods and techniques, the replisomes of certain organisms and human cell extracts can now be investigated with regard to the bypass of DNA damage. In this review, we consider the molecular mechanism of mutagenesis resulting from DNA damage in replication at the levels of single DNA polymerases and complex DNA replisomes, including translesion DNA synthesis. Copyright © 2016 Elsevier B.V. All rights reserved.

Improvement of rice varieties by induced mutations to increase yield per acre and resistance to diseases and to improve seed quality

Energy Technology Data Exchange (ETDEWEB)

Miah, A J; Bhatti, I M; Awan, A; Bari, G [Atomic Energy Agricultural Research Centre, Tandojam (Pakistan)

1970-03-01

Mutagen treatments of the variety Kangni-27 have given rise to short culm and early ripening strains. Experiments have been started with the varieties Dokri Basmati, Jajai-77, IR-8 and 370 Basmati using fast neutrons, gamma rays, EMS and dES as mutagens. Results obtained so far show a differential response of the varieties in their radiosensitivity and frequency of leaf colour mutations. (author)

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.

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.

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.

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

The role of radiation induced mutations in crop Improvement

International Nuclear Information System (INIS)

Souframanien, J.

2017-01-01

Sudden, heritable changes in the genetic material, DNA, are known as mutations. Selection of naturally occurring mutations in wild, ancestral species helped humans in the domestication and further improvement of today's crop plants. Gregor Mendel in 1865 used several such natural mutants in his experiments with garden pea to formulate the laws of inheritance. The term mutation itself was used for the first time by Hugo de Vries in 1901 in his mutation theory. Plant breeding based on the science of genetics, as practiced over the past 100 years, exploited the available genetic variability in the primary gene pool of crop plants, and sometimes in related species. Primarily, simple selection of desirable offspring and cross breeding were the earlier methods of breeding and this utilized the occurrence of spontaneous mutations. In nature, occurrence of natural variability in the form of spontaneous mutations is extremely low (about 10 -6 ), which can be enhanced several fold (∼10 -3 ) by using ionizing radiations or chemical mutagens

Induced mutations in castor

International Nuclear Information System (INIS)

Ganesan, K.; Javad Hussain, H.S.; Vindhiyavarman, P.

2001-01-01

Castor (Ricinus communis L.) is an important oilseed crop in India. To create variability mutations were induced in two cultivars 'TMV5' (maturing in 130-140 days) and 'CO1' (perennial type). Gamma rays and diethyl sulphate and ethidium bromide were used for seed treatment. Ten doses, from 100 to 1000 Gy were employed. For chemical mutagenesis five concentrations of mutagenes from 10 to 50 mM were tried. No economic mutants could be isolated after treatment with the chemical mutagens. The following economic mutants were identified in the dose 300 Gy of gamma rays. Annual types from perennial CO 1 castor CO 1 is a perennial variety (8-10 years) with bold seeds (100 seed weight 90 g) and high oil content (57%). Twenty-one lines were isolated with annual types (160-180 days) with high yield potential as well as bold seeds and high oil content. These mutants, identified in M 3 generation were bred true in subsequent generations up to M 8 generation. Critical evaluation of the mutants in yield evaluation trials is in progress

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.

Mechanism of SOS-induced targeted and untargeted mutagenesis in E. coli

International Nuclear Information System (INIS)

Maenhaut-Michel, G.

1985-01-01

This paper retraces the evolution of hypotheses concerning mechanisms of SOS induced mutagenesis. Moreover, it reports some recent data which support a new model for the mechanism of targeted and untargeted mutagenesis in E. coli. In summary, the SOS mutator effect, which is responsible for untargeted mutagenesis and perhaps for the misincorporation step in targeted mutagenesis, is believed to involve a fidelity function associated with DNA polymerase III and does not require the umuC gene product. umuC and umuD gene products are probably required specifically for elongation of DNA synthesis past blocking lesions, i.e. to allow mutagenic replication of damaged DNA

Mutation breeding in pepper

International Nuclear Information System (INIS)

Daskalov, S.

1986-01-01

Pepper (Capsicum sp.) is an important vegetable and spice crop widely grown in tropical as well as in temperate regions. Until recently the improvement programmes were based mainly on using natural sources of germ plasma, crossbreeding and exploiting the heterosis of F 1 hybrids. However, interest in using induced mutations is growing. A great number of agronomically useful mutants as well as mutants valuable for genetic, cytological and physiological studies have been induced and described. In this review information is presented about suitable mutagen treatment procedures with radiation as well as chemicals, M 1 effects, handling the treated material in M 1 , M 2 and subsequent generations, and mutant screening procedures. This is supplemented by a description of reported useful mutants and released cultivars. Finally, general advice is given on when and how to incorporate mutation induction in Capsicum improvement programmes. (author)

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.

The effects of extremely low frequency magnetic fields on mutation induction in mice

Energy Technology Data Exchange (ETDEWEB)

Wilson, James W. [Department of Genetics, University of Leicester, Leicester LE1 7RH (United Kingdom); Haines, Jackie; Sienkiewicz, Zenon [Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 0RQ (United Kingdom); Dubrova, Yuri E., E-mail: yed2@le.ac.uk [Department of Genetics, University of Leicester, Leicester LE1 7RH (United Kingdom)

2015-03-15

Highlights: • The effects of 50 Hz magnetic fields on mutation induction in mice were analyzed. • The frequency of ESTR mutation was established in sperm and blood. • Exposure to 10–300 μT for 2 and 15 h did not result in mutation induction. • Mutagenic effects of 50 Hz magnetic fields are likely to be negligible. - Abstract: The growing human exposure to extremely low frequency (ELF) magnetic fields has raised a considerable concern regarding their genotoxic effects. The aim of this study was to evaluate the in vivo effects of ELF magnetic fields irradiation on mutation induction in the germline and somatic tissues of male mice. Seven week old BALB/c × CBA/Ca F{sub 1} hybrid males were exposed to 10, 100 or 300 μT of 50 Hz magnetic fields for 2 or 15 h. Using single-molecule PCR, the frequency of mutation at the mouse Expanded Simple Tandem Repeat (ESTR) locus Ms6-hm was established in sperm and blood samples of exposed and matched sham-treated males. ESTR mutation frequency was also established in sperm and blood samples taken from male mice exposed to 1 Gy of acute X-rays. The frequency of ESTR mutation in DNA samples extracted from blood of mice exposed to magnetic fields did not significantly differ from that in sham-treated controls. However, there was a marginally significant increase in mutation frequency in sperm but this was not dose-dependent. In contrast, acute exposure X-rays led to significant increases in mutation frequency in sperm and blood of exposed males. The results of our study suggest that, within the range of doses analyzed here, the in vivo mutagenic effects of ELF magnetic fields are likely to be minor if not negligible.

The effects of extremely low frequency magnetic fields on mutation induction in mice

International Nuclear Information System (INIS)

Wilson, James W.; Haines, Jackie; Sienkiewicz, Zenon; Dubrova, Yuri E.

2015-01-01

Highlights: • The effects of 50 Hz magnetic fields on mutation induction in mice were analyzed. • The frequency of ESTR mutation was established in sperm and blood. • Exposure to 10–300 μT for 2 and 15 h did not result in mutation induction. • Mutagenic effects of 50 Hz magnetic fields are likely to be negligible. - Abstract: The growing human exposure to extremely low frequency (ELF) magnetic fields has raised a considerable concern regarding their genotoxic effects. The aim of this study was to evaluate the in vivo effects of ELF magnetic fields irradiation on mutation induction in the germline and somatic tissues of male mice. Seven week old BALB/c × CBA/Ca F 1 hybrid males were exposed to 10, 100 or 300 μT of 50 Hz magnetic fields for 2 or 15 h. Using single-molecule PCR, the frequency of mutation at the mouse Expanded Simple Tandem Repeat (ESTR) locus Ms6-hm was established in sperm and blood samples of exposed and matched sham-treated males. ESTR mutation frequency was also established in sperm and blood samples taken from male mice exposed to 1 Gy of acute X-rays. The frequency of ESTR mutation in DNA samples extracted from blood of mice exposed to magnetic fields did not significantly differ from that in sham-treated controls. However, there was a marginally significant increase in mutation frequency in sperm but this was not dose-dependent. In contrast, acute exposure X-rays led to significant increases in mutation frequency in sperm and blood of exposed males. The results of our study suggest that, within the range of doses analyzed here, the in vivo mutagenic effects of ELF magnetic fields are likely to be minor if not negligible

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.

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

Effects of Mutagen-Sensitive Mus Mutations on Spontaneous Mitotic Recombination in Aspergillus

OpenAIRE

Zhao, P.; Kafer, E.

1992-01-01

Methyl methane-sulfonate (MMS)-sensitive, radiation-induced mutants of Aspergillus were shown to define nine new DNA repair genes, musK to musS. To test mus mutations for effects on mitotic recombination, intergenic crossing over was assayed between color markers and their centromeres, and intragenic recombination between two distinguishable adE alleles. Of eight mutants analyzed, four showed significant deviations from mus(+) controls in both tests. Two mutations, musK and musL, reduced reco...

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).

Induced mutations for crop improvement

International Nuclear Information System (INIS)

Micke, A.; Donini, B.; Maluszynski, M.

1990-01-01

Mutation induction has become an established tool in plant breeding to supplement existing germ plasma and to improve cultivars in certain specific traits. Hundreds of improved varieties have been released to farmers for many different crop species, demonstrating the economic value of the technology. Limitations arise mainly from the large mutagenized populations to be screened and from the unsatisfactory selection methods. Both limitations may be eased to some extent by advances in techniques of plant in-vitro culture. (author). Refs, 1 fig., 7 tabs

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...

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.

Mutation breeding in jute

International Nuclear Information System (INIS)

Joshua, D.C.

1980-01-01

Mutagenic studies in jute in general dealt with the morphological abnormalities of the M 1 generation in great detail. Of late, induction of a wide spectrum of viable mutations have been reported in different varieties of both the species. Mutations affecting several traits of agronomic importance such as, plant height, time of flowering, fibre yield and quality, resistance to pests and diseases are also available. Cytological analysis of a large collection of induced mutants resulted in the isolation of seven trisomics in an olitorius variety. Several anatomical parameters which are the components of fibre yield, have also received attention. Some mutants with completely altered morphology were used for interpreting the evolution of leaf shape in Tiliaceas and related families. A capsularis variety developed using mutation breeding technique has been released for cultivation. Several others, including derivatives of inter-mutant hybridization have been found to perform well at different locations in the All India Coordinated Trials. Presently, chemical mutagenesis and induction of mutants of physiological significance are receiving considerable attention. The induced variability is being used in genetic and linkage studies. (author)

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.

Mutation breeding in crop improvement - achievements and prospects

International Nuclear Information System (INIS)

Kharkwal, M.C.

2004-01-01

Crop improvement programmes through induced mutations were initiated about seven decades ago. Majority of the mutant varieties have been released during the last two decades. In terms of the development and release of mutant varieties, China (605), India (309), Russia (204), the Netherlands (176), USA (125) and Japan (120) are the leading countries. Radiation, especially gamma radiation was the most frequently used mutagen for inducing mutations in crop plants. Out of 1072 mutant varieties of cereals, rice alone accounts for 434 varieties followed by barley (269). Mutation breeding has made significant contribution in increasing the production of rice, ground nut, castor, chickpea, mungbean and urd bean in the Indian subcontinent. The future mutation breeding programmes should be aimed at improving the root characters, nodulation in legumes, alteration of fatty acid composition in oil seeds, host pathogen interactions, photo- insensitivity and apomixix in crop plants

The effect of point mutations on structure and mechanical properties of collagen-like fibril: A molecular dynamics study

International Nuclear Information System (INIS)

Marlowe, Ashley E.; Singh, Abhishek; Yingling, Yaroslava G.

2012-01-01

Understanding sequence dependent mechanical and structural properties of collagen fibrils is important for the development of artificial biomaterials for medical and nanotechnological applications. Moreover, point mutations are behind many collagen associated diseases, including Osteogenesis Imperfecta (OI). We conducted a combination of classical and steered atomistic molecular dynamics simulations to examine the effect of point mutations on structure and mechanical properties of short collagen fibrils which include mutations of glycine to alanine, aspartic acid, cysteine, and serine or mutations of hydroxyproline to arginine, asparagine, glutamine, and lysine. We found that all mutations disrupt structure and reduce strength of the collagen fibrils, which may affect the hierarchical packing of the fibrils. The glycine mutations were more detrimental to mechanical strength of the fibrils (WT > Ala > Ser > Cys > Asp) than that of hydroxyproline (WT > Arg > Gln > Asn > Lys). The clinical outcome for glycine mutations agrees well with the trend in reduction of fibril's tensile strength predicted by our simulations. Overall, our results suggest that the reduction in mechanical properties of collagen fibrils may be used to predict the clinical outcome of mutations. Highlights: ► All mutations disrupt structure and bonding pattern and reduce strength of the collagen fibrils. ► Gly based mutations are worst to mechanical integrity of fibrils than that of Hyp. ► Lys and Arg mutations most dramatically destabilize collagen fibril properties. ► Clinical outcome of mutations may be related to the reduced mechanical properties of fibrils.

Molecular methods for the detection of mutations.

Science.gov (United States)

Monteiro, C; Marcelino, L A; Conde, A R; Saraiva, C; Giphart-Gassler, M; De Nooij-van Dalen, A G; Van Buuren-van Seggelen, V; Van der Keur, M; May, C A; Cole, J; Lehmann, A R; Steinsgrimsdottir, H; Beare, D; Capulas, E; Armour, J A

2000-01-01

We report the results of a collaborative study aimed at developing reliable, direct assays for mutation in human cells. The project used common lymphoblastoid cell lines, both with and without mutagen treatment, as a shared resource to validate the development of new molecular methods for the detection of low-level mutations in the presence of a large excess of normal alleles. As the "gold standard, " hprt mutation frequencies were also measured on the same samples. The methods under development included i) the restriction site mutation (RSM) assay, in which mutations lead to the destruction of a restriction site; ii) minisatellite length-change mutation, in which mutations lead to alleles containing new numbers of tandem repeat units; iii) loss of heterozygosity for HLA epitopes, in which antibodies can be used to direct selection for mutant cells; iv) multiple fluorescence-based long linker arm nucleotides assay (mf-LLA) technology, for the detection of substitutional mutations; v) detection of alterations in the TP53 locus using a (CA) array as the target for the screening; and vi) PCR analysis of lymphocytes for the presence of the BCL2 t(14:18) translocation. The relative merits of these molecular methods are discussed, and a comparison made with more "traditional" methods.

Lack of mutational hot spots during decitabine-mediated HIV-1 mutagenesis.

Science.gov (United States)

Rawson, Jonathan M O; Landman, Sean R; Reilly, Cavan S; Bonnac, Laurent; Patterson, Steven E; Mansky, Louis M

2015-11-01

Decitabine has previously been shown to induce lethal mutagenesis of human immunodeficiency virus type 1 (HIV-1). However, the factors that determine the susceptibilities of individual sequence positions in HIV-1 to decitabine have not yet been defined. To investigate this, we performed Illumina high-throughput sequencing of multiple amplicons prepared from proviral DNA that was recovered from decitabine-treated cells infected with HIV-1. We found that decitabine induced an ≈4.1-fold increase in the total mutation frequency of HIV-1, primarily due to a striking ≈155-fold increase in the G-to-C transversion frequency. Intriguingly, decitabine also led to an ≈29-fold increase in the C-to-G transversion frequency. G-to-C frequencies varied substantially (up to ≈80-fold) depending upon sequence position, but surprisingly, mutational hot spots (defined as upper outliers within the mutation frequency distribution) were not observed. We further found that every single guanine position examined was significantly susceptible to the mutagenic effects of decitabine. Taken together, these observations demonstrate for the first time that decitabine-mediated HIV-1 mutagenesis is promiscuous and occurs in the absence of a clear bias for mutational hot spots. These data imply that decitabine-mediated G-to-C mutagenesis is a highly effective antiviral mechanism for extinguishing HIV-1 infectivity. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Discovering human germ cell mutagens with whole genome sequencing: Insights from power calculations reveal the importance of controlling for between-family variability.

Science.gov (United States)

Webster, R J; Williams, A; Marchetti, F; Yauk, C L

2018-07-01

Mutations in germ cells pose potential genetic risks to offspring. However, de novo mutations are rare events that are spread across the genome and are difficult to detect. Thus, studies in this area have generally been under-powered, and no human germ cell mutagen has been identified. Whole Genome Sequencing (WGS) of human pedigrees has been proposed as an approach to overcome these technical and statistical challenges. WGS enables analysis of a much wider breadth of the genome than traditional approaches. Here, we performed power analyses to determine the feasibility of using WGS in human families to identify germ cell mutagens. Different statistical models were compared in the power analyses (ANOVA and multiple regression for one-child families, and mixed effect model sampling between two to four siblings per family). Assumptions were made based on parameters from the existing literature, such as the mutation-by-paternal age effect. We explored two scenarios: a constant effect due to an exposure that occurred in the past, and an accumulating effect where the exposure is continuing. Our analysis revealed the importance of modeling inter-family variability of the mutation-by-paternal age effect. Statistical power was improved by models accounting for the family-to-family variability. Our power analyses suggest that sufficient statistical power can be attained with 4-28 four-sibling families per treatment group, when the increase in mutations ranges from 40 to 10% respectively. Modeling family variability using mixed effect models provided a reduction in sample size compared to a multiple regression approach. Much larger sample sizes were required to detect an interaction effect between environmental exposures and paternal age. These findings inform study design and statistical modeling approaches to improve power and reduce sequencing costs for future studies in this area. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Genome-wide analysis of mutations in mutant lineages selected following fast-neutron irradiation mutagenesis of Arabidopsis thaliana

KAUST Repository

Belfield, E.J.; Gan, X.; Mithani, A.; Brown, C.; Jiang, C.; Franklin, K.; Alvey, E.; Wibowo, A.; Jung, M.; Bailey, K.; Kalwani, S.; Ragoussis, J.; Mott, R.; Harberd, N.P.

2012-01-01

Ionizing radiation has long been known to induce heritable mutagenic change in DNA sequence. However, the genome-wide effect of radiation is not well understood. Here we report the molecular properties and frequency of mutations in phenotypically selected mutant lines isolated following exposure of the genetic model flowering plant Arabidopsis thaliana to fast neutrons (FNs). Previous studies suggested that FNs predominantly induce deletions longer than a kilobase in A. thaliana. However, we found a higher frequency of single base substitution than deletion mutations. While the overall frequency and molecular spectrum of fast-neutron (FN)-induced single base substitutions differed substantially from those of "background" mutations arising spontaneously in laboratory-grown plants, G:C>A:T transitions were favored in both. We found that FN-induced G:C>A:T transitions were concentrated at pyrimidine dinucleotide sites, suggesting that FNs promote the formation of mutational covalent linkages between adjacent pyrimidine residues. In addition, we found that FNs induced more single base than large deletions, and that these single base deletions were possibly caused by replication slippage. Our observations provide an initial picture of the genome-wide molecular profile of mutations induced in A. thaliana by FN irradiation and are particularly informative of the nature and extent of genome-wide mutation in lines selected on the basis of mutant phenotypes from FN-mutagenized A. thaliana populations.

Genome-wide analysis of mutations in mutant lineages selected following fast-neutron irradiation mutagenesis of Arabidopsis thaliana

KAUST Repository

Belfield, E.J.

2012-04-12

Ionizing radiation has long been known to induce heritable mutagenic change in DNA sequence. However, the genome-wide effect of radiation is not well understood. Here we report the molecular properties and frequency of mutations in phenotypically selected mutant lines isolated following exposure of the genetic model flowering plant Arabidopsis thaliana to fast neutrons (FNs). Previous studies suggested that FNs predominantly induce deletions longer than a kilobase in A. thaliana. However, we found a higher frequency of single base substitution than deletion mutations. While the overall frequency and molecular spectrum of fast-neutron (FN)-induced single base substitutions differed substantially from those of "background" mutations arising spontaneously in laboratory-grown plants, G:C>A:T transitions were favored in both. We found that FN-induced G:C>A:T transitions were concentrated at pyrimidine dinucleotide sites, suggesting that FNs promote the formation of mutational covalent linkages between adjacent pyrimidine residues. In addition, we found that FNs induced more single base than large deletions, and that these single base deletions were possibly caused by replication slippage. Our observations provide an initial picture of the genome-wide molecular profile of mutations induced in A. thaliana by FN irradiation and are particularly informative of the nature and extent of genome-wide mutation in lines selected on the basis of mutant phenotypes from FN-mutagenized A. thaliana populations.

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.

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

Effects of mutagen-sensitive mus mutations on spontaneous mitotic recombination in Aspergillus.

Science.gov (United States)

Zhao, P; Kafer, E

1992-04-01

Methyl methane-sulfonate (MMS)-sensitive, radiation-induced mutants of Aspergillus were shown to define nine new DNA repair genes, musK to musS. To test mus mutations for effects on mitotic recombination, intergenic crossing over was assayed between color markers and their centromeres, and intragenic recombination between two distinguishable adE alleles. Of eight mutants analyzed, four showed significant deviations from mus+ controls in both tests. Two mutations, musK and musL, reduced recombination, while musN and musQ caused increases. In contrast, musO diploids produced significantly higher levels only for intragenic recombination. Effects were relatively small, but averages between hypo- and hyperrec mus differed 15-20-fold. In musL diploids, most of the rare color segregants resulted from mitotic malsegregation rather than intergenic crossing over. This indicates that the musL gene product is required for recombination and that DNA lesions lead to chromosome loss when it is deficient. In addition, analysis of the genotypes of intragenic (ad+) recombinants showed that the musL mutation specifically reduced single allele conversion but increased complex conversion types (especially recombinants homozygous for ad+). Similar analysis revealed differences between the effects of two hyperrec mutations; musN apparently caused high levels solely of mitotic crossing over, while musQ increased various conversion types but not reciprocal crossovers. These results suggest that mitotic gene conversion and crossing over, while generally associated, are affected differentially in some of the mus strains of Aspergillus nidulans.

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.

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

Use of embryogenic cell suspension and meristem-tip cultures for mutation breeding of apomictic Musa species

International Nuclear Information System (INIS)

Novak, F.J.; Afza, R.; Duren, M. van

1990-01-01

Full text: Breeding by crossing is difficult for banana and plantain. The plants are heterozygous, therefore mutagenic treatment may uncover a recessive allele by mutating or deleting a corresponding dominant allele. Meristem tips were excised from in vitro growing shoots and used for mutation experiments. Induction was carried out by irradiating shoot tips with γ rays and/or by treatment of explants with ethylmethanesulfonate (EMS). Cell suspension was initiated from corm and leaf tissue excised from in vitro grown plantlets. Mutagenised cell suspensions were derived from leaf and corm tissues irradiated with 60 Co γ rays - (10 to 60 Gy, 8 Gy/min). Musa clones exhibited differences in radiosensitivity and post-irradiation recovery. Doses of 20 to 40 Gy seem suitable for mutation induction. The EMS concentration of 25 mM for 4 hours was found effective for isolated shoot tips. Considerable phenotypic variation was observed among plants regenerated from in vitro shoot tips after mutagenic treatment. Leaf and corm explants kept their morphogenic ability in embryogenic cell suspensions after irradiation up to 25 Gy. (author)

EFFECT OF GAMMA RADIATION OF MACRO MUTATIONS, EFFECTIVENESS AND EFFICIENCY UNDER M2 GENERATION IN PEA (Pisum sativum L.

Directory of Open Access Journals (Sweden)

Arvind KUMAR

2016-06-01

Full Text Available The present investigation was undertaken to study the spectrum of macro mutants, effectiveness and efficiency of different doses of gamma rays in pea variety (Arkel. The seeds were treated with gamma rays viz., 00kR (dry control, 05kR, 10kR, 15kR, 20kR, 25kR, 30kR, 35kR, 40kR (dry seeds and presoaked seeds of the same was exposed to 00kR (wet control, 05kR, 10kR, 15kR, 20kR (kilo Roentgen biological damage was calculated in M1 and M2 generation based on lethality (L and pollen sterility. The irradiated seeds were sown in the M1 field their respective controls and harvested in bulk to raise the M2 generation in Randomized Block Design (RBD with three replications. The spectrum of macro mutants i.e., plant stature (tall, dwarf, small dwarf, maturity (early, late, pod shape (bold, long, short, seed colour (brown, light white, light green and seed shape (small, bold, wrinkled were observed in M2 generation. The usefulness of any mutagen in plant breeding depends not only on its effectiveness but also upon if efficiency. Mutagenic effectiveness is a measure of the frequency of mutations induced by unit mutagen dose, whereas mutagenic efficiency is measure of proportion of mutations in relation of undesirable changes like lethality and sterility are used for gamma rays. A result of the indicated positive relationship in M2 generation with macro mutation, effectiveness and efficiency was found to be highest at lowest doses.

Charged-particle mutagenesis II. Mutagenic effects of high energy charged particles in normal human fibroblasts

Science.gov (United States)

Chen, D. J.; Tsuboi, K.; Nguyen, T.; Yang, T. C.

1994-01-01

The biological effects of high LET charged particles are a subject of great concern with regard to the prediction of radiation risk in space. In this report, mutagenic effects of high LET charged particles are quantitatively measured using primary cultures of human skin fibroblasts, and the spectrum of induced mutations are analyzed. The LET of the charged particles ranged from 25 KeV/micrometer to 975 KeV/micrometer with particle energy (on the cells) between 94-603 MeV/u. The X-chromosome linked hypoxanthine guanine phosphoribosyl transferase (hprt) locus was used as the target gene. Exposure to these high LET charged particles resulted in exponential survival curves; whereas, mutation induction was fitted by a linear model. The Relative Biological Effect (RBE) for cell-killing ranged from 3.73 to 1.25, while that for mutant induction ranged from 5.74 to 0.48. Maximum RBE values were obtained at the LET of 150 keV/micrometer. The inactivation cross-section (alpha i) and the action cross-section for mutant induction (alpha m) ranged from 2.2 to 92.0 micrometer2 and 0.09 to 5.56 x 10(-3) micrometer2, respectively. The maximum values were obtained by 56Fe with an LET of 200 keV/micrometer. The mutagenicity (alpha m/alpha i) ranged from 2.05 to 7.99 x 10(-5) with the maximum value at 150 keV/micrometer. Furthermore, molecular analysis of mutants induced by charged particles indicates that higher LET beams are more likely to cause larger deletions in the hprt locus.

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

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

International Nuclear Information System (INIS)

Seetharam, S.; Protic-Sabljic, M.; Seidman, M.M.; Kraemer, K.H.

1987-01-01

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

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)

Anti-mutagenic and Pro-apoptotic Effects of Apigenin on Human Chronic Lymphocytic Leukemia Cells

Directory of Open Access Journals (Sweden)

Mehrdad Hashemi

2010-10-01

Full Text Available Diet can play a vital role in cancer prevention. Nowadays the scientists are looking for food materials which can potentially prevent the cancer occurrence. The purpose of this research is to examine anti-mutagenic and apoptotic effects of apigenin in human lymphoma cells. In present study human chronic lymphocytic leukemia (Eheb cell line were cultured in RPMI 1640 (Sigma, supplemented with 10% fetal calf serum, penicillin-streptomycin, L-glutamine and incubated at 37 ºC for 2 days. In addition cancer cell line was treated by and apigenin and cellular vital capacity was determined by MTT assay. Then effect of apigenin in human lymphoma B cells was examined by flow cytometry techniques. The apigenin was subsequently evaluated in terms of anti-mutagenic properties by a standard reverse mutation assay (Ames test. This was performed with histidine auxotroph strain of Salmonella typhimurium (TA100. Thus, it requires histidine from a foreign supply to ensure its growth. The aforementioned strain gives rise to reverted colonies when expose to sodium azide as a carcinogen substance. During MTT assay, human chronic lymphocytic leukemia revealed to have a meaningful cell death when compared with controls (P

Tissue-specific metabolic activation and mutagenicity of 3-nitrobenzanthrone in MutaMouse.

Science.gov (United States)

Chen, Guosheng; Gingerich, John; Soper, Lynda; Douglas, George R; White, Paul A

2008-10-01

3-Nitrobenzanthrone (3-NBA) is a mutagen and suspected human carcinogen detected in diesel exhaust, airborne particulate matter, and urban soil. We investigated the tissue specific mutagenicity of 3-NBA at the lacZ locus of transgenic MutaMouse following acute single dose or 28-day repeated-dose oral administration. In the acute high dose (50 mg/kg) exposure, increased lacZ mutant frequency was observed in bone marrow and colonic epithelium, but not in liver and bladder. In the repeated-dose study, a dose-dependent increase in lacZ mutant frequency was observed in bone marrow and liver (2- and 4-fold increase above control), but not in lung or intestinal epithelium. In addition, a concentration-dependent increase in mutant frequency (8.5-fold above control) was observed for MutaMouse FE1 lung epithelial cells exposed in vitro. 1-Nitropyrene reductase, 3-NBA reductase, and acetyltransferase activities were measured in a variety of MutaMouse specimens in an effort to link metabolic activation and mutagenicity. High 3-NBA nitroreductase activities were observed in lung, liver, colon and bladder, and detectable N-acetyltransferase activities were found in all tissues except bone marrow. The relatively high 3-NBA nitroreductase activity in MutaMouse tissues, as compared with those in Salmonella TA98 and TA100, suggests that 3-NBA is readily reduced and activated in vivo. High 3-NBA nitroreductase levels in liver and colon are consistent with the elevated lacZ mutant frequency values, and previously noted inductions of hepatic DNA adducts. Despite an absence of induced lacZ mutations, the highest 3-NBA reductase activity was detected in lung. Further studies are warranted, especially following inhalation or intratracheal exposures. Published 2008 Wiley-Liss, Inc.

Comparative studies on the lethal, mutagenic, and recombinogenic effects of ultraviolet -A, -B, -C, and visible light with and without 8-methoxypsoralen in Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Mondon, P.; Shahin, M.M.

1992-01-01

Genetic effects of UV-A, UV-B, UV-C and the combination of 8-methoxypsoralen (8-MOP) with UV-A or visible light were studied in the haploid strain XV185-14C and diploid strain D5 of Saccharomyces cerevisiae. The induction of his + , lys + , and hom + reverse mutations was measured in strain XV185-14C. In strain D5 we measured the induction of genetically altered colonies, particularly twin spot colonies arising from a mitotic crossing-over. UV-C and UV-B induced point mutations at the three loci in the haploid strain and mitotic crossing-over and other genetic alterations in the diploid strain. UV-C was more mutagenic and recombinogenic than UV-B. UV-A or visible light alone did not induce genotoxic effects at the doses tested. However, UV-A plus 8-MOP produced lethal and mutagenic effects in the haploid strain XV185-14C, although mutagenic activity was less than that of UV-B. Visible light plus 8-MOP also induced genotoxic effects in strain XV185-14C. In the diploid strain D5, UV-A plus 8-MOP induced a higher frequency of genetic alterations than UV-B at comparative doses. Visible light plus 8-MOP was also genetically active in strain D5. The haploid strain was more sensitive to the lethal effects of UV-C, UV-B, UV-A, and impure visible light plus 8-MOP than the diploid strain. (Author)

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

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.

The effect of point mutations on structure and mechanical properties of collagen-like fibril: A molecular dynamics study

Energy Technology Data Exchange (ETDEWEB)

Marlowe, Ashley E.; Singh, Abhishek; Yingling, Yaroslava G., E-mail: yara_yingling@ncsu.edu

2012-12-01

Understanding sequence dependent mechanical and structural properties of collagen fibrils is important for the development of artificial biomaterials for medical and nanotechnological applications. Moreover, point mutations are behind many collagen associated diseases, including Osteogenesis Imperfecta (OI). We conducted a combination of classical and steered atomistic molecular dynamics simulations to examine the effect of point mutations on structure and mechanical properties of short collagen fibrils which include mutations of glycine to alanine, aspartic acid, cysteine, and serine or mutations of hydroxyproline to arginine, asparagine, glutamine, and lysine. We found that all mutations disrupt structure and reduce strength of the collagen fibrils, which may affect the hierarchical packing of the fibrils. The glycine mutations were more detrimental to mechanical strength of the fibrils (WT > Ala > Ser > Cys > Asp) than that of hydroxyproline (WT > Arg > Gln > Asn > Lys). The clinical outcome for glycine mutations agrees well with the trend in reduction of fibril's tensile strength predicted by our simulations. Overall, our results suggest that the reduction in mechanical properties of collagen fibrils may be used to predict the clinical outcome of mutations. Highlights: Black-Right-Pointing-Pointer All mutations disrupt structure and bonding pattern and reduce strength of the collagen fibrils. Black-Right-Pointing-Pointer Gly based mutations are worst to mechanical integrity of fibrils than that of Hyp. Black-Right-Pointing-Pointer Lys and Arg mutations most dramatically destabilize collagen fibril properties. Black-Right-Pointing-Pointer Clinical outcome of mutations may be related to the reduced mechanical properties of fibrils.

Mutagenesis: Interactions with a parallel universe.

Science.gov (United States)

Miller, Jeffrey H

Unexpected observations in mutagenesis research have led to a new perspective in this personal reflection based on years of studying mutagenesis. Many mutagens have been thought to operate via a single principal mechanism, with secondary effects usually resulting in only minor changes in the observed mutation frequencies and spectra. For example, we conceive of base analogs as resulting in direct mispairing as their main mechanism of mutagenesis. Recent studies now show that in fact even these simple mutagens can cause very large and unanticipated effects both in mutation frequencies and in the mutational spectra when used in certain pair-wise combinations. Here we characterize this leap in mutation frequencies as a transport to an alternate universe of mutagenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

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

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

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.

Mutation breeding in pepper

Energy Technology Data Exchange (ETDEWEB)

Daskalov, S [Plant Breeding Unit, Joint FAO/IAEA Division of Isotope and Radiation Applications of Atomic Energy for Food and Agricultural Development, Seibersdorf Laboratory, International Atomic Energy Agency, Vienna (Austria)

1986-03-01

Pepper (Capsicum sp.) is an important vegetable and spice crop widely grown in tropical as well as in temperate regions. Until recently the improvement programmes were based mainly on using natural sources of germ plasma, crossbreeding and exploiting the heterosis of F{sub 1} hybrids. However, interest in using induced mutations is growing. A great number of agronomically useful mutants as well as mutants valuable for genetic, cytological and physiological studies have been induced and described. In this review information is presented about suitable mutagen treatment procedures with radiation as well as chemicals, M{sub 1} effects, handling the treated material in M{sub 1}, M{sub 2} and subsequent generations, and mutant screening procedures. This is supplemented by a description of reported useful mutants and released cultivars. Finally, general advice is given on when and how to incorporate mutation induction in Capsicum improvement programmes. (author)

[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.

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.

Plant Breeding by Using Radiation Mutation

International Nuclear Information System (INIS)

Kang, Si Yong; Kim, Dong Sub; Lee, Geung Joo

2007-06-01

A mutation breeding is to use physical or chemical mutagens to induce mutagenesis, followed by individual selections with favorable traits. The mutation breeding has many advantages over other breeding methods, which include the usefulness for improving one or two inferior characteristics, applications to broad species with different reproductive systems or to diverse plant materials, native or plant introduction with narrow genetic background, time and cost-effectiveness, and valuable mutant resources for genomic researches. Recent applications of the radiation breeding techniques to developments of flowering plants or food crops with improved functional constituents heightened the public's interests in agriculture and in our genetic resources and seed industries. The goals of this project, therefore, include achieving advances in domestic seed industries and agricultural productivities by developing and using new radiation mutants with favored traits, protecting an intellectual property right of domestic seeds or germplasm, and sharing the valuable mutants and mutated gene information for the genomic and biotech researches that eventually leads to economic benefits

Plant Breeding by Using Radiation Mutation

Energy Technology Data Exchange (ETDEWEB)

Kang, Si Yong; Kim, Dong Sub; Lee, Geung Joo (and others)

2007-06-15

A mutation breeding is to use physical or chemical mutagens to induce mutagenesis, followed by individual selections with favorable traits. The mutation breeding has many advantages over other breeding methods, which include the usefulness for improving one or two inferior characteristics, applications to broad species with different reproductive systems or to diverse plant materials, native or plant introduction with narrow genetic background, time and cost-effectiveness, and valuable mutant resources for genomic researches. Recent applications of the radiation breeding techniques to developments of flowering plants or food crops with improved functional constituents heightened the public's interests in agriculture and in our genetic resources and seed industries. The goals of this project, therefore, include achieving advances in domestic seed industries and agricultural productivities by developing and using new radiation mutants with favored traits, protecting an intellectual property right of domestic seeds or germplasm, and sharing the valuable mutants and mutated gene information for the genomic and biotech researches that eventually leads to economic benefits.

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.)

Induction of mutations in the blue-green alga Plectonema boryanum Gomont

International Nuclear Information System (INIS)

Singh, R.N.; Kashyap, A.K.

1977-01-01

Mutations to cyanophage and streptomycin resistance were induced in the filamentous blue-gree alga Plectonema boryanum IU 594 after treatment with ultraviolet irradiation, N-methyl-N'-nitro-Nnitrosoguanidine, acriflavine, 2-aminopurine and caffeine. Phage-resistant mutants were obtained with all the mutagens tested. Their efficiencies were in the order: MNNG>UV>acriflavine >2-AP>caffeine. In contrast, the drug-resistant mutants were not induced by base analogues: the efficiencies were: acriflavine>MNNG>UV. Lethal and mutational lesions induced with UV were efficiently repaired under photo-reactivating conditions whereas post-treatment with caffeine resulted in enhanced mutation frequencies especially at low UV doses. Neither survival nor mutagenesis was enhanced by keeping the MNNG-treated population in subdued light

Analysis of genotoxic activity of ketamine and rocuronium bromide using the somatic mutation and recombination test in Drosophila melanogaster.

Science.gov (United States)

Koksal, Pakize Muge; Gürbüzel, Mehmet

2015-03-01

The present study evaluated the mutagenic and recombinogenic effects of two commonly used anesthetic agents, ketamine and rocuronium bromide, in medicine using the wing somatic mutation and recombination test (SMART) in Drosophila. The standard (ST) cross and the high-bioactivation (HB) cross with high sensitivity to procarcinogens and promutagens were used. The SMART test is based on the loss of heterozygosity, which occurs via various mechanisms, such as chromosome loss and deletion, half-translocation, mitotic recombination, mutation, and non-disjunction. Genetic alterations occurring in the somatic cells of the wing's imaginal discs result in mutant clones in the wing blade. Three-day-old trans-heterozygous larvae with two recessive markers, multiple wing hairs (mwh) and flare (flr(3)), were treated with ketamine and rocuronium bromide. Analysis of the ST cross indicated that ketamine exhibited genotoxicity activity and that this activity was particularly dependent on homologous mitotic recombination at concentrations of 250 μg/ml and above. Rocuronium bromide did not exert mutagenic and/or recombinogenic effects. In the HB cross, ketamine at a concentration of 1000 μg/ml and rocuronium bromide at all concentrations, with the exception of 250 μg/ml (inconclusive), exerted genotoxic effects, which could also be associated with the increase in mitotic recombination. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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

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.

Survival and mutagenesis in UV-irradiated phage: Multi-hit kinetics of mutation induction and lack of indirect induction by infection with UV-irradiated phage of error-prone repair

International Nuclear Information System (INIS)

Krauss, G.; Mennigmann, H.D.; Kaplan, R.W.

1980-01-01

The paper is concerned with the question of whether Weigle-reactivation (WR) and Weigle-mutagenesis (WM) can be indirectly induced by infection with UV-irradiated phage. Experiments neither with phage lambda of Escherichia coli nor with phage kappa of Serratia marcescens show such induction. In this respect phage DNA differs from F'-DNA or Hfr-DNA; possible explanations are discussed. In both systems clear plaque mutations can also be induced by UV without irradiation of the host cells; they appear, in unirradiated and irradiated host cells, with an increase in frequency which is greater than proportional to the UV dose. It is concluded that mutation induction of phage in the unirradiated host cells is due to a low level constitutive mutagenic repair; this could either be due to 'spontaneous' induction of the mutagenic SOS function or it could be a mechanism different from this one. Host irradiation would give rise to additional activity by the induced SOS function leading to WR and WM. It is further concluded that deviation of the induction kinetics from a linear dose-dependence is not due to the necessary induction of SOS functions. (author)

[Study of gene mutation and pathogenetic mechanism for a family with Waardenburg syndrome].

Science.gov (United States)

Chen, Hongsheng; Liao, Xinbin; Liu, Yalan; He, Chufeng; Zhang, Hua; Jiang, Lu; Feng, Yong; Mei, Lingyun

2017-08-10

To explore the pathogenetic mechanism of a family affected with Waardenburg syndrome. Clinical data of the family was collected. Potential mutation of the MITF, SOX10 and SNAI2 genes were screened. Plasmids for wild type (WT) and mutant MITF proteins were constructed to determine their exogenous expression and subcellular distribution by Western blotting and immunofluorescence assay, respectively. A heterozygous c.763C>T (p.R255X) mutation was detected in exon 8 of the MITF gene in the proband and all other patients from the family. No pathological mutation of the SOX10 and SNAI2 genes was detected. The DNA sequences of plasmids of MITF wild and mutant MITF R255X were confirmed. Both proteins were detected with the expected size. WT MITF protein only localized in the nucleus, whereas R255X protein showed aberrant localization in the nucleus as well as the cytoplasm. The c.763C>T mutation of the MITF gene probably underlies the disease in this family. The mutation can affect the subcellular distribution of MITF proteins in vitro, which may shed light on the molecular mechanism of Waardenburg syndrome caused by mutations of the MITF gene.

Mutational spectrum analysis of umuC-independent and umuC-dependent γ-radiation mutagenesis in Escherichia coli

International Nuclear Information System (INIS)

Sargentini, N.J.; Smith, K.C.

1989-01-01

γ-radiation mutagenesis Escherichia coli K-12. Mutagenesis (argE3(OC) A rg + ) was blocked in a δ(recA-srlR)306 strain at the same doses that induced mutations in umuC122::Tn5 and wild-type strains, indicating that both umuC-independent and umuC-dependent mechanisms function within recA-dependent misrepair. Analyses of various suppressor and back mutations that result in argE3 and hisG4 ochre reversion and an analysis of trpE9777 reversion were performed on umuC and wild-type cells irradiated in the presence and absence of oxygen. While the umuC strain showed the γ-radiation induction of base substitution and frameshifts when irradiated in the absence of oxygen, the umuC mutation blocked all oxygen-dependent base-substitution mutagenesis, but non all oxygen-dependent frameshift mutagenesis. For anoxically irradiated cells, the yields of GC T and AT GC transitions were essentially umuC independent, while the yields of (AT or GC) TA transversions were heavily umuC dependent. These data suggest new concepts about the nature of the DNA lesions and the mutagenic mechanisms that lead to γ-radiation mutagenesis. (author). 48 refs.; 1 tab.; 6 refs

Mutation Breeding for Crop Improvement

International Nuclear Information System (INIS)

Rajbir, S. Sangwan

2017-01-01

Chromosomes contain genes responsible of different traits of any organism. Induced mutation using chemical mutagens and radiation to modify molecular structure of plants played a major role in the development of high genetic variability and help develop new superior crop varieties. The Mutation Breeding is applicable to all plants and has generated lot of agronomically interesting mutants, both in vegetatively and seed propagated plants. The technique is easy but long and challenging to detect, isolate and characterize the mutant and gene. A specific dose of irradiation has to be used to obtain desired mutants. However, with modern molecular technique, the gene responsible for mutation can be identified. The CRISPR-Cas9 allows the removal of a specific gene which is responsible of unwanted trait and replacing it with a gene which induces a desired trait. There have been more than 2700 officially released mutant varieties from 170 different plant species in more than 60 countries throughout the world and A more participatory approach, involving all stakeholders in plant breeding, is needed to ensure that it is demand/farmers driven.

Hyperthermia-induced alteration of yeast susceptibility to mutation

International Nuclear Information System (INIS)

Mitchel, R.E.J.; Morrison, D.P.

1985-01-01

Diploid yeast (s. cerevisiae) were examined for alterations in susceptibility to induced mutation following hyperthermia treatment. In cells grown at 23 0 C, a non-lethal heat exposure (38 0 C, 30 min) markedly suppressed mutation induced by a subsequent non-killing dose of MNNG of MNU. Mutation by ENU, 8-MOP + UVA, or γ-rays was not affected. An intermediate level of mutation suppression was observed for mutation by 254nm UV or MMS. Mutation by MNNG was not suppressed by the same heat treatment delivered after the mutagen exposure. In a split dose experiment (two MNNG treatments separated by a heat exposure) no suppression of mutation was observed. Treatment with cycloheximide mimicked the effect of heat treatment. These data suggest that mutation induction by MNNG or MNU is protein synthesis dependent, i.e. an error-prone repair system is induced by exposure to MNNG or MNU but not by ENU, 8-MOP+UVA or γ-irradiation. We propose that hyperthermia treatment, by inducing stress protein synthesis at the expense of normal protein synthesis, precludes induction of this error-prone system. Therefore, in heat treated cells, DNA lesions produced by MNNG or MNU exposure must be resolved by an essentially constitutive system which is less error-prone than the inducible one

Analysis of mutant frequencies and mutation spectra in hMTH1 knockdown TK6 cells exposed to UV radiation

Energy Technology Data Exchange (ETDEWEB)

Fotouhi, Asal [Center for Radiation Protection Research, Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University (Sweden); Hagos, Winta Woldai [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Ilic, Marina; Wojcik, Andrzej; Harms-Ringdahl, Mats [Center for Radiation Protection Research, Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University (Sweden); Gruijl, Frank de [Department of Dermatology, Leiden University Medical Center, Leiden (Netherlands); Mullenders, Leon; Jansen, Jacob G. [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Haghdoost, Siamak, E-mail: Siamak.Haghdoost@su.se [Center for Radiation Protection Research, Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University (Sweden)

2013-11-15

Highlights: • hMTH1 protects cells from mutagenesis induced by UVA and UVB, but not UVC. • No protective role of hMTH1 in cell survival post UVB and UVC irradiation. • hMTH1 prevents induction of transition-type mutations at AT and GC post UVA irradiation. • 2-OH-dATP rather than 8-oxo-dGTP in the nucleotide pool likely contributes in UVA-induced mutations. - Abstract: Ultraviolet radiation is a highly mutagenic agent that damages the DNA by the formation of mutagenic photoproducts at dipyrimidine sites and by oxidative DNA damages via reactive oxygen species (ROS). ROS can also give rise to mutations via oxidation of dNTPs in the nucleotide pool, e.g. 8-oxo-dGTP and 2-OH-dATP and subsequent incorporation during DNA replication. Here we show that expression of human MutT homolog 1 (hMTH1) which sanitizes the nucleotide pool by dephosphorylating oxidized dNTPs, protects against mutagenesis induced by long wave UVA light and by UVB light but not by short wave UVC light. Mutational spectra analyses of UVA-induced mutations at the endogenous Thymidine kinase gene in human lymphoblastoid cells revealed that hMTH1 mainly protects cells from transitions at GC and AT base pairs.

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).

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

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...

Biological effects of radiation and chemical agents with special regard to repair processes

International Nuclear Information System (INIS)

Altmann, H.; Wottawa, A.

1980-01-01

It is reasonably certain that the introduction or increase of pollutants in the environment can augment mutagenic and carcinogenic effects. These effects are operationally definable, but the genetic organization and the underlying mechanisms of DNA repair, mutagenesis and carcinogenesis are so complex as to make the extrapolation of results from mutagenicity test data to carcinogenicity somewhat uncertain. The subject is reviewed. Recent discoveries in gene organization and expression include overlapping genes in bacteriophages, split genes, processing of RNA and splicing, translocation of genes in eukaryotes, inactivation of the X-chromosome in mammals, etc. Apart from the genetic regulation, plasmids, insertion sequences and mutators can additionally affect mutation frequency. Cancers due to gene mutations, viruses, chemicals and physical agents are known. However, little is known about the epigenetic mechanisms involved. The value of mutagenicity test data is beyond question, but in view of the extraordinary complexities encountered our extrapolations will be more sound if the data have the underpinning of basic information. (author)

Utilization of Mutagenic Treatments for Improving Barley Disease Resistance to Powdery Mildew

International Nuclear Information System (INIS)

Amer, M.; Fahim, M.M.; Moustafa, N.A.

2008-01-01

This program aims to improve barley (Hordeum vulgar L.) resistance to powdery mildew (Erysiphe graminis f. sp. hordi) using mutation induction technique via physical and chemical mutagens. Grains of two local cultivars were treated with gamma rays (150, 250 GY) at a dose rate of 9.02 Rad/ Sec alone or with the concentrations of chemical mutagens, i.e.,EMS (4 and 8 mM), MH (10 and 20 mM) for two hours. After mass selection for the resistance in M2, the two cultivars were varied in their responses to the fifteen treatments. In M3 generation, the frequencies of plant resistance were increased at 20 mM of MH, 8 mM of EMS or 250 GY with either of them for the cultivar G124. However, the same trend was also found at 10 mM of MH, 250GY alone and with 4 or 8 mM EMS for cultivar G125. Moreover, eight mutants were selected from the progenies of M4 plants and evaluated in M5 generation. These mutants are characterized by highly disease resistance and high yield components, one of them has been characterized by non crytics and awnless .The desirable mutants should go to further evaluation for grain yield and grain quality in subsequent generations. (author)

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.

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

The Mutagenic Potential Caused by the Emissions from Combustion of Crude Glycerin and Diesel Fuel

Directory of Open Access Journals (Sweden)

Daniel Terruggi Mazak

2015-04-01

Full Text Available This study evaluated the use of crude glycerin as an alternative of energy generation to replace the traditional fuels. The Tradescantia stamen hair mutation assay (Trad-SH was applied to study the mutagenic effects caused by the emissions generated in the direct combustion of diesel oil and glycerin in a flame tube furnace. Tradescantia inflorescences were exposed to gaseous emissions from the combustion tests in a fumigation chamber for 30-40 min. The analysis of variance and the Tukey test were applied to compare the differences between six test groups (intoxicated with emissions from glycerin and diesel oil combustion and a control group. Only one glycerin group showed statistical differences (0.05, possibly due to the complexity of the burning process and impurities, besides the acrolein present in its emissions. The high heating value (HHV of crude glycerin (25.5 MJ/kg was lower than diesel oil (45.19 MJ/kg, but it was comparable to other fuels. Although the use of glycerin as a biofuel could be an important aspect to be considered, the results showed that the glycerin had a substantial mutagenic potential similar to that of diesel oil.

Utilization of radiations in mutation breeding of tuber crops

International Nuclear Information System (INIS)

Kukimura, H.

1981-01-01

Most of the tuber crops are vegetatively propagated and their spontaneous mutations have been constructively utilized to practical farming. Significance of utilization of mutations to breeding should not be overlooked, since mutation can be articially induced by various mutagenic agents. In tuber crops, ionizing radiations are mostly applied to induce mutations. Radiosensitivity varies with species, genotypes and organs. For the purpose of mutation induction, 10-20 kR of gamma-rays is given to tubers and/or shoots in sweet potato and 2-10 kR in potato. It should be noted that radiation damage is more or less transmissible to later vegetative generations. A useful characters in practical agriculture, following mutations have been obtained so far: skin colour, short stemmed, changes in dry matter content, total sugars content and tuber yield, earlier maturity and sculf resistance in sweet potato. And, skin colour, changes in starch content and stolon length, day-neutral tuberization and cyst-nematode resistance in potato. Apart from mutations, radiation can be utilized for breaking down the incompatibility in sweet potato. Promising mutant clones with probable release in Japan are Kyushu 78 of sweet potato and Koniku 16 and Konkei 55 of potato. (author)

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.

Environmental modulation of somatic mutations: nature of interactions. Final report, 1 June 1974--31 May 1977

International Nuclear Information System (INIS)

Mericle, L.W.

1977-05-01

Research on this project has had as a major goal a combined ecologic-genetic investigation of somatic mutations in order to evaluate the impacts of certain changing environmental parameters. The ultimate aim, to better understand how such environmental-mutation interactions operate and to assure the information obtained be extrapolatable to conditions and events in nature. Higher plants delineate reproductive tissues late in development from meristematic, somatic tissues. Moreover, the prevailing method of reproduction may be without sexual fusion of gametes and/or wholly asexual (vegetative). Therefore, somatic mutations can have as far-reaching genetic significance for a plant population as when germ cells, themselves, are directly affected. Our data show diurnal temperature differences (DTD) of greater than or equal to 22.2 C-degrees to be very effective mutagenic agents in the Tradescantia somatic mutation system. Further, these ranges of DTD were found to occur often in important seed production areas. A DTD of 22.2 in magnitude can increase mutations 10-fold. And, durations short as 1-day can induce significant increases in mutation rate. Whether interaction of 22.2 DTD with low-level radiation (800 mR/day) is synergistic or attenuative is still debatable. We believe, however, that spontaneous, and 22.2 DTD induced, mutations occur mainly via the genetic mechanism of somatic crossing-over; mutations from acute ionizing radiation (e.g., 30-60 R γ) via chromosome breakage, producing micronuclei. Requirements for maximizing the Discriminatory Response Capability (DRC) in the Tradescantia somatic mutation system are set forth

Studies on elemental analysis of Chinese traditional herbs by neutron activation technique and their mutagenic effect

International Nuclear Information System (INIS)

Hamzah, A.; Beh, C.W.; Abugassa, I.; Sarmani, S.B.; Liow, J.Y.

2004-01-01

Chinese herbs are accepted as an alternative medicine for specific treatment of illness. It is important to know the contents of these herbs that might cause gene mutation. Ten most popular herbs used in Malaysia were analyzed by instrumental neutron activation analysis. A total of 16 trace and major elements were determined and the concentration of elements varied depending on the origin of the herb. Toxic elements found in the samples were below the levels prescribed by health regulations. The mutagenicity test showed that there was no toxic effect due to the heavy metals present in the herbs. (author)

Non-homologous end joining dependency of {gamma}-irradiation-induced adaptive frameshift mutation formation in cell cycle-arrested yeast cells

Energy Technology Data Exchange (ETDEWEB)

Heidenreich, Erich [Institute of Cancer Research, Division of Molecular Genetics, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria)]. E-mail: erich.heidenreich@meduniwien.ac.at; Eisler, Herfried [Institute of Cancer Research, Division of Molecular Genetics, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria)

2004-11-22

There is a strong selective pressure favoring adaptive mutations which relieve proliferation-limiting adverse living conditions. Due to their importance for evolution and pathogenesis, we are interested in the mechanisms responsible for the formation of such adaptive, gain-of-fitness mutations in stationary-phase cells. During previous studies on the occurrence of spontaneous reversions of an auxotrophy-causing frameshift allele in the yeast Saccharomyces cerevisiae, we noticed that about 50% of the adaptive reversions depended on a functional non-homologous end joining (NHEJ) pathway of DNA double-strand break (DSB) repair. Here, we show that the occasional NHEJ component Pol4, which is the yeast ortholog of mammalian DNA polymerase lambda, is not required for adaptive mutagenesis. An artificially imposed excess of DSBs by {gamma}-irradiation resulted in a dramatic increase in the incidence of adaptive, cell cycle arrest-releasing frameshift reversions. By the use of DNA ligase IV-deficient strains we detected that the majority of the {gamma}-induced adaptive mutations were also dependent on a functional NHEJ pathway. This suggests that the same mutagenic NHEJ mechanism acts on spontaneously arising as well as on ionizing radiation-induced DSBs. Inaccuracy of the NHEJ repair pathway may extensively contribute to the incidence of frameshift mutations in resting (non-dividing) eukaryotic cells, and thus act as a driving force in tumor development.

Non-homologous end joining dependency of γ-irradiation-induced adaptive frameshift mutation formation in cell cycle-arrested yeast cells

International Nuclear Information System (INIS)

Heidenreich, Erich; Eisler, Herfried

2004-01-01

There is a strong selective pressure favoring adaptive mutations which relieve proliferation-limiting adverse living conditions. Due to their importance for evolution and pathogenesis, we are interested in the mechanisms responsible for the formation of such adaptive, gain-of-fitness mutations in stationary-phase cells. During previous studies on the occurrence of spontaneous reversions of an auxotrophy-causing frameshift allele in the yeast Saccharomyces cerevisiae, we noticed that about 50% of the adaptive reversions depended on a functional non-homologous end joining (NHEJ) pathway of DNA double-strand break (DSB) repair. Here, we show that the occasional NHEJ component Pol4, which is the yeast ortholog of mammalian DNA polymerase lambda, is not required for adaptive mutagenesis. An artificially imposed excess of DSBs by γ-irradiation resulted in a dramatic increase in the incidence of adaptive, cell cycle arrest-releasing frameshift reversions. By the use of DNA ligase IV-deficient strains we detected that the majority of the γ-induced adaptive mutations were also dependent on a functional NHEJ pathway. This suggests that the same mutagenic NHEJ mechanism acts on spontaneously arising as well as on ionizing radiation-induced DSBs. Inaccuracy of the NHEJ repair pathway may extensively contribute to the incidence of frameshift mutations in resting (non-dividing) eukaryotic cells, and thus act as a driving force in tumor development

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.

Mutation induction in Lathyrus sativus L

International Nuclear Information System (INIS)

Singh, M.; Chaturvedi, S.N.

1989-01-01

Full text: Seeds of the grass pea varieties 'LSD 6' and 'S 220' were treated with 10-25 kR gamma rays, 0.1-0.4% EMS or 0.01-0.04% NMH. DMSO in 1% solution applied together with 10 kR gamma rays, 0.1% EMS or 0.01% NMH increased the effects of the mutagens. M 2 progenies were checked for morphological and leaf color mutations. From data obtained the following treatments appear appropriate: 15kR gamma rays; 10 kR gamma rays + DMSO; 0.1% EMS; 0.01% NMH. (author)

Diploid yeast cells yield homozygous spontaneous mutations

Science.gov (United States)

Esposito, M. S.; Bruschi, C. V.; Brushi, C. V. (Principal Investigator)

1993-01-01

A leucine-requiring hybrid of Saccharomyces cerevisiae, homoallelic at the LEU1 locus (leu1-12/leu1-12) and heterozygous for three chromosome-VII genetic markers distal to the LEU1 locus, was employed to inquire: (1) whether spontaneous gene mutation and mitotic segregation of heterozygous markers occur in positive nonrandom association and (2) whether homozygous LEU1/LEU1 mutant diploids are generated. The results demonstrate that gene mutation of leu1-12 to LEU1 and mitotic segregation of heterozygous chromosome-VII markers occur in strong positive nonrandom association, suggesting that the stimulatory DNA lesion is both mutagenic and recombinogenic. In addition, genetic analysis of diploid Leu+ revertants revealed that approximately 3% of mutations of leu1-12 to LEU1 result in LEU1/LEU1 homozygotes. Red-white sectored Leu+ colonies exhibit genotypes that implicate post-replicational chromatid breakage and exchange near the site of leu1-12 reversion, chromosome loss, and subsequent restitution of diploidy, in the sequence of events leading to mutational homozygosis. By analogy, diploid cell populations can yield variants homozygous for novel recessive gene mutations at biologically significant rates. Mutational homozygosis may be relevant to both carcinogenesis and the evolution of asexual diploid organisms.

Charged-particle mutagenesis 2. Mutagenic effects of high energy charged particles in normal human fibroblasts

Science.gov (United States)

Chen, D. J.; Tsuboi, K.; Nguyen, T.; Yang, T. C.

1994-01-01

The biological effects of high Linear Energy Transfer (LET) charged particles are a subject of great concern with regard to the prediction of radiation risk in space. In this report, mutagenic effects of high LET charged particles are quantitatively measured using primary cultures of human skin fibroblasts, and the spectrum of induced mutations are analyzed. The LET of the charged particles ranged from 25 KeV/micrometer to 975 KeV/micrometer with particle energy (on the cells) between 94-603 MeV/u. The X-chromosome linked hypoxanthine guanine phosphoribosyl transferase (hprt) locus was used as the target gene. Exposure to these high LET charged particles resulted in exponential survival curves; whereas, mutation induction was fitted by a linear model. The Relative Biological Effect (RBE) for cell-killing ranged from 3.73 to 1.25, while that for mutant induction ranged from 5.74 to 0.48. Maximum RBE values were obtained at the LET of 150 keV/micrometer. The inactivation cross-section (alpha i) and the action cross-section for mutant induction (alpha m) ranged from 2.2 to 92.0 sq micrometer and 0.09 to 5.56 x 10(exp -3) sq micrometer respectively. The maximum values were obtained by Fe-56 with an LET of 200 keV/micrometer. The mutagenicity (alpha m/alpha i) ranged from 2.05 to 7.99 x 10(exp -5) with the maximum value at 150 keV/micrometer. Furthermore, molecular analysis of mutants induced by charged particles indicates that higher LET beams are more likely to cause larger deletions in the hprt locus.

Studies on mutagenic effectiveness and efficiency of gamma rays and its effect on quantitative traits in finger millet (Eleusine coracana L. Gaertn

Directory of Open Access Journals (Sweden)

A.R. Ambavane

2015-01-01

Full Text Available Dry seeds (12% moisture of two finger millet cultivar viz., Dapoli-1 and Dapoli Safed were irradiated with four doses of gamma-rays viz., 400 Gy, 500 Gy, 600 Gy and 700 Gy at BARC, Mumbai. In laboratory test, root and shoot lengths of seedlings were decreased with increase in dose of gamma rays. Similarly, germination percentage and survival rate of seedlings were decreased with increase in dose of gamma irradiation during field study. In M1 generation, three types of chlorophyll mutations viz., albino, xantha and viridis were observed. Albino and xantha were observed in all treatments, whereas, viridis observed only in lower doses viz., 400 Gy and 500 Gy. Based on the chlorophyll mutation frequency on M1 plants, mutagenic effectiveness and efficiency were computed. In Dapoli-1 variety, two early maturing mutants and three high yielding mutants were isolated from 500 Gy dose and 600 Gy dose, respectively. In M2 generation, the mutagenic treatments were effective in inducing various types of chlorophyll and morphological macro mutants, few of those show significant change in flowering, maturity and plant height character and few of them have good breeding value.

Preclinical test: bacterial reverse mutation test for 18F-fluorocholine produced in CDTN

International Nuclear Information System (INIS)

Mendes, Bruno M.; Bispo, Ana Carolina A.; Campos, Danielle C.; Silva, Juliana B.

2013-01-01

The choline labeled with fluorine-18 (18FCH) is being considered as a great importance radiopharmaceutical due to its effective detection of many type of malignant neoplasm. The research related to 18 F-fluorocholine synthesis in CDTN was initiated in 2010. In order to obtain clinical research approval, as well as to register 18 FCH for marketing, safety and efficacy preclinical testing are required. The present work evaluated the 18 FCH genotoxic potential through the bacterial reverse mutation test (Ames test) using Salmonella typhimurium TA-98, TA-100, TA-1535 and TA-1537 strains and Escherichia coli WP2 uvrA strain. The reverse mutation test in bacteria for fluorcolina was conducted in two stages. Initially the method was applied to 'cold' fluorocholine molecule (19FCH). Subsequently, the decayed product of 18 FCH synthesis was evaluated. The first step was performed in order to examine the FCH molecule mutagenicity. The second was carried out to determine the mutagenic potential of final product. All strains were tested in triplicate for each exposure concentration, in the presence and absence of metabolic activation (S-9 mix - 10%). There were no statistically significant increases in revertant colonies rate for any strains tested after their exposure to decayed 18 FCH or 19 FCH. The number of revertant colonies in positive controls was significantly higher than that observed in significant increases in revertant colonies rate for any strains tested after their exposure to decayed 18 FCH or 19 FCH. The number of revertant colonies in positive controls was significantly higher than that observed in negative controls. Based on results of this assay, 18 FCH and 19 FCH, at tested doses, were found to be non-mutagenic in bacterial reverse mutation test. (author)

Induced mutagenesis as a source of new mutations in maize (Zea mays L.)

Energy Technology Data Exchange (ETDEWEB)

Mashnenkov, A S [Krasnodar Research Institute of Agriculture, Krasnodar (USSR)

1990-01-01

Full text: Seed samples of 9 inbreds were treated with MNU. Mutant individuals were visually selected in M{sub 2} and M{sub 3}. Mutability was determined in 100 loci by crossing induced mutants with some well-known natural mutants obtained from the U.S. Association of Corn Geneticists. Only viable mutants characterised with distinct stable traits connected with kernel texture and mature plant were taken for tests. Mapping of the expected new mutants was realised through A-B translocations and marker lines. Evaluation of the mutant alleles' effect on yield and quality of biomass in inbreds and heterotic hybrids was done by the standard methods. The results show the ability of artificial mutagens to induce mutations in previously known loci. The genotype of the inbreds greatly affects the probability of mutation occurrence in a new locus. Due to the mutagen effect, independently inherited complexes of traits or naturally polygenic traits may become monogenic. This results in simplified inheritance, in an increase in heritability and thus in high effectiveness of selection. (author)

Induced mutagenesis as a source of new mutations in maize (Zea mays L.)

International Nuclear Information System (INIS)

Mashnenkov, A.S.

1990-01-01

Full text: Seed samples of 9 inbreds were treated with MNU. Mutant individuals were visually selected in M 2 and M 3 . Mutability was determined in 100 loci by crossing induced mutants with some well-known natural mutants obtained from the U.S. Association of Corn Geneticists. Only viable mutants characterised with distinct stable traits connected with kernel texture and mature plant were taken for tests. Mapping of the expected new mutants was realised through A-B translocations and marker lines. Evaluation of the mutant alleles' effect on yield and quality of biomass in inbreds and heterotic hybrids was done by the standard methods. The results show the ability of artificial mutagens to induce mutations in previously known loci. The genotype of the inbreds greatly affects the probability of mutation occurrence in a new locus. Due to the mutagen effect, independently inherited complexes of traits or naturally polygenic traits may become monogenic. This results in simplified inheritance, in an increase in heritability and thus in high effectiveness of selection. (author)

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.

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...

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.

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.

Two-dimensional IR spectroscopy of the anti-HIV agent KP1212 reveals protonated and neutral tautomers that influence pH-dependent mutagenicity

OpenAIRE

Peng, Chunte Sam; Fedeles, Bogdan I.; Singh, Vipender; Li, Deyu; Amariuta, Tiffany; Essigmann, John M.; Tokmakoff, Andrei

2015-01-01

The anti-HIV drug KP1212 was designed to intentionally increase the mutation rate of HIV, thereby causing viral population collapse. Its mutagenicity and thus antiviral activity was proposed to be the result of tautomerization. We used 2D IR spectroscopy to identify rapidly interconverting tautomers under physiological conditions. The traditionally rare enol–imino tautomer for nucleobases was found to be the major species for KP1212, providing a structural support for the tautomer hypothesis....

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

Mutagenic adaptive response to high-LET radiation in human lymphoblastoid cells exposed to X-rays.

Science.gov (United States)

Varès, Guillaume; Wang, Bing; Tanaka, Kaoru; Kakimoto, Ayana; Eguchi-Kasai, Kyomi; Nenoi, Mitsuru

2011-01-10

The ability of cells to adapt low-dose or low-dose rate radiation is well known. High-LET radiation has unique characteristics, and the data concerning low doses effects and high-LET radiation remain fragmented. In this study, we assessed in vitro the ability of low doses of X-rays to induce an adaptive response (AR) to a subsequent challenging dose of heavy-ion radiation. Lymphoblastoid cells (TK6, AHH-1, NH32) were exposed to priming 0.02-0.1Gy X-rays, followed 6h later by challenging 1Gy heavy-ion radiation (carbon-ion: 20 and 40keV/μm, neon-ion: 150keV/μm). Pre-exposure of p53-competent cells resulted in decreased mutation frequencies at hypoxanthine-guanine phosphoribosyl transferase locus and different H2AX phosphorylation kinetics, as compared to cells exposed to challenging radiation alone. This phenomenon did not seem to be linked with cell cycle effects or radiation-induced apoptosis. Taken together, our results suggested the existence of an AR to mutagenic effects of heavy-ion radiation in lymphoblastoid cells and the involvement of double-strand break repair mechanisms. Copyright © 2010 Elsevier B.V. All rights reserved.

Evaluation of acute and subacute toxicity and mutagenic activity of the aqueous extract of pecan shells [Carya illinoinensis (Wangenh.) K. Koch].

Science.gov (United States)

Porto, Luiz Carlos Santos; da Silva, Juliana; Ferraz, Alexandre de Barros Falcão; Corrêa, Dione Silva; dos Santos, Marcela Silva; Porto, Caroline Dalla Lana; Picada, Jaqueline Nascimento

2013-09-01

The infusion of pecan shells has been used to prevent and control hypercholesterolemia, diabetes and toxicological diseases. The aim of the present study was to evaluate toxicity and mutagenic effects of pecan shells aqueous extract (PSAE). Wistar rats were treated with a single dose of 300 or 2000 mg/kg of PSAE in the acute toxicity test. For the subacute test, the animals received 10 or 100 mg/kg of PSAE for 28 days. The mutagenicity was evaluated using Salmonella/microsome assay in TA1535, TA1537, TA98, TA100 and TA102 S. typhimurium strains in the presence and absence of metabolic activation (S9 mix) and micronucleus test in bone marrow. HPLC analyses indicated the presence of tannins, flavonoids, gallic and ellagic acids. Except for triglycerides, all treated groups presented normal hematological and biochemical parameters. Lower levels of triglycerides and weight loss were observed in the 100 mg/kg group. Mutagenic activities were not detected in S. typhimurium strains and by the micronucleus test. Based on these results, PSAE was not able to induce chromosomal or point mutations, under the conditions tested. The 100mg/kg dose showed significant antihyperlipidemic action, with no severe toxic effects. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ion Torrent sequencing as a tool for mutation discovery in the flax (Linum usitatissimum L.) genome.

Science.gov (United States)

Galindo-González, Leonardo; Pinzón-Latorre, David; Bergen, Erik A; Jensen, Dustin C; Deyholos, Michael K

2015-01-01

Detection of induced mutations is valuable for inferring gene function and for developing novel germplasm for crop improvement. Many reverse genetics approaches have been developed to identify mutations in genes of interest within a mutagenized population, including some approaches that rely on next-generation sequencing (e.g. exome capture, whole genome resequencing). As an alternative to these genome or exome-scale methods, we sought to develop a scalable and efficient method for detection of induced mutations that could be applied to a small number of target genes, using Ion Torrent technology. We developed this method in flax (Linum usitatissimum), to demonstrate its utility in a crop species. We used an amplicon-based approach in which DNA samples from an ethyl methanesulfonate (EMS)-mutagenized population were pooled and used as template in PCR reactions to amplify a region of each gene of interest. Barcodes were incorporated during PCR, and the pooled amplicons were sequenced using an Ion Torrent PGM. A pilot experiment with known SNPs showed that they could be detected at a frequency > 0.3% within the pools. We then selected eight genes for which we wanted to discover novel mutations, and applied our approach to screen 768 individuals from the EMS population, using either the Ion 314 or Ion 316 chips. Out of 29 potential mutations identified after processing the NGS reads, 16 mutations were confirmed using Sanger sequencing. The methodology presented here demonstrates the utility of Ion Torrent technology in detecting mutation variants in specific genome regions for large populations of a species such as flax. The methodology could be scaled-up to test >100 genes using the higher capacity chips now available from Ion Torrent.

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

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)

Mutation induction by and mutational interaction between monochromatic wavelength radiations in the near-ultraviolet and visible ranges

International Nuclear Information System (INIS)

Tyrrell, R.M.

1980-01-01

The induction of mutations (reversion to tryptophan independence) by various UV (254, 313, 334 and 365 nm) and visible (405 and 434 nm) wavelengths was measured in exponential phase populations of Escherichia coli B/r thy trp and B/r thy trp uvr A by assay of irradiated populations on semi-enriched media. No mutations were induced in the repair proficient strain at wavelengths longer than 313 nm. Mutations were induced to the excisionless strain at wavelengths as long as 405 nm but less than expected from the known amount of DNA damage induced. Irradiation at the long wavelenths (434, 405, 365 and 334 nm) suppressed the appearance of 254- or 313 nm-induced mutations in the repair competent strain but not in the excision deficient strain. The relative dose-requirement for mutation suppression was related to the relative efficiency of these wavelengths in inducing growth delay. These results suggest that the growth delay induced by near-UV and visible wavelenghts allows more time for the 'error-free' excision repair process to act on the potentially mutagenic lesions induced by 254- and 313-nm radiations, thereby reducing the mutation frequency observed in the repair-proficient strain. The level of near-UV mutation induced in the excision deficient strain is lower than expected from the DNA damage known to be induced. It is possible that near-UV radiation induces a class of lethal lesions that are not susceptible to error-prone repair. (author)

A study on mutagenic effects of antibiotic-producers by ion implantation

International Nuclear Information System (INIS)

Xie Liqing; Zhang Yinfen; Chen Ruyi; Zhou Ruiying; Zhang Peiling; Ying Hengfeng; Yang Guorong; Yang Guifang

1995-01-01

Mutagenic effects of Streptomyces ribosidificus, Streptomyces kanamyceticus and the phage-resistant culture of Streptomyces kanamyceticus induced by N + and C + ion implantation with different doses have been investigated. The experimental results show that the death rates of antibiotic-producers increase with the increase of ion implantation dose, and the form mutation of the antibiotic-producers is rather obvious. After N + ion implantation, the titer units increase by 10%-25%, 5.2%-12.1% and 2.1%-12.75% for the above three strains respectively; while after C + ion implantation the titer units increase by 10%-16.9%, 1.05%-3.08% and 5%-20% respectively. The selected strains of Micromonospora echimospoora and Streptomyces kanamyceticus after N + ion implantation have been used in the factory. The increase of production is 20% and 12.5% respectively and marked economic benefits are obtained

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.