[Mutagenic evaluation of the urine of rats treated with oils implicated in the toxic oil syndrome using bacterial tests].

PubMed

Barrueco, C; Sladek, F; Canga, C; Valcarce, E; de la Peña, E; Alia, M; Laborda, E

1983-01-01

The mutagenic activity of the urine of pregnant rats treated with toxic oil syndrome-related rape seed oil or with edible oil was evaluated by means of the Ames and Green tests. It was found that the urine of the pregnant rats treated with "Jen" oil, that was related to the toxic oil syndrome, was mutagenic.

Development of fecal microbial enzyme mix for mutagenicity assay of natural products.

PubMed

Yeo, Hee Kyung; Hyun, Yang-Jin; Jang, Se-Eun; Han, Myung Joo; Lee, Yong Sup; Kim, Dong-Hyun

2012-06-01

Orally administered herbal glycosides are metabolized to their hydrophobic compounds by intestinal microflora in the intestine of animals and human, not liver enzymes, and absorbed from the intestine to the blood. Of these metabolites, some, such as quercetin and kaempherol, are mutagenic. The fecal bacterial enzyme fraction (fecalase) of human or animals has been used for measuring the mutagenicity of dietary glycosides. However, the fecalase activity between individuals is significantly different and its preparation is laborious and odious. Therefore, we developed a fecal microbial enzyme mix (FM) usable in the Ames test to remediate the fluctuated reaction system activating natural glycosides to mutagens. We selected, cultured, and mixed 4 bacteria highly producing glycosidase activities based on a cell-free extract of feces (fecalase) from 100 healthy Korean volunteers. When the mutagenicities of rutin and methanol extract of the flos of Sophora japonica L. (SFME), of which the major constituent is rutin, towards Salmonella typhimurium strains TA 98, 100, 102, 1,535, and 1,537 were tested using FM and/or S9 mix, these agents were potently mutagenic. These mutagenicities using FM were not significantly different compared with those using Korean fecalase. SFME and rutin were potently mutagenic in the test when these were treated with fecalase or FM in the presence of S9 mix, followed by those treated with S9 mix alone and those with fecalase or FM. Freeze-dried FM was more stable in storage than fecalase. Based on these findings, FM could be usable instead of human fecalase in the Ames test.

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

EPA Science Inventory

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

A novel QSAR model of Salmonella mutagenicity and its application in the safety assessment of drug impurities

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

Valencia, Antoni; Prous, Josep; Mora, Oscar

As indicated in ICH M7 draft guidance, in silico predictive tools including statistically-based QSARs and expert analysis may be used as a computational assessment for bacterial mutagenicity for the qualification of impurities in pharmaceuticals. To address this need, we developed and validated a QSAR model to predict Salmonella t. mutagenicity (Ames assay outcome) of pharmaceutical impurities using Prous Institute's Symmetry℠, a new in silico solution for drug discovery and toxicity screening, and the Mold2 molecular descriptor package (FDA/NCTR). Data was sourced from public benchmark databases with known Ames assay mutagenicity outcomes for 7300 chemicals (57% mutagens). Of these data, 90%more » was used to train the model and the remaining 10% was set aside as a holdout set for validation. The model's applicability to drug impurities was tested using a FDA/CDER database of 951 structures, of which 94% were found within the model's applicability domain. The predictive performance of the model is acceptable for supporting regulatory decision-making with 84 ± 1% sensitivity, 81 ± 1% specificity, 83 ± 1% concordance and 79 ± 1% negative predictivity based on internal cross-validation, while the holdout dataset yielded 83% sensitivity, 77% specificity, 80% concordance and 78% negative predictivity. Given the importance of having confidence in negative predictions, an additional external validation of the model was also carried out, using marketed drugs known to be Ames-negative, and obtained 98% coverage and 81% specificity. Additionally, Ames mutagenicity data from FDA/CFSAN was used to create another data set of 1535 chemicals for external validation of the model, yielding 98% coverage, 73% sensitivity, 86% specificity, 81% concordance and 84% negative predictivity. - Highlights: • A new in silico QSAR model to predict Ames mutagenicity is described. • The model is extensively validated with chemicals from the FDA and the public domain. • Validation

Seasonal and spatial variation of the bacterial mutagenicity of fine organic aerosol in southern california.

PubMed Central

Hannigan, M P; Cass, G R; Lafleur, A L; Busby, W F; Thilly, W G

1996-01-01

The bacterial mutagenicity of a set of 1993 urban particulate air pollution samples is examined using the Salmonella typhimurium TM677 forward mutation assay. Amibent fine particulate samples were collected for 24 hr every sixth day throughout 1993 at four urban sites, including Long Beach, central Los Angeles, Azusa, and Rubidoux, California, and at an upwind background site on San Nicolas Island. Long Beach and central Los Angeles are congested urban areas where air quality is dominated by fresh emissions from air pollution sources; Azuasa and Rubidoux are located farther downwind and receive transported air pollutants plus increased quantities of the products of atmospheric chemical reactions. Fine aerosol samples from Long Beach and Los Angeles show a pronounced seasonal variation in bacterial mutagenicity per cubic meter of- ambient air, with maximum in the winter and a minimum in the summer. The down-wind smog receptor site at Rubidoux shows peak mutagenicity (with postmitochondrial supernatant but no peak without postmitochondrial supernatant) during the September-October periods when direct transport from upwind sources can be expected. At most sites the mutagenicity per microgram of organic carbon from the aerosol is not obviously higher during the summer photochemical smog period than during the colder months. Significant spatial variation in bacterial mutagenicity is observed: mutagenicity per cubic meter of ambient air, on average, is more than an order of magnitude lower at San Nicolas Island than within the urban area. The highest mutagenicity values per microgram of organics supplied to the assay are found at the most congested urban sites at central Los Angeles and Long Beach. The highest annual average values of mutagenicity per cubic meter of air sampled occur at central Los Angeles. These findings stress the importance of proximity to sources of direct emissions of bacterial mutagens and imply that if important mutagen-forming atmospheric

Evaluation of a statistics-based Ames mutagenicity QSAR model and interpretation of the results obtained.

PubMed

Barber, Chris; Cayley, Alex; Hanser, Thierry; Harding, Alex; Heghes, Crina; Vessey, Jonathan D; Werner, Stephane; Weiner, Sandy K; Wichard, Joerg; Giddings, Amanda; Glowienke, Susanne; Parenty, Alexis; Brigo, Alessandro; Spirkl, Hans-Peter; Amberg, Alexander; Kemper, Ray; Greene, Nigel

2016-04-01

The relative wealth of bacterial mutagenicity data available in the public literature means that in silico quantitative/qualitative structure activity relationship (QSAR) systems can readily be built for this endpoint. A good means of evaluating the performance of such systems is to use private unpublished data sets, which generally represent a more distinct chemical space than publicly available test sets and, as a result, provide a greater challenge to the model. However, raw performance metrics should not be the only factor considered when judging this type of software since expert interpretation of the results obtained may allow for further improvements in predictivity. Enough information should be provided by a QSAR to allow the user to make general, scientifically-based arguments in order to assess and overrule predictions when necessary. With all this in mind, we sought to validate the performance of the statistics-based in vitro bacterial mutagenicity prediction system Sarah Nexus (version 1.1) against private test data sets supplied by nine different pharmaceutical companies. The results of these evaluations were then analysed in order to identify findings presented by the model which would be useful for the user to take into consideration when interpreting the results and making their final decision about the mutagenic potential of a given compound. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of mutagenic and antimutagenic activities of neem (Azadirachta indica) seed oil in the in vitro Ames Salmonella/microsome assay and in vivo mouse bone marrow micronucleus test.

PubMed

Vinod, V; Tiwari, P K; Meshram, G P

2011-04-12

The possible mutagenic and antimutagenic activity of neem oil (NO) and its DMSO extract (NDE) were, examined in the Ames Salmonella/microsome mutagenicity test and the mouse bone marrow micronucleus assay. Eight different strains of Salmonella typhimurium were, used to study the genotoxicity of neem oil both in the presence and absence of Aroclor-1254 induced rat liver homogenate (S9). Two-dose treatment protocol was, employed to study the cytogenetic activity in micronucleus assay. Similarly, the antimutagenic activity of neem oil and NDE was studied against mitomycin (MMC) and 7,12-dimethylbenz[a]anthracene (DMBA) in the above two test systems. Neem oil was non-mutagenic in all the eight tester strains of Salmonella typhimurium both in the presence and absence of S9 mix. In the present study, there was no significant increase in the frequency of micronucleated polychromatic erythrocytes (MNPCEs) in neem oil treated groups over the negative control (DMSO) group of animals, indicating the non-clastogenic activity of neem oil in the micronucleus test. Neem oil showed good antimutagenic activity against DMBA induced mutagenicity compared to its DMSO extract. However, neem oil showed comparatively less antimutagenicity against MMC in the Ames assay. In vivo anticlastogenic assays shows that neem oil exhibited better activity against DMBA induced clastogenicity. These results indicate non-mutagenic activity of neem oil and significant antimutagenic activity of neem oil suggesting its pharmacological importance for the prevention of cancer. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Di-epoxides of the three isomeric dicyclopenta-fused pyrenes: ultimate mutagenic active agents.

PubMed

Otero-Lobato, María José; Kaats-Richters, Veronica E M; Havenith, Remco W A; Jenneskens, Leonardus W; Seinen, Willem

2004-11-14

To rationalize the high bacterial mutagenic response recently found for the (di-) cyclopenta-fused pyrene congeners, viz. cyclopenta[cd]-(1), dicyclopenta[cd,mn]-(2), dicyclopenta[cd,fg]-(3) and dicyclopenta[cd,jk]pyrene (4), in the presence of a metabolic activation mixture (S9-mix), their (di-)epoxides at the externally fused unsaturated five-membered rings were previously proposed as the ultimate mutagenic active forms. In this study, cyclopenta[cd]pyrene-3,4-epoxide (5) and the novel dicyclopenta[cd,mn]pyrene-1,2,4,5-di-epoxide (6), dicyclopenta[cd,fg]pyrene-5,6,7,8-di-epoxide (7) and dicyclopenta[cd,jk]pyrene-1,2,6,7-di-epoxide (8) were synthesised from 1 to 4, respectively, and subsequently assayed for bacterial mutagenicity in the standard microsomal/histidine reverse mutation assay (Ames-assay with Salmonella typhimurium strain TA98). The di-epoxides 6-8 are present as a mixture of their cis- and trans-stereo-isomers in a close to 1:1 ratio ((1)H NMR spectroscopy and ab initio IGLO/III//RHF/6-31G** calculations). The direct-acting mutagenic activity and the strong cytotoxicity exerted by 5-8 both in the absence or presence of an exogenous metabolic activation system (+/-S9-mix) demonstrate that the ultimate mutagenic active forms are the proposed (di-)epoxides of 1-4.

Mutagenic Potential of p-Dithiane.

DTIC Science & Technology

1985-08-01

UNCLASSIFIED FGO 6/29 M 01. JLt * L, mia -l En.25 .4 166 MICROCOP RESOUTION TEST CHART an INSTITUTE REPORT NO. 207 LEC 10 MA20 I--- co DTI ( MUTAGENIC...mg/plate to 0.0016 mg/plate. The test compound was not mutagenic under conditions of this assay. Key Words: Mutagenicity, Genetic Toxicology, Ames...aliquot of the test compound will be retained in the LAIR Archives. TEST SUBSTANCE: p-Dithiane (TA039) INCLUSIVE STUDY DATES: 24 September - 12 October

Mutagenic screening of some commonly used medicinal plants in Nigeria.

PubMed

Akintonwa, Alade; Awodele, Olufunsho; Afolayan, Gbenga; Coker, Herbert A B

2009-09-25

The uses of medicinal plants have always been part of human culture. The World Health Organization estimates that up to 80% of the world's population relies on traditional medicinal system for some aspect of primary health care. However, there are few reports on the toxicological properties of most medicinal plants especially, their mutagenicity and carcinogenicity. Therefore, this research is to determine the mutagenic potentials of Morinda lucida [Oruwo (Root)], Azadirachta indica [Dongoyaro (Leaf)], Terapluera tetraptera [Aridan (Fruit)], Plumbago zeylanica [Inabiri (Root)], Xylopia aethiopica [Erunje (Fruit)], Newbouldia laevis [Akoko (Leaf)], Alstonia boonei [Ahun (Bark)], Enantia chlorantha [Awopa (Bark)], and Rauvolfia vomitoria [Asofeyeje (Root)] using the Allium cepa Linn. model and the modified Ames assay. Allium cepa model was used to determine the mean root length, mitotic index and chromosomal aberrations effects of these plants on onion bulbs using 0.1, 1, 5 and 10mg/ml concentration of the plant extracts. The modified Ames test which is a modification of the standard Ames test as described by Ames et al. [Ames, B.N., McCann, J., Yamasaki, E., 1975. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian microsome mutagenicity test. Mutation Research 31, 347-364] was done using Escherichia coli (0157:H7) that has the phenotypic characteristics of glucose and lactose fermentation, motile, urease negative, indole positive and citrate negative. The results obtained from Allium cepa assay showed increasing root growth inhibition with increased concentration, decreasing mitotic index with increased concentration and chromosomal aberrations. The modified Ames test showed an alteration in the biochemical characteristics of Escherichia coli (0157:H7) for all plants except Rauvolfia vomitoria and Plumbago zeylanica. Three of the medicinal plants altered at least three of the normal biochemical characteristics thus demonstrating mutagenic

Toxicologic characterization of a novel explosive, guanidinium 3,4-dinitropyrazolate (GDNP), in female rats and Ames mutagenicity assay.

PubMed

Williams, Larry R; Adams, Valerie H; Wallace, Shannon M; Johnson, Mark S

2012-01-01

Sustainable use of military training ranges requires the development of compounds that have a minimal impact to the environment when used in a weapon system. Guanidinium 3,4-dinitropyrazolate (GDNP) is a novel explosive compound of interest for application in some weapon systems. Little is known of its toxicologic properties. To ensure the health of potentially exposed personnel and the environment, initial toxicity investigations were conducted and the results were compared with another widely used energetic (hexahydro-1,3,5-trinitro-1,3,5-triazine [RDX]). In a microplate Ames assay, GDNP was not cytotoxic to bacterial tester strains at concentrations less than 100 μg/mL. However, GDNP was mutagenic to 4 of 5 bacterial strains with and without S9 metabolic incubation at concentrations as low as 0.7 μg/mL. Unlike RDX, GDNP did not have an affinity for the γ-aminobutyric acid(A) receptor convulsant site and was predicted to not induce seizure. After acute oral dosing in female rats, the median lethal dose in female rats of GDNP in tap water solution was determined to be 720 mg/kg. Daily oral exposure to 500 mg/kg per d of GDNP for 14 days caused weight loss, increased liver and spleen weights, and adverse histopathologic events in kidney and spleen. These adverse events were not observed in animals receiving lower doses of GDNP. In this study, the lowest-observed-adverse-effect-level from oral exposure to GDNP for 14 days was 500 mg/kg per d and the no-observable-adverse-effect-level was 152 mg/kg per d.

Cellular Mutagenicity and Heavy Metal Concentrations of Leachates Extracted from the Fly and Bottom Ash Derived from Municipal Solid Waste Incineration

PubMed Central

Chen, Po-Wen; Liu, Zhen-Shu; Wun, Min-Jie; Kuo, Tai-Chen

2016-01-01

Two incinerators in Taiwan have recently attempted to reuse the fly and bottom ash that they produce, but the mutagenicity of these types of ash has not yet been assessed. Therefore, we evaluated the mutagenicity of the ash with the Ames mutagenicity assay using the TA98, TA100, and TA1535 bacterial strains. We obtained three leachates from three leachants of varying pH values using the toxicity characteristic leaching procedure test recommended by the Taiwan Environmental Protection Agency (Taiwan EPA). We then performed the Ames assay on the harvested leachates. To evaluate the possible relationship between the presence of heavy metals and mutagenicity, the concentrations of five heavy metals (Cd, Cr, Cu, Pb, and Zn) in the leachates were also determined. The concentrations of Cd and Cr in the most acidic leachate from the precipitator fly ash and the Cd concentration in the most acidic leachate from the boiler fly ash exceeded the recommended limits. Notably, none of the nine leachates extracted from the boiler, precipitator, or bottom ashes displayed mutagenic activity. This data partially affirms the safety of the fly and bottom ash produced by certain incinerators. Therefore, the biotoxicity of leachates from recycled ash should be routinely monitored before reusing the ash. PMID:27827867

In vitro mutagenic, antimutagenic, and antioxidant activities evaluation and biotransformation of some bioactive 4-substituted 1-(2-methoxyphenyl)piperazine derivatives.

PubMed

Słoczyńska, Karolina; Pańczyk, Katarzyna; Waszkielewicz, Anna M; Marona, Henryk; Pękala, Elżbieta

2016-12-01

In vitro mutagenic, antimutagenic, and antioxidant potency evaluation and biotransformation of six novel 4-substituted 1-(2-methoxyphenyl)piperazine derivatives demonstrating antidepressant-like activity were investigated. Mutagenic and antimutagenic properties were assessed using the Ames test; free radical scavenging activity was evaluated with 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay and biotransformation was performed with liver microsomes. It was found that all tested compounds are not mutagenic in bacterial strains TA100 and TA1535 and exhibit antimutagenic effects in the Ames test. Noteworthy, compounds possessing propyl linker between phenoxyl and N-(2-methoxyphenyl)piperazine displayed more pronounced antimutagenic properties than derivatives with ethoxyethyl linker. Additionally, compounds 2 and 6 in vitro biotransformation showed that primarily their hydroxylated or O-dealkylated metabolites are formed. Some of the compounds exhibited intrinsic clearance values lower than those reported previously for antidepressant imipramine. To sum up, the results of the present study might represent a valuable step in designing and planning future studies with piperazine derivatives. © 2016 Wiley Periodicals, Inc.

Mutagenic activity of austocystins - secondary metabolites of Aspergillus ustus

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

Kfir, R.; Johannsen, E.; Vleggaar, R.

1986-11-01

Mycotoxins constitute a group of toxic secondary fungal metabolites. Fungi that produce these toxins frequently contaminate food and feed, creating a potential threat to human and animal health. Biological activities of mycotoxins include, amongst others: toxicity, mutagenicity and carcinogenicity, which can be expressed with or without metabolic activation. Austocystins are similar in structure to aflatoxin B/sup 1/ and are probably synthesized in a similar manner. The Ames Salmonella test, a widely accepted method employed for the detection of mutagenic activity of various chemical compounds was used for testing the mutagenic activity of different mycotoxins. As aflatoxin B/sup 1/ was foundmore » by the Ames test to be highly mutagenic, the same test was applied for the study of possible mutagenicity of the austocystins. The mutagenic activity of these compounds was studied with and without metabolic activation using two tester strains of S. typhimurium, one capable of detecting frame shift mutation (strain TA98) and the other capable of detecting base pair substitution (strain TA100).« less

2,3,7,8 tetrachlorodibenzodioxin in fish from the Pigeon river of Eastern Tennessee: Its toxicity and mutagenicity as revealed by the Ames Salmonella Assay

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

Blevins, R.D.

1990-04-01

Levels of 2,3,7,8 tetrachlorodibenzodioxin (TCDD)were determined in both striated muscle (fillets) and whole body extracts of fish specimens harvested during a two year period (1987-1989) from the Pigeon River (between Hartford and Newport) of Eastern Tennessee. Whole body (wet weight) fish extract levels as high as 117 {mu}g/kg body weight and composite fish fillet (wet weight) extract levels as high 87 {mu}g/kg fillet weight were observed. Pure TCDD was found to be highly toxic to the Salmonella typhimurium strains TA97, TA98, TA100, TA102 and TA1535 at TCDD dosages which exceeded 825 ng/ml in the top agar of the Ames Salmonellamore » assay. An 825 ng/ml TCDD dosage was not mutagenic to any of the tested Salmonella strains, (both with and without metabolic activation (S9) mix). However, when both acidic and alcohol fish extracts from the Pigeon River were tested for mutagenicity, several of the fish extracts were found to be mutagenic to Salmonella strains TA97, TA98, and TA100 (having mutagenic ratios which greatly exceeded the 2.5 {times} spontaneous ratio). These mutagenic extracts also demonstrated mutagenic dose-response curves. Other chemicals within the extracts as well as synergistic effects may account for the mutagenicity.« less

Mutagenic screening of diamine monomers

NASA Technical Reports Server (NTRS)

Ross, W. D.; Noble, J. E.; Gridley, J. A.; Fullenkamp, J. M.; Wininger, M. T.; Graham, J. A.

1983-01-01

The effects of phenyl ring coupling moieties, of isomeric amine positions relative to the coupling groups, and of insertion of other coupling groups on the mutagenic response of a series of dianilines were investigated using the Ames Salmonella assay. Generally, S-9 metabolic activation from Aroclor-induced rat liver was required for mutagenic expression. The range of mutagenicity of steric isomers of several dianiline series was also investigated. No mutagenicity was found for purified samples of o,o' and m,p' isomers of methylene dianiline (MDA) and diaminobenzophenone, while varying degrees of mutagenicity were found for other isomers. The mutagenicity of "benzylogs" of MDA decreased as the degree of linear separation of the m,m' anilino groups by aromatic rings increased. Methylation and two-year storage increased mutagenic response in certain isomers of MDA. However, high performance liquid chromatography indicated there was no discernible change in m,p'-MDA samples aged under varied conditions over four months. Likewise, no change in mutagenicity was found.

URINARY MUTAGENICITY: A BIOMARKER OF GENOTOXIC EXPOSURES VIA AIR, WATER, AND DIET

EPA Science Inventory

During the past 30 years, ~100 studies have evaluated human urine for mutagenic activity using the Salmonella (Ames) mutagenicity assay. Urinary mutagenicity has been shown to correlate well with other biomarkers, including DNA and hemoglobin adducts, urinary metabolites, and chr...

Assessment of the mutagenic potential of cyanobacterial extracts and pure cyanotoxins.

PubMed

Sieroslawska, Anna

2013-11-01

The aim of the study was to assess the mutagenic potential of extracts obtained from the cyanobacterial bloom-forming cells harvested from the water body located in Lubelszczyzna region of southeastern Poland. Three cyanotoxins, microcystin-LR, cylindrospermopsin and anatoxin-a were detected in some of the studied samples in different concentrations. All extracts were assessed for their potential mutagenic effects with the use of a short-term bacterial assay, the Ames test. Mutagenic activity was observed in four of all ten studied extracts, mainly toward the Salmonella typhimurium TA100 strain. On the contrary, the cyanotoxins in purified forms occurred not to be mutagenic or cytotoxic towards S. typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2 uvrA and WP2 [pKM101] up to a concentration of 10 μg/ml. Similarly, there were no effects after bacteria exposure to the mixture of purified toxins. It has been also detected that after fractionation, genotoxic impact of previously mutagenic extracts was weaker and the highest potency in revertant induction possessed fractions containing very hydrophilic compounds. The results indicate, that while tested cyanotoxins were not directly responsible for the observed mutagenicity of the extracts analysed, some synergistic interactions with other unidentified cyanobacterial-derived factors involved in the process are possible. Copyright © 2013 Elsevier Ltd. All rights reserved.

Characterization of mutagenic activity in grain-based coffee-substitute blends and instant coffees

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

Johansson, M.A.E.; Knize, M.G.; Felton, J.S.

1994-06-01

Several grain-based coffee-substitute blends and instant coffees showed a mutagenic response in the Ames/Salmonella test using TA98, YG1024 and YG1O29 with metabolic activation. The beverage powders contained 150 to 500 TA98 and 1150 to 4050 YG1024 revertant colonies/gram, respectively. The mutagenic activity in the beverage powders was shown to be stable to heat and the products varied in resistance to acid nitrite treatment. Characterization of the mutagenic activity, using HPLC-and the Ames test of the collected fractions, showed the coffee-substitutes and instant coffees contain several mutagenic compounds, which are most likely aromatic amines.

Mutagenic and clastogenic properties of 3-chloro-4-(dichloromethyl)-5-hydroxy-2 (5H)-furanone: a potent bacterial mutagen in drinking water

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

Meier, J.R.; Blazak, W.F.; Knohl, R.B.

1987-01-01

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) was found to be a direct-acting mutagen in the Ames test for strains TA1535, TA1538, TA92, TA97, TA98, TA100 and TA102. The highest mutagenic response (approximately 13,000 revertants/nmol) was seen in strain TA100. The TA100 response was six- to tenfold higher than in TA98, TA97, and TA102, and 100- to 500-fold higher than in TA1535, TA92, and TA1538. The addition of a 9,000 x g supernatant fraction (S-9) from livers of polychlorinated biphenyl-treated rats, along with cofactors for NADPH generation, resulted in a 90% reduction in the TA100 mutagenicity. MX induced chromosomal aberrations in Chinese hamster ovary cellsmore » after 6-8 hr exposure without S-9 at a dose as low as 4 micrograms/ml, and after 2 hr exposure with S-9 at a dose of 75 micrograms/ml. The oral dose of MX lethal to 50% (LD50) in Swiss-Webster mice was determined to be 128 mg/kg. MX did not induce micronuclei in mouse bone marrow when administered by oral gavage at doses up to 70% of the LD50.« less

Mutagenicity of benzotrichloride and related compounds.

PubMed

Yasuo, K; Fujimoto, S; Katoh, M; Kikuchi, Y; Kada, T

1978-11-01

Benzotrichloride (BTC), benzal chloride (BDC), benzyl chloride (BC) and benzoyl chloride (BOC) were surveyed for their mutagenicity in microbial systems such as rec-assay using Bacillus subtilis and reversion assays using E. coli WP2 and Ames Salmonella TA strains with or without metabolic activation in vitro. BTC and BDC required metabolic activation for their mutagenic activities in several strains of E. coli and Salmonella. The mutagenic metabolites of these compounds may not have been produced by hydrolysis. BC was weakly mutagenic without metabolic activation. Only BOC exhibited no mutagenic activity in the detection procedures used. The mutagenic metabolite of BTC might be very unstable under our experimental conditions. The strain E. coli WP2 try hcr was more sensitive than E. coli B/r WP2 try (hcr+) with regard to the mutagenicity of BTC.

A level change in mutagenicity of Japanese tap water over the past 12 yr.

PubMed

Takanashi, Hirokazu; Kishida, Misako; Nakajima, Tsunenori; Ohki, Akira; Akiba, Michihiro

2011-05-01

A relative comparison study of mutagenicity in Japanese tap water was conducted for 1993 and 2005 surveys. It intended to assess the effects of advanced water treatment installations to water works, improvement of raw water quality and improvement of residual HOCl concentration controlling. Sampling points (taps) were the same in both surveys. The results of 245 samples obtained by the Ames Salmonella mutagenicity test (Ames test) were analyzed. The Ames tests were conducted by using Salmonella typhimurium TA98 and TA100 strains with and without exogenous activation (S9). With the exception of TA100-S9, the other conditions needed no discussion as a factor in the mutagenicity level change. The average mutagenicity in 1993 and 2005 under the conditions of TA100-S9 were 2600 and 1100 net revertantL(-1), respectively. This indicated that the mutagenicity level of Japanese tap water decreased during the 12-yr period. Particularly a remarkable decrease in mutagenicity was observed in the water works where the advanced water treatments were installed during the 12-yr period. The advanced water treatments were effective in decreasing the mutagenicity of tap water. Mutagenicity also decreased in the water works with conventional water treatments; the improvement of residual HOCl concentration controlling was also considered to be effective in decreasing the mutagenicity of tap water. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cytotoxicity and mutagenicity of Kevlar: an in vitro evaluation.

PubMed

Wening, J V; Marquardt, H; Katzer, A; Jungbluth, K H; Marquardt, H

1995-03-01

Toxicity and mutagenicity of Kevlar 49 (PPPT; poly-para-phenylene-terephthalamide) was tested in six strains of Salmonella typhimurium (Ames test; TA97, TA98, TA100, TA102, TA1535, TA1537) with and without an external metabolic activation system (S9), as well as in a mammalian cell mutagenesis assay using V79 Chinese hamster cells. For the Ames test, liquid preincubation, which is considered particularly sensitive, was used. The cells were incubated for 24 h at a temperature of 37 degrees C either directly with Kevlar49 or with ethanol- or chloroform-extracted Kevlar49. The experiments were performed at least twice. The Ames test with six different Salmonella typhimurium strains featuring either base pair substitution or frameshift mutations revealed no cytotoxic or mutagenic activity of Kevlar49. In the mammalian cell mutagenesis assay, using 8-azaguanine (AG) as a selective agent, Kevlar49 was also devoid of cytotoxic or mutagenic activity. Both tests have to be regarded as an initial exploratory screening due to the chosen testing conditions and should be supplemented by tests at different temperatures.

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

EPA Science Inventory

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...

Hair dyes are mutagenic: identification of a variety of mutagenic ingredients.

PubMed Central

Ames, B N; Kammen, H O; Yamasaki, E

1975-01-01

We have previously described a sensitive bacterial test for dectecting carcinogens as mutagens. We have previously described a sensitive bacterial test for detecting carcinogens as mutagens. We show here that 89% (150/169) of commercial oxidative-type (hydrogen peroxide) hair dye formulations are mutagenic in this test. Of the 18 components of these hair dyes, nine show various degrees of mutagenicity:2,4-diaminoanisole, 4-nitro-o-phenylenediamine, 2-nitro-p-phenylenediamine, 2,5-diaminoanisole, 2-amino-5-nitrophenol, m-phenylenediamine, o-phenylenediamine, 2-amino-4-nitrophenol, and 2,5-diaminotoluene. Three hair dye components (p-phenylenediamine, 2,5-diaminotuluene, and 2,5-diaminoanisole) become strongly mutagenic after oxidation by H2O2: the mutagenic product of p-phenylenediamine is identified as the known trimer, Bandrowski's base. 2,4-Diaminotoluene, a hair dye component until recently, is also shown to be mutagenic: this compound has been shown to be a carcinogen in rats and is used in large amounts in the polyurethane foam industry. About 20,000,000 people (mostly women) dye their hair in the U.S. and the hazard could be considerable if these chemicals are actually mutagenic and carcinogenic in humans. Images PMID:1094469

Inhibitory effects of neem seed oil and its extract on various direct acting and activation-dependant mutagens-induced bacterial mutagenesis.

PubMed

Vijayan, Vinod; Tiwari, Pramod Kumar; Meshram, Ghansham Pundilikji

2013-12-01

Azadirachta indica A. Juss (Meliaceae), commonly called neem is a plant native to the Indian sub-continent. Neem oil extracted from the seeds of neem tree has shown promising medicinal properties. To investigate the possible anti-mutagenic activity of neem seed oil (NO) and its dimethylsulfoxide (DMSO) extract (NDE) on the mutagenicity induced by various direct acting and activation-dependant mutagens. The possible anti-mutagenic activity of NO (100-10,000 µg/plate) and NDE (0.1-1000 µg/plate) as well as the mechanism of anti-mutagenic activity was studied in an in vitro Ames Salmonella/microsome assay. NSO and NDE inhibited the mutagenic activity of methyl glyoxal (MG), in which case the extent of inhibition ranged from 65 to 77% and against 4-nitroquinoline-N-oxide (NQNO); it showed a 48-87% inhibition in the non-toxic doses. Similar response of NSO and NDE was seen against the activation-dependant mutagens aflatoxin B1 (AFB1, 48-88%), benzo(a)pyrene (B(a)P, 31-85%), cyclophosphamide (CP, 66-71%), 20-methylcholanthrane (20-MC, 37-83%) and acridine orange (AO, 39-72%) in the non-toxic doses. Mechanism-based studies indicated that NDE exhibits better anti-mutagenic activity in the pre- and simultaneous-treatment protocol against MG, suggesting that one or several active phytochemicals present in the extract covalently bind with the mutagen and prevent its interaction with the genome. These findings demonstrate that neem oil is capable of attenuating the mutagenic activity of various direct acting and activation-dependant mutagens.

Volatilization of mutagens from beef during cooking.

PubMed

Rappaport, S M; McCartney, M C; Wei, E T

1979-12-01

The process of cooking beef substances which are mutagenic in the Ames Salmonella/microsome bioassay [1,2]. In this study, the formation and disposition of basic mutagens produced by cooking beef at different temperatures were examined. Mutagenic activity increased exponentially with cooking temperature between 137 degrees C and 252 degrees C. However, the amount of mutagenic activity remaining in the meat was only 1--7% of that which was volatilized into the air. The ingested dose of mutagens may therefore be significantly influenced by factors which restrict the dissipation of mutagens from the container, as well as by cooking temperature. Inhalation of airborne mutagens from cooking, as an alternative route of exposure, should be investigated when considered in light of some epidemiological data showing an excess of lung and bladder cancer among cooks and kitchen workers.

The mutagenic assessment of an electronic-cigarette and reference cigarette smoke using the Ames assay in strains TA98 and TA100.

PubMed

Thorne, D; Crooks, I; Hollings, M; Seymour, A; Meredith, C; Gaca, M

2016-12-01

Salmonella typhimurium strains TA98 and TA100 were used to assess the mutagenic potential of the aerosol from a commercially available, rechargeable, closed system electronic-cigarette. Results obtained were compared to those for the mainstream smoke from a Kentucky reference (3R4F) cigarette. Two different test matrices were assessed. Aerosol generated from the e-cigarette was trapped on a Cambridge filter pad, eluted in DMSO and compared to cigarette smoke total particulate matter (TPM), which was generated in the same manner for mutagenicity assessment in the Salmonella assay. Fresh e-cigarette and cigarette smoke aerosols were generated on the Vitrocell ® VC 10 smoking robot and compared using a modified scaled-down 35mm air agar interface (AAI) methodology. E-cigarette aerosol collected matter (ACM) was found to be non-mutagenic in the 85mm plate incorporation Ames assay in strains TA98 and TA100 conducted in accordance with OECD 471, when tested up to 2400μg/plate. Freshly generated e-cigarette aerosol was also found to be negative in both strains after an AAI aerosol exposure, when tested up to a 1L/min dilution for up to 3h. Positive control responses were observed in both strains, using benzo[a]pyrene, 2-nitrofluorene, sodium azide and 2-aminoanthracene in TA98 and TA100 in the presence and absence of metabolic activation respectively. In contrast, cigarette smoke TPM and aerosol from 3R4F reference cigarettes were found to be mutagenic in both tester strains, under comparable test conditions to that of e-cigarette exposure. Limited information exists on the mutagenic activity of captured e-cigarette particulates and whole aerosol AAI approaches. With the lower toxicant burden of e-cigarette aerosols compared to cigarette smoke, it is clear that a more comprehensive Ames package of data should be generated when assessing e-cigarettes, consisting of the standard OECD-five, TA98, TA100, TA1535, TA1537 (or TA97) and E. coli (or TA102). In addition, TA104

A Classroom Modification of the Ames Test.

ERIC Educational Resources Information Center

Yavornitzky, Joseph; Trzeciak, Victor

1979-01-01

A modification of the Ames test for detecting carcinogens and mutagens using a strain of bacteria is described. A suggestion is given for checking the correctness of procedures by using particular hair dyes which have been shown to be mutogenic. (Author/SA)

Mutagenic cost of ribonucleotides in bacterial DNA

PubMed Central

Schroeder, Jeremy W.; Randall, Justin R.; Hirst, William G.; O’Donnell, Michael E.; Simmons, Lyle A.

2017-01-01

Replicative DNA polymerases misincorporate ribonucleoside triphosphates (rNTPs) into DNA approximately once every 2,000 base pairs synthesized. Ribonucleotide excision repair (RER) removes ribonucleoside monophosphates (rNMPs) from genomic DNA, replacing the error with the appropriate deoxyribonucleoside triphosphate (dNTP). Ribonucleotides represent a major threat to genome integrity with the potential to cause strand breaks. Furthermore, it has been shown in the bacterium Bacillus subtilis that loss of RER increases spontaneous mutagenesis. Despite the high rNTP error rate and the effect on genome integrity, the mechanism underlying mutagenesis in RER-deficient bacterial cells remains unknown. We performed mutation accumulation lines and genome-wide mutational profiling of B. subtilis lacking RNase HII, the enzyme that incises at single rNMP residues initiating RER. We show that loss of RER in B. subtilis causes strand- and sequence-context–dependent GC → AT transitions. Using purified proteins, we show that the replicative polymerase DnaE is mutagenic within the sequence context identified in RER-deficient cells. We also found that DnaE does not perform strand displacement synthesis. Given the use of nucleotide excision repair (NER) as a backup pathway for RER in RNase HII-deficient cells and the known mutagenic profile of DnaE, we propose that misincorporated ribonucleotides are removed by NER followed by error-prone resynthesis with DnaE. PMID:29078353

QSAR models to predict mutagenicity of acrylates, methacrylates and alpha,beta-unsaturated carbonyl compounds.

PubMed

Pérez-Garrido, Alfonso; Helguera, Aliuska Morales; Rodríguez, Francisco Girón; Cordeiro, M Natália D S

2010-05-01

The purpose of this study is to develop a quantitative structure-activity relationship (QSAR) model that can distinguish mutagenic from non-mutagenic species with alpha,beta-unsaturated carbonyl moiety using two endpoints for this activity - Ames test and mammalian cell gene mutation test - and also to gather information about the molecular features that most contribute to eliminate the mutagenic effects of these chemicals. Two data sets were used for modeling the two mutagenicity endpoints: (1) Ames test and (2) mammalian cells mutagenesis. The first one comprised 220 molecules, while the second one 48 substances, ranging from acrylates, methacrylates to alpha,beta-unsaturated carbonyl compounds. The QSAR models were developed by applying linear discriminant analysis (LDA) along with different sets of descriptors computed using the DRAGON software. For both endpoints, there was a concordance of 89% in the prediction and 97% confidentiality by combining the three models for the Ames test mutagenicity. We have also identified several structural alerts to assist the design of new monomers. These individual models and especially their combination are attractive from the point of view of molecular modeling and could be used for the prediction and design of new monomers that do not pose a human health risk. 2010 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Mutagenicity of diesel exhaust particles from an engine with differing exhaust after treatments.

PubMed

Shi, X-C; Keane, M J; Ong, T; Li, S-Q; Bugarski, A B

2010-01-01

This study was conducted to investigate the effects of engine operating conditions and exhaust aftertreatments on the mutagenicity of diesel particulate matter (DPM) collected directly in an underground mine environment. A number of after-treatment devices are currently used on diesel engines in mines, but it is critical to determine whether reductions in DPM concentrations result in a corresponding decrease in adverse health effects. An eddy-current dynamometer was used to operate naturally aspirated mechanically controlled engine at several steady-state conditions. The samples were collected when the engine was equipped with a standard muffler, a diesel oxidation catalytic converter, two types of uncatalyzed diesel particulate filter systems, and three types of disposable diesel particulate filter elements. Bacterial gene mutation activity of DPM was tested on acetone extracts using the Ames Salmonella assay. The results indicated strong correlation between engine operating conditions and mutagenic activity of DPM. When the engine was fitted with muffler, the mutagenic activity was observed for the samples collected from light-load, but not heavy-load operating conditions. When the engine was equipped with a diesel oxidation catalyst, the samples did not exhibit mutagenic activity for any of four engine operating conditions. Mutagenic activity was observed for the samples collected when the engine was retrofitted with three types of disposable filters and sintered metal diesel particulate filter and operated at light load conditions. However, those filtration systems substantially reduced the concentration-normalized mutagenic activity from the levels observed for the muffler.

Influence of particulate trap oxidizers on emission of mutagenic compounds by diesel automobiles.

PubMed

Rasmussen, R E; Devillez, G; Smith, L R

1989-06-01

Diesel exhaust particles are known to contain mutagenic and carcinogenic chemicals. The aim of this study was to determine whether, and to what extent, catalytic particulate trap oxidizers on light-duty diesel engines may reduce the emission of particle-associated mutagenic chemicals into the environment. Exhaust particles were collected from Mercedes Benz and Volkswagen diesel automobiles, equipped with or without the manufacturer's exhaust traps, while running on a chassis dynamometer under specified load conditions. Exhaust particles were collected from a dilution tunnel onto 20" X 20" Teflon-coated fiberglass filters. Mutagenesis tests of dichloromethane (DCM) extracts of the particles were conducted using the Ames Salmonella bacterial test system. The mutation rate was calculated in terms of histidine revertants per mile of travel during a set of standard test cycles. With both vehicles the traps produced an 87-92% reduction in the total amount of particulate material collected by the filters. There was no significant change in the specific mutagenic activity (revertants per microgram of DCM particle extract) with or without the traps. These studies support the notion that installation of exhaust traps which reduce particulate emission on diesel-powered vehicles will also reduce the emission of particle-associated mutagenic and carcinogenic materials into the environment.

Mutagenicity of burnt gun propellants

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

Felton, J.S.; Lewis, P.; Knize, M.G.

1989-08-02

The use of the Ames/Salmonella assay as a workplace monitoring method is a long-standing practice at LLNL. This practice has led to the discovery of very mutagenic soot in and around a 4 inch test gun. To the authors' knowledge this is the first finding of mutagenic components in the residue from gun propellants, although there have been numerous reports of mutagenic compounds associated with high explosives -- compounds of entirely different chemical composition (Won et al., 1976). In addition, Ase et al., 1985, analyzed the propellant combustion products of both a M16 rifle and a 105 mm caliber gunmore » with HPLC and GC/MS methods, and found a number of PAHs with known toxicological effects. No biological analysis was done on the residues. Further investigation in our laboratory found that direct acting mutagens where produced upon open burning of the propellants. Small gauge firearms when tested also showed mutagenic residue. Preliminary efforts to identify the mutagenic components estimate that 2-3 compounds are responsible for the biological activity. The identity of these compounds is under investigation. 8 refs., 4 tabs.« less

Paving asphalt products exhibit a lack of carcinogenic and mutagenic activity.

PubMed

Goyak, Katy O; McKee, Richard H; Minsavage, Gary D; McGowan, Claude; Daughtrey, Wayne C; Freeman, James J

2011-10-01

A paving asphalt and a vacuum residuum (derived from crude oil by atmospheric and subsequent vacuum distillation and used as a blend stock for asphalt) were tested in skin carcinogenesis assays in mice and in optimized Ames assays for mutagenic activity. In the skin cancer tests, each substance was applied twice weekly for 104 weeks to the clipped backs of groups of 50 male C3H mice. Neither the paving asphalt nor the vacuum residuum (30% weight/volume and 75% weight/weight in US Pharmacopeia mineral oil, respectively) produced any tumors. The positive control benzo[a]pyrene (0.05% w/v in toluene) induced tumors in 46 of 50 mice, demonstrating the effectiveness of the test method. Salmonella typhimurium tester strain TA98 was used in the optimized Ames assay to evaluate mutagenic potential. Dimethylsulfoxide (DMSO) extractions of the substances were not mutagenic when tested up to toxic limits. Thus, under the conditions of these studies, neither the paving asphalt nor the vacuum residuum was carcinogenic or mutagenic.

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

PubMed

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.

Novel naïve Bayes classification models for predicting the chemical Ames mutagenicity.

PubMed

Zhang, Hui; Kang, Yan-Li; Zhu, Yuan-Yuan; Zhao, Kai-Xia; Liang, Jun-Yu; Ding, Lan; Zhang, Teng-Guo; Zhang, Ji

2017-06-01

Prediction of drug candidates for mutagenicity is a regulatory requirement since mutagenic compounds could pose a toxic risk to humans. The aim of this investigation was to develop a novel prediction model of mutagenicity by using a naïve Bayes classifier. The established model was validated by the internal 5-fold cross validation and external test sets. For comparison, the recursive partitioning classifier prediction model was also established and other various reported prediction models of mutagenicity were collected. Among these methods, the prediction performance of naïve Bayes classifier established here displayed very well and stable, which yielded average overall prediction accuracies for the internal 5-fold cross validation of the training set and external test set I set were 89.1±0.4% and 77.3±1.5%, respectively. The concordance of the external test set II with 446 marketed drugs was 90.9±0.3%. In addition, four simple molecular descriptors (e.g., Apol, No. of H donors, Num-Rings and Wiener) related to mutagenicity and five representative substructures of mutagens (e.g., aromatic nitro, hydroxyl amine, nitroso, aromatic amine and N-methyl-N-methylenemethanaminum) produced by ECFP_14 fingerprints were identified. We hope the established naïve Bayes prediction model can be applied to risk assessment processes; and the obtained important information of mutagenic chemicals can guide the design of chemical libraries for hit and lead optimization. Copyright © 2017 Elsevier B.V. All rights reserved.

Mutagenic and genotoxic potential of direct electric current in Escherichia coli and Salmonella thyphimurium strains.

PubMed

Gomes, Marina das Neves; Cardoso, Janine Simas; Leitão, Alvaro Costa; Quaresma, Carla Holandino

2016-05-01

Direct electric current has several therapeutic uses such as antibacterial and antiprotozoal action, tissues scarring and regeneration, as well as tumor treatment. This method has shown promising results in vivo and in vitro, with significant efficacy and almost no side effects. Considering lack of studies regarding direct electric current mutagenic and/or genotoxic effects, the present work evaluated both aspects by using five different bacterial experimental assays: survival of repair-deficient mutants, Salmonella-histidine reversion mutagenesis (Ames test), forward mutations to rifampicin resistance, phage reactivation, and lysogenic induction. In these experimental conditions, cells were submitted to an approach that allows evaluation of anodic, cathodic, and electro-ionic effects generated by 2 mA of direct electric current, with doses ranging from 0.36 to 3.60 Coulombs. Our results showed these doses did not induce mutagenic or genotoxic effects. © 2016 Wiley Periodicals, Inc.

Mutagenicity of pan residues and gravy from fried meat.

PubMed

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.

Mutagenic activation reduces carcinogenic activity of ortho-aminoazotoluene for mouse liver.

PubMed

Ovchinnikova, L P; Bogdanova, L A; Kaledin, V I

2013-03-01

Pentachlorophenol (aromatic amine and azo stain metabolic stimulation inhibitor) reduced the hepatocarcinogenic activity of 4-aminoazobenzene and reduced that of ortho-aminoazotoluene in suckling mice. Both 4-aminoazobenzene and ortho-aminoazotoluene exhibited mutagenic activity in Ames' test in vitro on S. typhimurium TA 98 strain with activation with liver enzymes; this mutagenic activity was similarly suppressed by adding pentachlorophenol into activation medium. Induction of xenobiotic metabolism enzymes, stimulating the mutagenic activity of ortho-aminoazotoluene, suppressed its carcinogenic effect on mouse liver. Hence, ortho-aminotoluene (the initial compound), but not its mutagenic metabolites, was the direct active hepatocarcinogen for mice.

Development, qualification, validation and application of the Ames test using a VITROCELL® VC10® smoke exposure system.

PubMed

Fowler, Kathy; Fields, Wanda; Hargreaves, Victoria; Reeve, Lesley; Bombick, Betsy

2018-01-01

The Ames test has established use in the assessment of potential mutagenicity of tobacco products but has generally been performed using partitioned exposures (e.g. total particulate matter [TPM], gas vapor phase [GVP]) rather than whole smoke (WS). The VITROCELL ® VC10 ® smoke exposure system offers multiple platforms for air liquid interface (ALI), or air agar interface (AAI) in the case of the Ames test exposure to mimic in vivo -like conditions for assessing the toxicological impact of fresh WS in in vitro assays. The goals of this study were to 1) qualify the VITROCELL ® VC10 ® to demonstrate functionality of the system, 2) develop and validate the Ames test following WS exposure with the VITROCELL ® VC10 ® and 3) assess the ability of the Ames test to differentiate between a reference combustible product (3R4F Kentucky reference cigarette) and a primarily tobacco heating product (Eclipse). Based on critical function assessments, the VITROCELL ® VC10 ® was demonstrated to be fit for the purpose of consistent generation of WS. Assay validation was conducted for 5 bacterial strains (TA97, TA98, TA100, TA1535 and TA102) and reproducible exposure-related changes in revertants were observed for TA98 and TA100 in the presence of rat liver S-9 following exposure to 3R4F WS. In the comparative studies, exposure-related changes in in vitro mutagenicity following exposure of TA98 and TA100 in the presence of S9 to both 3R4F and Eclipse WS were observed, with the response for Eclipse being significantly less than that for 3R4F (p < 0.001) which is consistent with the fewer chemical constituents liberated by primarily-heating the product.

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

PubMed

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

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

PubMed

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.

USE OF BIOASSAY-DIRECTED CHEMICAL ANALYSIS FOR IDENTIFYING MUTAGENIC COMPOUNDS IN URBAN AIR AND COMBUSTION EMISSIONS

EPA Science Inventory

Bioassay-directed chemical analysis fractionation has been used for 30 years to identify mutagenic classes of compounds in complex mixtures. Most studies have used the Salmonella (Ames) mutagenicity assay, and we have recently applied this methodology to two standard reference sa...

Mutagenicity and genotoxicity of coal fly ash water leachate

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

Chakraborty, R.; Mukherjee, A.

2009-03-15

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 metalsmore » - 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 significantconcentration-dependent increases in DNA damage in whole blood cells, lymphocytes, and in Nicotiana plants. The comet parameters show increases in tail DNA percentage (%), tail length (mu m), 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.« less

A method for the detection of protein-bound mutagens in food.

PubMed

Ibe, F I; Blowers, S D; Anderson, D; Massey, R

1994-01-01

To investigate the possible presence of protein-bound mutagens in food an analytical procedure has been devised in which the sample is enzymically hydrolysed, fractionated by HPLC and examined by a modified liquid incubation Ames assay. To validate the method MeIQx was added, as a model compound, to beefburger and a recovery of 82% obtained. The limit of detection for protein-bound mutagens was 1 microgram/kg, expressed as equivalents of MeIQx. No detectable mutagenicity was observed when the procedure was applied to samples of well cooked beefburger, irradiated chicken or mycoprotein.

Exposure to mutagenic chemicals in foundry and urban environments.

PubMed

Barański, B; Palus, J; Janik-Spiechowicz, E

1989-01-01

The study was aimed at the estimation of occupational exposure to mutagenic substances in a piston-ring foundry. The following samples were examined: solid phase of aerosol from the foundry and from different places of urban environment together with the foundry workers' urine collected during the 8-hour shift. The mutagenic substances were extracted from the collected material with acetone or concentrated with XAD-2 resin. The mutagenic property was estimated with the Ames' test using S. typhimurium strain TA98 without and with S9 fraction. The highest mutagenic activity was found at the following work-posts: caster, moulder, steerer of an induction furnace, and smelter and in the office rooms and in the flat occupied by heavy smokers. The mutagenic activity of aerosol at some other productive workposts in the foundry was similar to the mutagenic activity of aerosol in the office and flat rooms occupied by nonsmokers or in the street in Lodz. The mutagenic activity of urine from foundry workers was not correlated with the level of the occupational inhalation exposure to the mutagenic substances, however, the mutagenic activity of urine from smoking workers was about 10-20 times higher than from nonsmokers.

Mutagenicity and antimutagenicity of extracts of three spices and a medicinal plant in Thailand.

PubMed

Higashimoto, M; Purintrapiban, J; Kataoka, K; Kinouchi, T; Vinitketkumnuen, U; Akimoto, S; Matsumoto, H; Ohnishi, Y

1993-11-01

Three kinds of spices (caraway, coriander and black pepper seeds) and a medicinal plant called 'tong tak' in Thai (Baliospermum axillar, a species of the spurge family) were fractionated into hot water, methanol and hexane extracts. These extracts were not mutagenic for Salmonella typhimurium strains TA98 and TA100 by the Ames assay. However, when the extracts were treated with nitrite, samples of the water and methanol extracts were mutagenic for strain TA100 without metabolic activation. The mutagenicity of the nitrite-treated methanol and hot water extracts of black pepper was highest (8380 and 22,200 His+ per 0.1 g of spice powder, respectively), and that of the nitrite-treated hot water extracts of caraway and tong tak was moderate. The hot water extracts were examined for their antimutagenic activity against mutagenicity induced by various carcinogens by the Ames assay, using the preincubation technique. The tested samples (equivalent to 1-2 mg of spice powder) reduced the mutagenicity induced by 2.7 nmole (397 ng) of N-methyl-N'-nitro-N-nitrosoguanidine by more than 84%, and that induced by dimethylnitrosamine (1.48 mg) or ICR-170 (10 ng) by 30-60%. However, they did not inhibit the mutagenic activity of 1-nitropyrene, 3-nitrofluoranthene, AF-2, methyl methanesulfonate, N-ethyl-N'-nitro-N-nitrosoguanidine, 2-aminoanthracene, 2-acetylaminofluorene, benzo[a]pyrene or IQ.

40 CFR 799.9510 - TSCA bacterial reverse mutation test.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the Salmonella/Mammalian-Microsome Mutagenicity Test. Mutation Research. 31, 347-364 (1975). (2) Maron, D.M. and Ames, B.N. Revised Methods for the Salmonella Mutagenicity Test. Mutation Research. 113... Bridges, B.A. Use of a Simplified Fluctuation Test to Detect Low Levels of Mutagens. Mutation Research. 38...

40 CFR 799.9510 - TSCA bacterial reverse mutation test.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the Salmonella/Mammalian-Microsome Mutagenicity Test. Mutation Research. 31, 347-364 (1975). (2) Maron, D.M. and Ames, B.N. Revised Methods for the Salmonella Mutagenicity Test. Mutation Research. 113... Bridges, B.A. Use of a Simplified Fluctuation Test to Detect Low Levels of Mutagens. Mutation Research. 38...

40 CFR 799.9510 - TSCA bacterial reverse mutation test.

Code of Federal Regulations, 2012 CFR

2012-07-01

... the Salmonella/Mammalian-Microsome Mutagenicity Test. Mutation Research. 31, 347-364 (1975). (2) Maron, D.M. and Ames, B.N. Revised Methods for the Salmonella Mutagenicity Test. Mutation Research. 113... Bridges, B.A. Use of a Simplified Fluctuation Test to Detect Low Levels of Mutagens. Mutation Research. 38...

The mutagenicity of cassava (Manihot esculenta Crantz) preparations.

PubMed

De Meester, C; Rollmann, B; Mupenda, K; Mary, Y

1990-01-01

Different cassava products were found to contain mutagenic activities in the Ames test. This paper describes how the flavonol quercetin is released during the cooking of fresh cassava leaves, following a process very similar to culinary habits. The hydrolysis of the glucoside(s) and the release of free quercetin has been followed by the monitoring of mutagenic activities with a simultaneous isolation and purification by thin-layer chromatography. The fluorodensitometric method applied revealed that fresh leaves contained about 1300 mg quercetin per kg wet weight, of which 800 mg were released during a normal cooking process.

40 CFR 799.9510 - TSCA bacterial reverse mutation test.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Mutagenicity Test. Mutation Research. 31, 347-364 (1975). (2) Maron, D.M. and Ames, B.N. Revised Methods for the Salmonella Mutagenicity Test. Mutation Research. 113, 173-215 (1983). (3) Gatehouse, D., Haworth... Fluctuation Test to Detect Low Levels of Mutagens. Mutation Research. 38, 33-42 (1976). (10) Hubbard, S.A...

Mutagenicity of adsorbates to a copper-phthalocyanine derivative recovered from municipal river water.

PubMed

Sayato, Y; Nakamuro, K; Ueno, H; Goto, R

1990-12-01

Blue cotton, bearing a covalently bound copper-phthalocyanine derivative capable of adsorbing polycyclic aromatic hydrocarbons (PAHs) over 3 rings, was applied to recover mutagens from the Katsura River which is a tributary of the Yodo River. The Ames Salmonella/microsome assay with TA98 and TA100 of the blue cotton concentrate recovered from the river water demonstrated indirect mutagenicity toward TA98. The subfractions separated by Sephadex G-25 gel chromatography also showed direct mutagenicity in strains YG1021 and YG1024, the nitroreductase- and O-acetyltransferase-overproducing derivatives of TA98; this activity was greatly increased by the addition of S9 mix, especially in YG1024. However, these subfractions were less mutagenic with TA98NR or TA98/1,8-DNP6, regardless of whether S9 mix was present or not. The behaviors of these mutagenic activities therefore suggested that frameshift mutagens of both directly mutagenic nitroarenes and indirectly mutagenic aminoarenes were present in the blue cotton concentrate from the river water.

Mutagenicity of biodiesel or diesel exhaust particles and the effect of engine operating conditions.

PubMed

Kisin, Elena R; Shi, X C; Keane, Michael J; Bugarski, Aleksandar B; Shvedova, Anna A

2013-03-01

Changing the fuel supply from petroleum based ultra-low sulfur diesel (ULSD) to biodiesel and its blends is considered by many to be a viable option for controlling exposures to particulate material (PM). This is critical in the mining industry where approximately 28,000 underground miners are potentially exposed to relatively high concentrations of diesel particulate matter (DPM). This study was conducted to investigate the mutagenic potential of diesel engine emissions (DEE) from neat (B100) and blended (B50) soy-based fatty acid methyl ester (FAME) biodiesel in comparison with ULSD PM using different engine operating conditions and exhaust aftertreatment configurations. The DPM samples were collected for engine equipped with either a standard muffler or a combination of the muffler and diesel oxidation catalytic converter (DOC) that was operated at four different steady-state modes. Bacterial gene mutation activity of DPM was tested on the organic solvent extracts using the Ames Salmonella assay. The results indicate that mutagenic activity of DPM was strongly affected by fuels, engine operating conditions, and exhaust aftertreatment systems. The mutagenicity was increased with the fraction of biodiesel in the fuel. While the mutagenic activity was observed in B50 and B100 samples collected from both light-and heavy-load operating conditions, the ULSD samples were mutagenic only at light-load conditions. The presence of DOC in the exhaust system resulted in the decreased mutagenicity when engine was fueled with B100 and B50 and operated at light-load conditions. This was not the case when engine was fueled with ULSD. Heavy-load operating condition in the presence of DOC resulted in a decrease of mutagenicity only when engine was fueled with B50, but not B100 or ULSD. Therefore, the results indicate that DPM from neat or blended biodiesel has a higher mutagenic potency than that one of ULSD. Further research is needed to investigate the health effect of biodiesel

Mutagenicity of biodiesel or diesel exhaust particles and the effect of engine operating conditions

PubMed Central

Kisin, Elena R; Shi, X.C; Keane, Michael J; Bugarski, Aleksandar B; Shvedova, Anna A

2015-01-01

Background Changing the fuel supply from petroleum based ultra-low sulfur diesel (ULSD) to biodiesel and its blends is considered by many to be a viable option for controlling exposures to particulate material (PM). This is critical in the mining industry where approximately 28,000 underground miners are potentially exposed to relatively high concentrations of diesel particulate matter (DPM). This study was conducted to investigate the mutagenic potential of diesel engine emissions (DEE) from neat (B100) and blended (B50) soy-based fatty acid methyl ester (FAME) biodiesel in comparison with ULSD PM using different engine operating conditions and exhaust aftertreatment configurations. Methods The DPM samples were collected for engine equipped with either a standard muffler or a combination of the muffler and diesel oxidation catalytic converter (DOC) that was operated at four different steady-state modes. Bacterial gene mutation activity of DPM was tested on the organic solvent extracts using the Ames Salmonella assay. Results The results indicate that mutagenic activity of DPM was strongly affected by fuels, engine operating conditions, and exhaust aftertreatment systems. The mutagenicity was increased with the fraction of biodiesel in the fuel. While the mutagenic activity was observed in B50 and B100 samples collected from both light-and heavy-load operating conditions, the ULSD samples were mutagenic only at light-load conditions. The presence of DOC in the exhaust system resulted in the decreased mutagenicity when engine was fueled with B100 and B50 and operated at light-load conditions. This was not the case when engine was fueled with ULSD. Heavy-load operating condition in the presence of DOC resulted in a decrease of mutagenicity only when engine was fueled with B50, but not B100 or ULSD. Conclusions Therefore, the results indicate that DPM from neat or blended biodiesel has a higher mutagenic potency than that one of ULSD. Further research is needed to

Heptyl prodigiosin, a bacterial metabolite, is antimalarial in vivo and non-mutagenic in vitro.

PubMed

Lazaro, J Enrico H; Nitcheu, Josiane; Predicala, Rey Z; Mangalindan, Gina C; Nesslany, Fabrice; Marzin, Daniel; Concepcion, Gisela P; Diquet, Bertrand

2002-12-01

Heptyl prodigiosin was purified from a culture of alpha-proteobacteria isolated from a marine tunicate collected in Zamboanga, Philippines, as part of a program to screen natural products for antiparasitic activity. An in vitro antimalarial activity similar to that of quinine was found against the chloroquine-sensitive strain Plasmodium falciparum 3D7. The in vitro antimalarial activity was about 20 times the in vitro cytotoxic activity against L5178Y mouse lymphocytes. A single subcutaneous administration of 5 and 20 mg/kg significantly extended survival of P. berghei ANKA strain-infected mice but also caused sclerotic lesions at the site of injection. A single administration by gavage of 50 mg/kg did not increase survival time. The compound was not found to be mutagenic using in vitro micromethods for the Ames Salmonella typhimurium assay and the micronucleus assay using L5178Y mouse lymphoma cells.

Mutagenicity of diesel exhaust particles and oil shale particles dispersed in lecithin surfactant.

PubMed

Wallace, W E; Keane, M J; Hill, C A; Xu, J; Ong, T M

1987-01-01

Diesel exhaust particulate material from exhaust pipe scrapings of two trucks, diluted automobile diesel exhaust particulate material collected on filters, and two oil shale ores were prepared for the Ames mutagenicity assay by dichloromethane (DCM) extraction, by dispersion into 0.85% saline, or by dispersion into dipalmitoyl lecithin (DPL) emulsion in saline. Salmonella typhimurium TA98 was used to detect frameshift mutagens in the samples. Samples of diesel soot gave positive mutagenic responses with both DCM extraction and DPL dispersion, with the DPL dispersion giving higher results in some cases. The results suggest that possible mutagens associated with inhaled particles may be dispersed or solubilized into the phospholipid component of pulmonary surfactant and become active in such a phase.

Evaluation of Genotoxic and Mutagenic Activity of Organic Extracts from Drinking Water Sources

PubMed Central

Guan, Ying; Wang, Xiaodong; Wong, Minghung; Sun, Guoping; An, Taicheng; Guo, Jun

2017-01-01

An increasing number of industrial, agricultural and commercial chemicals in the aquatic environment lead to various deleterious effects on organisms, which is becoming a serious global health concern. In this study, the Ames test and SOS/umu test were conducted to investigate the potential genotoxicity and mutagenicity caused by organic extracts from drinking water sources. Organic content of source water was extracted with XAD-2 resin column and organic solvents. Four doses of the extract equivalent to 0.25, 0.5, 1 and 2L of source water were tested for toxicity. All the water samples were collected from six different locations in Guangdong province. The results of the Ames test and SOS/umu test showed that all the organic extracts from the water samples could induce different levels of DNA damage and mutagenic potentials at the dose of 2 L in the absence of S9 mix, which demonstrated the existence of genotoxicity and mutagenicity. Additionally, we found that Salmonella typhimurium strain TA98 was more sensitive for the mutagen. Correlation analysis between genotoxicity, Organochlorine Pesticides (OCPs) and Polycyclic Aromatic Hydrocarbons (PAHs) showed that most individual OCPs were frame shift toxicants in drinking water sources, and there was no correlation with total OCPs and PAHs. PMID:28125725

MUTAGENICITY OF TEFLON-COATED GLASS FIBER FILTERS: A POTENTIAL PROBLEM AND SOLUTIONS

EPA Science Inventory

Teflon-coated glass fiber filters, used in studies of airborne particulate matter, were tested for mutagenic activity using the Salmonella/mammalian-microsome (Ames) assay. For each sample, eight blank filters were simultaneously extracted with dichloromethane (DCM), and the extr...

GENERAL ENHANCEMENT OF MUTAGENIC POTENCY OF VARIOUS MUTAGENS DUE TO DELETED GENES IN THE ΔuvrB STRAINS TA 98 AND TA 100 OF SALMONELLA COMPARED WITH STRAINS CONTAINING ONLY A POINT MUTATION IN uvrB

EPA Science Inventory

The two most common strains used in Ames mutagenicity assays, TA98 and TA 100, contain a �uvrB mutation designed to enhance the mutagenicity of compounds, presumably due to the loss of the nucleotide excision repair system. We showed previously that the �uvrB mutations in these s...

Mutagenicity assessment of airborne particles in Mexico City

NASA Astrophysics Data System (ADS)

Villalobos-Pietrini, Rafael; Blanco, Salvador; Gomez-Arroyo, Sandra

The Ames's TA98 strain of Salmonella typhimurium with and without mammalian metabolic activation was used to detect the mutagenic activity of organic chemicals associated with airborne particles. Two kinds of particles: total suspended (TSP) and those particles with an aerodynamic diameter of 10 μm or smaller (PM 10) were collected in glass fiber filters using high-volume samplers during the dry season (December 1989-March 1990) in the Metropolitan Area of Mexico City at five stations of the air quality network belonging to the Ministry of Social Development. Although the highest mass concentrations of particles were obtained from the Northeastern and Southeastern areas, the largest frequency of mutations was found Downtown which indicated that vehicle exhaust was an important source. Contrary to what was expected, the mutagenic responses were higher for PM10 than for TSP samples. On the other hand, the microsome activation increased significantly the mutagenic activity of the complex mixture, which hinted at the presence of higher amounts of indirect (or promutagens) than direct mutagens both for TSP and PM10.

Extreme testing of undiluted e-cigarette aerosol in vitro using an Ames air-agar-interface technique.

PubMed

Thorne, D; Hollings, M; Seymour, A; Adamson, J; Dalrymple, A; Ballantyne, M; Gaca, M

2018-04-01

There is a growing consensus that e-cigarettes hold the potential for reducing the harm associated with cigarette smoking. Recently published studies have reported in vitro testing of e-cigarettes, demonstrating reduced toxicological and biological effects. Few studies however have reported the use of e-cigarettes under extreme testing conditions. To assess the full mutagenic potential of a commercially available electronic-cigarette (Vype ePen), this study investigated the delivery of aerosol under extreme conditions, using a scaled-down 35 mm plate Ames bacterial reverse mutagenicity assay. S. typhimurium strains TA98, TA100, TA97, TA104 and E. coli WP2 uvrA pKM101 with or without metabolic activation (S9), were employed. Using a modified Vitrocell VC 10 exposure system 0, 180, 360, 540, 720 or 900 puffs of undiluted e-cigarette aerosol was generated and delivered to bacterial cultures aligned to reported human consumption data. The results demonstrate that no mutagenic activity was observed in any strain under any test condition even when exposed to 900 puffs of undiluted e-cigarette aerosols +/- S9. Positive control responses were observed in all strains +/- S9. Nicotine assessments demonstrated an increased and consistent aerosol delivery, with calculated maximum doses of ∼1 mg/mL delivery of nicotine. These data demonstrate the validity of this unique testing approach and adds further information to the growing weight of evidence that e-cigarettes offer substantially reduced exposure when compared to conventional cigarette smoke. For future in vitro assessments of next generation tobacco and nicotine products, the generation, delivery and testing of undiluted aerosols can now be considered. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

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

PubMed

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.

Hyperforin Exhibits Antigenotoxic Activity on Human and Bacterial Cells.

PubMed

Imreova, Petronela; Feruszova, Jana; Kyzek, Stanislav; Bodnarova, Kristina; Zduriencikova, Martina; Kozics, Katarina; Mucaji, Pavel; Galova, Eliska; Sevcovicova, Andrea; Miadokova, Eva; Chalupa, Ivan

2017-01-21

Hyperforin (HF), a substance that accumulates in the leaves and flowers of Hypericum perforatum L. (St. John's wort), consists of a phloroglucinol skeleton with lipophilic isoprene chains. HF exhibits several medicinal properties and is mainly used as an antidepressant. So far, the antigenotoxicity of HF has not been investigated at the level of primary genetic damage, gene mutations, and chromosome aberrations, simultaneously. The present work is designed to investigate the potential antigenotoxic effects of HF using three different experimental test systems. The antigenotoxic effect of HF leading to the decrease of primary/transient promutagenic genetic changes was detected by the alkaline comet assay on human lymphocytes. The HF antimutagenic effect leading to the reduction of gene mutations was assessed using the Ames test on the standard Salmonella typhimurium (TA97, TA98, and TA100) bacterial strains, and the anticlastogenic effect of HF leading to the reduction of chromosome aberrations was evaluated by the in vitro mammalian chromosome aberration test on the human tumor cell line HepG2 and the non-carcinogenic cell line VH10. Our findings provided evidence that HF showed antigenotoxic effects towards oxidative mutagen zeocin in the comet assay and diagnostic mutagen (4-nitroquinoline-1-oxide) in the Ames test. Moreover, HF exhibited an anticlastogenic effect towards benzo(a)pyrene and cisplatin in the chromosome aberration test.

Identification of formaldehyde as the metabolite responsible for the mutagenicity of methyl tertiary-butyl ether in the activated mouse lymphoma assay.

PubMed

Mackerer, C R; Angelosanto, F A; Blackburn, G R; Schreiner, C A

1996-09-01

Methyl tertiary-butyl ether (MTBE), which is added to gasoline as an octane enhancer and to reduce automotive emissions, has been evaluated in numerous toxicological tests, including those for genotoxicity. MTBE did not show any mutagenic potential in the Ames bacterial assay or any clastogenicity in cytogenetic tests. However, it has been shown to be mutagenic in an in vitro gene mutation assay using mouse lymphoma cells when tested in the presence, but not in the absence, of a rat liver-derived metabolic activation system (S-9). In the present study, MTBE was tested to determine if formaldehyde, in the presence of the S-9, was responsible for the observed mutagenicity. A modification of the mouse lymphoma assay was employed which permits determination of whether a suspect material is mutagenic because it contains or is metabolized to formaldehyde. In the modified assay, the enzyme formaldehyde dehydrogenase (FDH) and its co-factor, NAD+ are added in large excess during the exposure period so that any formaldehyde produced in the system is rapidly converted to formic acid which is not genotoxic. An MTBE dose-responsive increase in the frequency of mutants and in cytotoxicity occurred without FDH present, and this effect was greatly reduced in the presence of FDH NAD+. The findings clearly demonstrate that formaldehyde derived from MTBE is responsible for mutagenicity of MTBE in the activated mouse lymphoma assay. Furthermore, the results suggest that the lack of mutagenicity/clastogenicity seen with MTBE in other in vitro assays might have resulted from inadequacies in the test systems employed for those assays.

THE DELTA UVRB MUTATIONS IN THE AMES STRAINS OF SALMONELLA SPAN 15-119 GENES

EPA Science Inventory

Abstract

The 4uvrB mutationesent in strains of Salmonella enterica Typhirnurium used commonly in the Salmonella (Ames) mutagenicity assay were isolated independently on separate occasions: chl-1005 (bio uvrBgal) for the hisG46-containing strains TA1535 and TA100; chl- 10...

Mutagenicity of fume particles from metal arc welding on stainless steel in the Salmonella/microsome test.

PubMed

Maxild, J; Andersen, M; Kiel, P

1978-01-01

Mutagenic activity of fume particles produced by metal arc welding on stainless steel (ss) is demonstrated by using the Salmonella/microsome mutagenicity test described by Ames et al., with strain TA100 (base-pair substitution) and TA98 (frame-shift reversion). Results of a representative but limited selection of processes and materials show that mutagenic activity is a function of process and process parameters. Welding on stainless steel produces particles that are mutagenic, whereas welding on mild steel (ms) produces particles that are not. Manual metal arc (MMA) welding on stainless steel produces particles of higher mutagenic activity than does metal inert gas (MIG) welding, and fume particles produced by MIG welding under short-arc transfer. Further studies of welding fumes (both particles and gases) must be performed to determine process parameters of significance for the mutagenic activity.

A Novel Strategy to Predict Carcinogenicity of Antiparasitics Based on a Combination of DNA Lesions and Bacterial Mutagenicity Tests

PubMed Central

Liu, Qianying; Lei, Zhixin; Zhu, Feng; Ihsan, Awais; Wang, Xu; Yuan, Zonghui

2017-01-01

Genotoxicity and carcinogenicity testing of pharmaceuticals prior to commercialization is requested by regulatory agencies. The bacterial mutagenicity test was considered having the highest accuracy of carcinogenic prediction. However, some evidences suggest that it always results in false-positive responses when the bacterial mutagenicity test is used to predict carcinogenicity. Along with major changes made to the International Committee on Harmonization guidance on genotoxicity testing [S2 (R1)], the old data (especially the cytotgenetic data) may not meet current guidelines. This review provides a compendium of retrievable results of genotoxicity and animal carcinogenicity of 136 antiparasitics. Neither genotoxicity nor carcinogenicity data is available for 84 (61.8%), while 52 (38.2%) have been evaluated in at least one genotoxicity or carcinogenicity study, and only 20 (14.7%) in both genotoxicity and carcinogenicity studies. Among 33 antiparasitics with at least one old result in in vitro genotoxicity, 15 (45.5%) are in agreement with the current ICH S2 (R1) guidance for data acceptance. Compared with other genotoxicity assays, the DNA lesions can significantly increase the accuracy of prediction of carcinogenicity. Together, a combination of DNA lesion and bacterial tests is a more accurate way to predict carcinogenicity. PMID:29170735

Mutagenicity of particulate emissions from the M16 rifle: variation with particle size.

PubMed

Palmer, W G; Andrews, A W; Mellini, D; Terra, J A; Hoffmann, F J; Hoke, S H

1994-08-01

Emissions generated by firing the M16 rifle with the propellant WC844 in a combustion chamber designed to simulate conditions of actual use were tested for mutagenic activity in the Salmonella/Ames assay. Dimethyl sulfoxide extracts of emissions collected from either the breech or muzzle end of the rifle were mutagenic in three strains of Salmonella (TA1537, TA1538, and TA98) both in the presence and absence of metabolic activation systems (S9). The extracts were negative in strains TA100 and TA102. Aerosols generated by firing the M16 rifle were fractionated according to aerodynamic diameter. Submicrometer particles were far more mutagenic than particles with aerodynamic diameters between 1 and 15 microns. The mutagens associated with the smaller particles were more active in the presence of S9, while extracts of larger particles were as active, or more active, in the absence of S9. Heavier particles, which settled rapidly out of the airstream, were not mutagenic.

In vitro genotoxicity of neutral red after photo-activation and metabolic activation in the Ames test, the micronucleus test and the comet assay.

PubMed

Guérard, Melanie; Zeller, Andreas; Singer, Thomas; Gocke, Elmar

2012-07-04

Neutral red (Nr) is relatively non-toxic and is widely used as indicator dye in many biological test systems. It absorbs visible light and is known to act as a photosensitizer, involving the generation of reactive oxygen species (type-I reaction) and singlet oxygen (type-II reaction). The mutagenicity of Nr was determined in the Ames test (with Salmonella typhimurium strains TA1535, TA97, TA98, TA98NR, TA100, and TA102) with and without metabolic activation, and with and without photo-activation on agar plates. Similarly to the situation following metabolic activation, photo-mutagenicity of Nr was seen with all Salmonella strains tested, albeit with different effects between these strains. To our knowledge, Nr is the only photo-mutagen showing such a broad action. Since the effects are also observed in strains not known to be responsive to ROS, this indicates that ROS production is not the sole mode of action that leads to photo-genotoxicity. The reactive species produced by irradiation are short-lived as pre-irradiation of an Nr solution did not produce mutagenic effects when added to the bacteria. In addition, mutagenicity in TA98 following irradiation was stronger than in the nitroreductase-deficient strain TA98NR, indicating that nitro derivatives that are transformed by bacterial nitroreductase to hydroxylamines appear to play a role in the photo-mutagenicity of Nr. Photo-genotoxicity of Nr was further investigated in the comet assay and micronucleus test in L5178Y cells. Concentration-dependent increases in primary DNA damage and in the frequency of micronuclei were observed after irradiation. Copyright © 2012 Elsevier B.V. All rights reserved.

Factors influencing the mutagenic activity of the colon carcinogen 1,2-dimethylhydrazine in Salmonella typhimurium strain TA 1535 in vitro.

PubMed

Kerklaan, P R; Bouter, S; Mohn, G R

1984-04-01

The colon carcinogen 1,2-dimethylhydrazine (SMDH), a non-mutagen in the standard Ames assay, has been shown in previous experiments to become weakly mutagenic in Salmonella TA 1535 in vitro, when specific test conditions were used. The present studies were performed to determine more precisely the nature of metabolic factors and experimental conditions for optimal mutagenesis of SDMH in the same strain of Salmonella. First, it was confirmed that both the presence of rat liver S9 fractions (25 microliters/ml incubation mixture) and prolonged pre-incubation periods in liquid medium of at least 120 min were necessary to elicit SDMH mutagenesis. In contrast to results obtained with dimethylnitrosamine, which served as a model compound for the activation through oxidative, cytochrome P-450- and NADPH-dependent enzymatic processes, the activation of SDMH to mutagenic factors was not dependent on the presence of NADPH: in fact, NADPH strongly reduced the SDMH-induced mutation yields. It was also observed that growth of the indicator bacteria is an important prerequisite for mutation induction by SDMH. Aminoacetonitrile and disulfiram, two inhibitors of SDMH metabolism and carcinogenicity in mammals, also strongly inhibited SDMH mutagenesis in the present in vitro assay. It can, therefore, be concluded that (i) the right test protocol is of crucial importance for the detection of SDMH as a bacterial mutagen, and (ii) that activation pathways in vitro are (partially) different from presumed in vivo metabolism and activation.

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

EPA Science Inventory

The genotoxicity of ambient outdoor air, a review: Salmonella mutagenicity

Abstract
Mutagens in urban air pollution come from anthropogenic sources (especially combustion sources) and are products of airborne chemical reactions. Bacterial mutation tests have been used ...

Correlations of water quality parameters with mutagenicity of chlorinated drinking water samples.

PubMed

Schenck, Kathleen M; Sivaganesan, Mano; Rice, Glenn E

2009-01-01

Adverse health effects that may result from chronic exposure to mixtures of disinfection by-products (DBPs) present in drinking waters may be linked to both the types and concentrations of DBPs present. Depending on the characteristics of the source water and treatment processes used, both types and concentrations of DBPs found in drinking waters vary substantially. The composition of a drinking-water mixture also may change during distribution. This study evaluated the relationships between mutagenicity, using the Ames assay, and water quality parameters. The study included information on treatment, mutagenicity data, and water quality data for source waters, finished waters, and distribution samples collected from five full-scale drinking water treatment plants, which used chlorine exclusively for disinfection. Four of the plants used surface water sources and the fifth plant used groundwater. Correlations between mutagenicity and water quality parameters are presented. The highest correlation was observed between mutagenicity and the total organic halide concentrations in the treated samples.

Mutagenic activity and heterocyclic amine content of heated foods

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

Knize, M.G.; Johansson, M.; Jones, A.L.

1994-12-31

Cooked foods were extracted and analyzed for mutagenic activity and assayed for known heterocyclic amines (HAs) by the Ames/Salmonella test and HPLC, respectively. Fried meats contain HAs (predominantly PhIP, MeIQx, DiMeIQx, and A{alpha}C) that are potent promutagens in bacteria, mutagenic in cultured mammalian cells, and carcinogenic in rodents and in nonhuman primates. Meats contain levels ranging from undetectable (< 0.1 ppb) to 50 ppb of known HAs when fried at temperatures from 190 to 250{degrees}C. These identified compounds are responsible for ca 75% of the measured mutagenic activity in Salmonella strain TA98. Barbecued beef and chicken have up to severalmore » thousand TA98 revertants per gram (rev/g) of cooked meat, with only ca 30% of the mutagenic activity accounted for by known heterocyclic amines. Some heated nonmeat foods also contain potent mutagenic activity. Toasted breads, cereals and snack foods have 0 to 10 TA98 rev/g, but overtoasting yields up to 40 rev/g, wheat and gluten-containing products are associated with higher activity. Grain-based coffee-substitute powders and instant coffees have 190 to 380 rev/g in TA98, and 1100 to 4000 rev/g in strain YG1024. The identify of the compounds responsible for the mutagenic activity are unknown in these non-meat foods. Toasted grain-based foods probably contribute less than 10% of the total mutagenic activity of the diet, with meat products responsible for the reminder. The finding of varying amounts of known and unknown mutagens in some cooked foods may be responsible for the poorly understood variation in human cancer incidence worldwide.« less

METHODS FOR THE SPIRAL SALMONELLA MUTAGENICITY ASSAY INCLUDING SPECIALIZED APPLICATIONS

EPA Science Inventory

ABSTRACT

An automated approach to bacterial mutagenicity testing--the spiral Salmonella assay--was developed to simplify testing and to reduce the labor and materials required to generate dose-responsive mutagenicity information. This document provides the reader with an ...

Mutagenic activity and heterocyclic amine content of the human diet

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

Knize, M.G.; Dolbeare, F.A.; Cunningham, P.L.

1993-01-15

The mutagenic activity and the mass amount of heterocyclic amines responsible for the mutagenic activity have been measured in some cooked foods. Cooked meats are the predominant source of mutagenic activity in the diet with values ranging from 0 to 10,000 revertants per gram reported in the Ames/Salmonelia test with strain TA98. Several heterocyclic amines are present and have been quantified using solid-phase extraction followed by HPLC. Frying at higher temperatures and for longer times produces the greatest mutagenic response, and concomitantly, the largest amounts of heterocyclic amines. Most of the mutagenic activity in fried meat samples can be accountedmore » for by MelQx, DiMelQx and IQ, although other heterocylic amines are present and PHIP mutagenic activity becomes significant at higher temperatures. Non-meat products such as baked breads can also form significant mutagenic activity, particularly when overcooked. Commercially prepared hamburgers made from meat substitutes such as tofu, wheat gluten or tempeh and fried at 210{degrees}C have up to 10% of the mutagenic activity of a fried beef patty cooked under the same conditions. When detected, amounts of heterocyclic amines in fried beef patties range from a total of 0.35 ng/g for commercial beef hamburgers to 142 ng/g for a beef patty cooked over a barbecue. Dietary intake is expected to have a large range, from less than one microgram per day to over 50 micrograms per day based on current knowledge of known heterocyclic amine chemicals and heterocyclic amine-containing foods.« less

From the Cover: An Investigation of the Genotoxicity and Interference of Gold Nanoparticles in Commonly Used In Vitro Mutagenicity and Genotoxicity Assays.

PubMed

George, Jiya M; Magogotya, Millicent; Vetten, Melissa A; Buys, Antoinette V; Gulumian, Mary

2017-03-01

The suitability of 4 in vitro assays, commonly used for mutagenicity and genotoxicity assessment, was investigated in relation to treatment with 14 nm citrate-stabilized gold nanoparticles (AuNPs). Specifically, the Ames test was conducted without metabolic activation, where no mutagenic effects were observed. High resolution transmission electron microscopy and Cytoviva dark-field image analysis showed that AuNPs did not enter the bacterial cells, thus confirming the unreliability of the Ames test for nanoparticle mutagenicity studies. In addition, the Chinese hamster ovary (CHO) cell line was used for Comet, Chromosome aberration and Micronucleus assays. CHO cells were treated with AuNPs for 20 h at 37 °C. Cytotoxicity was not detected by cell impedance studies even though AuNP uptake was confirmed using Cytoviva image analysis. The DNA damage was statistically significant in treated cells when assessed by the Comet assay. However, minimal and nonstatistically significant chromosomal DNA damage was observed using the chromosome aberration and micronucleus assays. In this study, we showed that false positive results obtained with Comet assay may have been due to the possibility of direct contact between the residual, intracellular AuNPs and DNA during the assay procedure. Therefore, the chromosome aberration and micronucleus assays are better suited to assess the genotoxic effects of nanoparticles due to low probability of such direct contact occurring. Genotoxic effect of 14 and 20 nm citrate-stabilized, as well as, 14 nm PCOOH AuNPs were also investigated using chromosome aberration and micronucleus assays. Based on our acceptance criteria for a positive genotoxic response, none of the AuNPs were found to be genotoxic in either of these assays. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Mutagens in cooked foods - metabolism and genetic toxicity

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

Felton, J.S.; Bjeldanes, L.F.; Hatch, F.T.

1984-02-17

Recently developed in our laboratories is an efficient extraction procedure incorporating XAD resin adsorption which yields from 200/sup 0/C grilled ground beef an extract containing 230 Salmonella TA1538 revertants per g fresh weight of original ground beef. These mutagenic components are specific for frameshift-sensitive Salmonella strains and have an absolute requirement for metabolic activation. Normal-phase HPLC separation of methanol-extractable metabolites generated from reaction of 2-amino-3-methylimidazo (4,5-f)quinoline (IQ), a mutagenic component of broiled food with rat liver microsomes resulted in one direct-acting mutagenic peak and a second more polar peak still requiring metabolic activation. Two potent thermally-produced bacterial mutagens, 3-amino-1-methyl-5H-pyrido (4,3-b)more » indole (Trp-P-2) and IQ, were examined in mammalian cells. In excision repair-deficient CHO cells, Trp-P-2 exposure caused cytotoxicity, mutagenicity, sister chromatid exchange, and chromosomal aberrations at concentrations more than 30-fold lower than those for IQ. In normal repair-proficient CHO cells Trp-P-2 was one-half as active and IQ was inactive. Relative to Trp-P-2, IQ is much more potent in the Salmonella bacterial system than in mammalian CHO cells.« less

Computational identification of structural factors affecting the mutagenic potential of aromatic amines: study design and experimental validation.

PubMed

Slavov, Svetoslav H; Stoyanova-Slavova, Iva; Mattes, William; Beger, Richard D; Brüschweiler, Beat J

2018-07-01

A grid-based, alignment-independent 3D-SDAR (three-dimensional spectral data-activity relationship) approach based on simulated 13 C and 15 N NMR chemical shifts augmented with through-space interatomic distances was used to model the mutagenicity of 554 primary and 419 secondary aromatic amines. A robust modeling strategy supported by extensive validation including randomized training/hold-out test set pairs, validation sets, "blind" external test sets as well as experimental validation was applied to avoid over-parameterization and build Organization for Economic Cooperation and Development (OECD 2004) compliant models. Based on an experimental validation set of 23 chemicals tested in a two-strain Salmonella typhimurium Ames assay, 3D-SDAR was able to achieve performance comparable to 5-strain (Ames) predictions by Lhasa Limited's Derek and Sarah Nexus for the same set. Furthermore, mapping of the most frequently occurring bins on the primary and secondary aromatic amine structures allowed the identification of molecular features that were associated either positively or negatively with mutagenicity. Prominent structural features found to enhance the mutagenic potential included: nitrobenzene moieties, conjugated π-systems, nitrothiophene groups, and aromatic hydroxylamine moieties. 3D-SDAR was also able to capture "true" negative contributions that are particularly difficult to detect through alternative methods. These include sulphonamide, acetamide, and other functional groups, which not only lack contributions to the overall mutagenic potential, but are known to actively lower it, if present in the chemical structures of what otherwise would be potential mutagens.

Determination of mutagenicity of the precipitate formed by sodium hypochlorite and chlorhexidine using the Ames test.

PubMed

Patil, Pranali; Aminoshariae, Anita; Harding, Jarrod; Montagnese, Thomas A; Mickel, Andre

2016-04-01

The aim of this study was to determine the direct mutagenic potential of any precipitate formed by combining sodium hypochlorite (NaOCl) and chlorhexidine (CHX). The precipitates formed by NaOCl and CHX were dissolved in 100% dimethyl sulfoxide and cultured with mutant Salmonella Typhimurium strains. The cells were observed for reverse mutation. The numbers of positive/mutated wells were statistically compared with those in the background plates using the two-sample proportion independent t-test. The precipitates were not found to be significantly more mutagenic than the background plates. Within the limitations of this study, the results suggest that the precipitates formed when sodium hypochlorite and chlorhexidine contact did not show mutagenic (and are therefore carcinogenic) potential. © 2015 Australian Society of Endodontology.

The photo-oxidation of automobile emissions: measurements of the transformation products and their mutagenic activity

NASA Astrophysics Data System (ADS)

Kleindienst, Tadeusz E.; Smith, David F.; Hudgens, Edward E.; Snow, Richard F.; Perry, Erica; Claxton, Larry D.; Bufalini, Joseph J.; Black, Francis M.; Cupitt, Larry T.

Dilute mixtures of automobile emissions (comprising 50% exhaust and 50% surrogate evaporative emissions) were irradiated in a 22.7 m 3 smog chamber and tested for mutagenic activity by using a variant of the Ames test. The exhaust was taken from a single vehicle, a 1977 Ford Mustang equipped with a catalytic converter. Irradiated and nonirradiated gas-phase emissions were used in exposures of the bacteria, Salmonella typhimurium, strains TA100 and TA98. A single set of vehicular operating conditions was used to perform multiple exposures. The mutagenic activities of extracts from the particulate phase were also measured with the standard plate incorporation assay. (In most experiments only direct-acting mutagenic compounds were measured.) The gas-phase data for TA100 and TA98 showed increased activity for the irradiated emissions when compared to the nonirradiated mixture, which exhibited negligible activity with respect to the control values. The particulate phase for both the irradiated and nonirradiated mixtures showed negligible activity when results were compared to the control values for both strains. However, the experimental conditions limited the amount of extractable mass which could be collected in the particulate phase. The measured activities from the gas phase and particulate phase were converted to the number of revertants per cubic meter of effluent (i.e. the mutagenic density) to compare the contributions of each of these phases to the total mutagenic activity for each strain. Under the experimental conditions of this study, the mutagenic density of the gas-phase component of the irradiated mixture contributed approximately two orders of magnitude more of the total TA100 activity than did the particulate phase. For TA98 the gas-phase component contributed approximately one order of magnitude more. However, caution must be exercised in extrapolating these results to urban atmospheres heavily impacted by automotive emissions, because the bacterial

Bacterial and human cell mutagenicity study of some C18H10 cyclopenta-fused polycyclic aromatic hydrocarbons associated with fossil fuels combustion.

PubMed Central

Lafleur, A L; Longwell, J P; Marr, J A; Monchamp, P A; Plummer, E F; Thilly, W G; Mulder, P P; Boere, B B; Cornelisse, J; Lugtenburg, J

1993-01-01

A number of isomeric C18H10 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 C18H10 CP-PAHs: benzo[ghi]fluoranthene (BF), cyclopenta[cd]pyrene (CPP), cyclopent[hi]acephenanthrylene (CPAP), and cyclopent[hi]aceanthrylene (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 C18H10 species often found in combustion and pyrolysis samples. Chemical analysis of selected combustion and pyrolysis samples showed that CPP was generally the most abundant C18H10 isomer, followed by CPAP and BF. CPAA was detected only in pyrolysis products from pure PAHs. We tested the four C18H10 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 acephenanthyrlene. Although the mutagenicities of CPAP and acephenanthrylene are similar, the mutagenic activity of CPAA is an order of magnitude greater than that of aceanthyrlene. PMID:8354201

Azo dyes in clothing textiles can be cleaved into a series of mutagenic aromatic amines which are not regulated yet.

PubMed

Brüschweiler, Beat J; Merlot, Cédric

2017-08-01

Azo dyes represent the by far most important class of textile dyes. Their biotransformation by various skin bacteria may release aromatic amines (AAs) which might be dermally absorbed to a major extent. Certain AAs are well known to have genotoxic and/or carcinogenic properties. Correspondingly, azo dyes releasing one of the 22 known carcinogenic AAs are banned from clothing textiles in the European Union. In the present study, we investigated the mutagenicity of 397 non-regulated AAs potentially released from the 470 known textile azo dyes. We identified 36 mutagenic AAs via publicly available databases. After predicting their mutagenicity potential using the method by Bentzien, we accordingly allocated them into different priority groups. Ames tests on 18 AAs of high priority showed that 4 substances (22%) (CASRN 84-67-3, 615-47-4, 3282-99-3, 15791-87-4) are mutagenic in the strain TA98 and/or TA100 with and/or without rat S9 mix. Overall, combining the information from the Ames tests and the publicly available data, we identified 40 mutagenic AAs being potential cleavage products of approximately 180 different parent azo dyes comprising 38% of the azo dyes in our database. The outcome of this study indicates that mutagenic AAs in textile azo dyes are of much higher concern than previously expected, which entails implications on the product design and possibly on the regulation of azo dyes in the future. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

Analysis of mutagenic activity of biohazardous organics in Kanawha River sediments. Technical completion report

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

White, A.R.; Waldron, M.C.

1988-01-01

Residual chemical contamination of Kanawha River sediments may constitute a health hazard. Sediment cores have been analyzed using a coupled bioassay/chemical fractionation procedure. Both bacterial mutagenicity and sister chromatid exchange (SCE) analyses were conducted on sediment samples. Pocatalico River sediments extracts showed no response in either bacterial mutagenicity assay or SCE assay. Extracts from Armour Creek and the Kanawha River induced mutagenicities in the presence of S9 enzymes. The same extracts produced a significant increase in human chromosomal cross-over events.

Mutagenicity of nitrogen compounds from synthetic crude oils: collection, separation and biological testing

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

Rao, T K; Epler, J L; Guerin, M R

1980-01-01

In order to determine the long range health effects such as carcinogenicity/mutagenicity/teratogenicity/toxicity, associated with the newly emerging energy technologies, we have utilized the Ames Salmonella assay to evaluate mutagenic properties of synthetic fuels. Coupling with class fractionation was necessary. Organic extraction and liquid/liquid partitioning was used to separate acidic and basic fraction. The neutral material was separated using Sephadex LH-20 gel filtration into saturated and aromatic fractions of various ring sizes. The alkaline fraction was subfractionated eluting with benzene and ethanol on a basic alumina column and then with isopropanol and acetone using a Sephadex LH-20 gel column. The frameshiftmore » strain TA-98 was utilized along with Aroclor-induced rat liver homogenate (S-9 mix) for the mutagenicity assay. The natural crude oils were slightly mutagenic, the polynucleararomatics constituting the activity, while the coal-derived fuels indicated mutagenicity associated with alkaline constituents as well as polyaromatics. Hydrotreated coal (H-coal, HDT) or Shale (Paraho-Shale oil, HDT) derived fuels were not mutagenic. Ninety percent of the mutagenic activity in alkaline fraction was recovered in the acetone subfraction. High resolution spectroscopy of this fraction indicates polycyclic aromatic primary amines along with azaarenes as organic constituents responsible for the mutagenic activity associated with shale- and coal-derived fuels.« less

Mutagenicity assessment of aerosols in emissions from domestic combustion processes.

PubMed

Canha, Nuno; Lopes, Isabel; Vicente, Estela Domingos; Vicente, Ana M; Bandowe, Benjamin A Musa; Almeida, Susana Marta; Alves, Célia A

2016-06-01

Domestic biofuel combustion is one of the major sources of regional and local air pollution, mainly regarding particulate matter and organic compounds, during winter periods. Mutagenic and carcinogenic activity potentials of the ambient particulate matter have been associated with the fraction of polycyclic aromatic hydrocarbons (PAH) and their oxygenated (OPAH) and nitrogenated (NPAH) derivatives. This study aimed at assessing the mutagenicity potential of the fraction of this polycyclic aromatic compound in particles (PM10) from domestic combustion by using the Ames assays with Salmonella typhimurium TA98 and TA100. Seven biofuels, including four types of pellets and three agro-fuels (olive pit, almond shell and shell of pine nuts), were tested in an automatic pellet stove, and two types of wood (Pinus pinaster, maritime pine, and Eucalyptus globulus, eucalypt) were burned in a traditional wood stove. For this latter appliance, two combustion phases-devolatilisation and flaming/smouldering-were characterised separately. A direct-acting mutagenic effect for the devolatilisation phase of pine combustion and for both phases of eucalypt combustion was found. Almond shell revealed a weak direct-acting mutagenic effect, while one type of pellets, made of recycled wastes, and pine (devolatilisation) presented a cytotoxic effect towards strain TA100. Compared to the manually fired appliance, the automatic pellet stove promoted lower polyaromatic mutagenic emissions. For this device, only two of the studied biofuels presented a weak mutagenic or cytotoxic potential.

Identification of mutagenic transformation products generated during oxidation of 3-methyl-4-nitrophenol solutions by orbitrap tandem mass spectrometry and quantitative structure-activity relationship analyses.

PubMed

Matsushita, Taku; Honda, Shiho; Kuriyama, Taisuke; Fujita, Yuki; Kondo, Takashi; Matsui, Yoshihiko; Shirasaki, Nobutaka; Takanashi, Hirokazu; Kameya, Takashi

2018-02-01

We used Ames assays to investigate the effects of ozonation (designated O 3 ), ozonation followed by chlorination (O 3 /Cl), an advanced oxidation process (AOP, UV/H 2 O 2 ), and AOP followed by chlorination (AOP/Cl) on the mutagenicity of solutions of 3-methyl-4-nitrophenol (3M4NP), a major environmental degradation product of the organophosphorus insecticide fenitrothion. Whereas O 3 did not induce mutagenicity, O 3 /Cl, AOP, and AOP/Cl converted 3M4NP into mutagenic transformation products (TPs). Using liquid chromatography-mass spectrometry, we detected a total of 138 peaks in the solutions subjected to O 3 /Cl, AOP, and AOP/Cl. To elucidate the TPs responsible for the observed mutagenicity, we performed simple regression analyses of the relationship between the area of each peak and the observed mutagenicity of samples withdrawn periodically during each oxidation process. The area of each of 10 peaks was found to be positively correlated (r 2  ≥ 0.8) with the observed mutagenicity, suggesting that the TPs corresponding to these peaks contributed to the mutagenicity. After taking into account the consistency of mutagenicity induction by the oxidation processes and analyzing the peaks by tandem mass spectrometry, we identified 3 TPs, corresponding to 6 peaks, as candidate mutagens. These TPs were assessed by means of 4 quantitative structure-activity relationship (QSAR) models, and all 3 were predicted to be mutagenic by at least one model. This result was consistent with our assumption that these TPs were mutagens. Ames assays of an authentic sample of one of the 3 TPs revealed that it did not contribute to the mutagenicity. This left 3-methoxy-4-nitrophenol and 2-[(E)-[(2,5-dihydroxyphenyl) methylidene]amino]-5-dihydroxybenzaldehyde on the list of mutagens suspected of contributing to the mutagenicity induced by AOP. No TPs were identified as candidate mutagens responsible for the mutagenicity induced by O 3 /Cl and AOP/Cl. Copyright © 2017 Elsevier Ltd

Mutagenicity of edible palm oil on the Ghanaian market before and after repeated heating.

PubMed

Asare, George A; Okyere, Genevieve O; Asante, Matilda; Brown, Charles A; Santa, Sheila; Asiedu, Bernice

2013-12-01

Red palm oil produced in Ghana largely by village folks has never been tested for its mutagenic potential. The study aimed at determining the mutagenicity of high-energy heated red palm oil (RRPO) and refined, bleached imported palm oil (PO) on the Ghanaian market. Samples of RRPO and PO were 1× and 5× heated for 10 min at 180 °C with a cooling period of 5 h in-between. Unheated, together with heated samples, were tested for mutagenicity using Salmonella typhimurium TA 98 and TA 100 tester stains. Unheated PO was negative for the Ames mutagenicity test with TA 98 strain. However, 1× and 5× heated PO were mutagenic (P = 0.05, each). Testing PO, using TA 100 strain was negative. RRPO was mutagenic with TA 98 strain for heated oils (P = 0.05, each). Assays with TA 100 strain showed highly significant mutations (P = 0.001, each) that increased with increasing heating frequency. PO 1× and 5× heated samples caused significant frameshift mutation in the S. typhimurium TA 98 strain. RRPO caused highly significant point and frameshift mutations in heated samples. Furthermore, unheated RRPO mutagenic potential has serious health implications. © 2013 Institute of Food Technologists®

Mutagenicity studies in a tyre plant: in-vitro activity of urine concentrates and rubber chemicals.

PubMed

Crebelli, R; Falcone, E; Aquilina, G; Carere, A; Paoletti, A; Fabri, G

1984-01-01

A possible occupational contribution to urinary mutagenicity was studied in a tyre plant, by assaying concentrates of urine from 72 workmen and 23 controls for their activity in the Ames test and microtitre fluctuation test. The results show that smoking habits but not occupation are related to the appearance of a detectable urinary mutagenicity in strain TA98. A possible synergistic effect of occupation was, however, observed among tyre builders who were smokers. Mutagenicity screening of 25 rubber chemicals, of major technological relevance and used in high volume in the workplace investigated, showed that three of them are weakly active in TA98 and TA100 (tetramethylthiuram disulfide) or TA98 alone (poly-p-dinitrosobenzene and mixed diaryl-p-phenylendiamines).

Antimutagenic effects of betel leaf extract against the mutagenicity of two tobacco-specific N-nitrosamines.

PubMed

Padma, P R; Amonkar, A J; Bhide, S V

1989-03-01

Epidemiological studies have implicated chewing tobacco alone to be more hazardous than chewing tobacco with betel quid. Experimental studies have shown that betel leaf is antimutagenic against standard mutagens like benzo[a]pyrene and dimethylbenz[a]anthracene. Since the tobacco-specific N-nitrosamines (TSNA) are the only carcinogens present in unburnt forms of tobacco, including chewing tobacco, we tested the effect of an extract of betel leaf against the mutagenicity of the two important TSNA, viz., N'-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, using the Ames Salmonella/microsome assay with TA100 +S9 and the in vivo micronucleus test. In both the test systems it was observed that betel leaf extract suppressed the mutagenic effects of both the nitrosamines to a significant extent.

Use of a Salmonella microsuspension bioassay to detect the mutagenicity of munitions compounds at low concentrations.

PubMed

George, S E; Huggins-Clark, G; Brooks, L R

2001-01-25

Past production and handling of munitions has resulted in soil contamination at various military facilities. Depending on the concentrations present, these soils pose both a reactivity and toxicity hazard and the potential for groundwater contamination. Many munitions-related chemicals have been examined for mutagenicity in the Ames test, but because the metabolites may be present in low environmental concentrations, a more sensitive method is needed to elucidate the associated mutagenicity. RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine), TNT (2,4,6-trinitrotoluene), tetryl (N-methyl-N-2,4,6-tetranitroaniline), TNB (1,3,5-trinitrobenzene) and metabolites were examined for mutagenicity in a microsuspension modification of the Salmonella histidine reversion assay with and without metabolic activation. TNB and tetryl were positive in TA98 (32.5, 5.2revertants/nmole) and TA100 (7.4, 9.5revertants/nmole) without metabolic activation and were more potent than TNT (TA98, 0.3revertants/nmole; TA100, 2.4revertants/nmole). With the exception of the tetranitroazoxytoluene derivatives, TNT metabolites were less mutagenic than TNT. RDX and two metabolites were negative in both strains, however, hexahydro-1,3,5-trinitroso-1,3,5-triazine was positive in TA100 with and without S9. Microsuspension bioassay results tend to correlate well with published Ames test data, however, there are discrepancies among the published data sets and the microsuspension assay results.

[Usefulness of the fruit fly for assessment of mutagenicity of benzene, acetaldehyde and formaldehyde].

PubMed

Krogulski, A

1994-01-01

Among the contaminants of water, soil and air the number of mutagenic and carcinogenic substances is increasing. For the assessment of health risk connected with the simple and cheap methods are necessary which could detected and measure the mutagenicity of these substances. The widely used tests using prokaryotes give negative results in the tests of certain substances which are carcinogenic in mammals. In the case of benzene and acetaldehyde Ames test gives false negative results, and in the case of formaldehyde the results are equivocal. An advantage of fruit fly Drosophila melanogaster used for this purpose is that its cell structures, enzymes and metabolic processes are similar to those of mammals. For the demonstration of mutagenicity of benzene, acetaldehyde and formaldehyde the test of somatic mutation and recombination SMART was carried out in these flies. The results confirmed the usefulness of the SMART test for the demonstration of the mutagenicity of contaminants in the environment.

Comparison of Mutagenic Activities of Various Ultra-Fine Particles.

PubMed

Park, Chang Gyun; Cho, Hyun Ki; Shin, Han Jae; Park, Ki Hong; Lim, Heung Bin

2018-04-01

Air pollution is increasing, along with consumption of fossil fuels such as coal and diesel gas. Air pollutants are known to be a major cause of respiratory-related illness and death, however, there are few reports on the genotoxic characterization of diverse air pollutants in Korea. In this study, we investigated the mutagenic activity of various particles such as diesel exhaust particles (DEP), combustion of rice straw (RSC), pine stem (PSC), and coal (CC), tunnel dust (TD), and road side dust (RD). Ultra-fine particles (UFPs) were collected by the glass fiber filter pad. Then, we performed a chemical analysis to see each of the component features of each particulate matter. The mutagenicity of various UFPs was determined by the Ames test with four Salmonella typhimurium strains with or without metabolic activation. The optimal concentrations of UFPs were selected based on result of a concentration decision test. Moreover, in order to compare relative mutagenicity among UFPs, we selected and tested DEP as mutation reference. DEP, RSC, and PSC induced concentration-dependent increases in revertant colony numbers with TA98, TA100, and TA1537 strains in the absence and presence of metabolic activation. DEP showed the highest specific activity among the particulate matters. In this study, we conclude that DEP, RSC, PSC, and TD displayed varying degrees of mutagenicity, and these results suggest that the mutagenicity of these air pollutants is associated with the presence of polycyclic aromatic hydrocarbons (PAHs) in these particulate matters.

Mutagenic activity of overnight urine from healthy non-smoking subjects.

PubMed

Pavanello, Sofia; Lupi, Silvia; Pulliero, Alessandra; Gregorio, Pasquale; Saia, Bruno Onofrio; Clonfero, Erminio

2007-03-01

Urinary mutagenicity was evaluated in relation to environmental mutagen exposure (i.e., diet, indoor/outdoor activities, residential area etc.) on the day prior to sample collection, and also considering factors that contribute to the variability of Salmonella mutagenicity assay results. Overnight urine samples from 283 healthy non-smoking residents of northeast Italy (46% males, 20-62 years) were analyzed for mutagenicity on sensitive Salmonella typhimurium strain YG1024 with S9 mix employing the preincubation version of the plate incorporation assay (i.e., the Salmonella reverse mutation test). Urinary mutagenicity varied between 0.02 and 9.84 rev/ equiv. ml, and 7% of samples were positive (i.e., sample elicited a two-fold increase in revertants). There was an evident increase in mutagenicity in subjects with increased intake of mutagen-rich meals (n = 80) (P < 0.01 and positive urine 13% vs. 5%, P = 0.025). Indoor-exposed subjects (n = 65) also showed a higher percentage of positive urine (14% vs. 5%, P = 0.015). In particular, those subjects exposed to cooking fumes the previous evening (n = 28) revealed higher urinary mutagenicity (P = 0.035, positive urine 25% vs. 5%, P < 0.001) than non-indoor exposed. The sources of variability of the mutagenicity assay, mainly the histidine content of the urine concentrate (z = 4.06, P < 0.0001), and to a lesser extent bacterial inoculum size (z = 2.33, P = 0.019), also significantly influenced urinary mutagenicity values. In a linear multiple regression analysis, their effects were still significant (i.e., histidine content P = 0.026 and inoculum size P = 0.021), but the effects of diet, indoor exposure, and other environmental exposures (i.e., traffic and heating system exhausts, residential area) were not. It is concluded that the previous day's exposure to mutagen-rich meals and cooking fumes may influence the presence of mutagenic activity in the overnight urine of non-smoking subjects. This mutagenic activity, which

Mutagenicity of particle emissions from solid fuel cookstoves: A literature review and research perspective.

PubMed

Shen, Guofeng

2017-07-01

Household solid fuel use is a major source of many air pollutants causing severe air pollution and adverse health outcomes. In evaluation of health impacts of household air pollution, it is essential to characterize toxic properties like mutagenicity of residential fuel combustion emissions and exposure assessments. Mutagenicity of emissions from solid fuel cookstoves were analyzed through a literature review. T98 and TA100 strains are two most widely used strains in mutagenic Ames test, and results for these two strains are generally positively correlated though they have different endpoints. Direct and indirect mutagenic activities are positively correlated, and statistically insignificantly different though indirect mutagenic emissions are apparently higher. Mutagenicity emission factors on the basis of fuel energy (MJ) or useful energy delivered (MJd) for solid fuel cookstoves vary in nearly 3 orders of magnitude, ranging from 3.0×10 4 rev./MJd to 1.8×10 7 rev./MJd (or 1.1×10 4 rev./MJ to 4.2×10 6 rev./MJ). Low mutagenic emissions are reported for high efficiency stoves such as a forced-draft one. Mutagenicity emission factors are positively correlated with emissions of PM 2.5 . Relationship between mutagenicity and polycyclic aromatic hydrocarbons (PAHs) emissions is inconsistent among studies as PAHs are minor fractions of toxic organics contributing to the total mutagenicity. Generally, studies on mutagenicity of emissions from household cookstoves are very limited, and future studies are encouraged on mutagenic emissions from different fuel types and household stoves, evaluation of mutagenic activities of both gaseous and particulate emissions, and toxicology and exposure assessments of household air pollution. Copyright © 2017 Elsevier Inc. All rights reserved.

Mutagenicity and genotoxicity studies of aspartame.

PubMed

Otabe, Akira; Ohta, Fumio; Takumi, Asuka; Lynch, Barry

2018-02-08

Two studies were conducted to further assess its mutagenic and genotoxic potential. In a bacterial reverse mutation pre-incubation study, Salmonella typhimurium strains TA100, TA1535, TA98, and TA1537 and Escherichia coli WP2 uvrA were treated with aspartame at concentrations of up to 5000 μg/plate with or without metabolic activation and showed no mutagenic potential. Similarly, in vivo micronucleus testing of aspartame following gavage administration (500-2000 mg/kg body weight) to Crlj:CD1(ICR) strain SPF male mice showed no increase in the proportion of micronucleated polychromatic erythrocytes in bone marrow cells collected and evaluated 24 or 48 h post administration. Overall, aspartame had no potential for mutagenic or genotoxic activity. Copyright © 2018 Elsevier Inc. All rights reserved.

Dietary Exposure of Nigerians to Mutagens and Estrogen-Like Chemicals

PubMed Central

Omoruyi, Iyekhoetin Matthew; Ahamioje, Derek; Pohjanvirta, Raimo

2014-01-01

Food and drinking water are poorly delineated sources of human exposure to chemical food mutagens and endocrine-disrupting chemicals. In this study, we investigated the presence of mutagens and chemicals exhibiting estrogenic activity in the daily diet of Nigerians, using in vitro assays. Commercially processed foods or snacks and various brands of pure water sachets were extracted by solid-phase extraction and liquid-liquid extraction, respectively. Mutagenicity was determined by the conventional Ames test and two complementary assays on two strains of Salmonella (TA 100 and TA 98), while the estrogenic activity was assessed by a yeast bioluminescent assay, using two recombinant yeast strains (Saccharomyces cerevisiae BMAEREluc/ERα and S. cerevisiae BMA64/luc). A third of the food varieties investigated (chin-chin, hamburger, suya and bean cake) were mutagenic in all three assays, either in the presence or absence of S9 mix. Of the packed water samples, five out of the sixteen investigated (31%), were found to be estrogenic, with estradiol and bisphenol A equivalents ranging from 0.79 to 44.0 ng/L and 124.2 to 1,000.8 ng/L, respectively. Hence, although the current situation in Nigeria does not appear to be substantially worse than, e.g., in Europe, regular monitoring is warranted in the future. PMID:25153465

The effects of pre-incubation period and norharman on the mutagenic potency of 4-dimethylaminoazobenzene and 3'-methyl-4-dimethylaminoazobenzene in S. typhimurium.

PubMed

Lefevre, P A; Ashby, J

1981-01-01

The effects of the co-mutagen norharman on the mutagenicity of the rodent liver carcinogens 4-dimethyl-aminoazobenzene (DAB) and 3'-methyl-4-dimethyl-aminoazobenzene (3'-MeDAB) have been evaluated using the Ames Salmonella mutation assay. A period of pre-incubation was found to be necessary in order to detect DAB as a mutagen and to increase the initially weak response observed for 3'MeDAB; maximum responses were seen after 1 h pre-incubation in each case. The co-mutagenic properties of norharman were at their maximum for both azo-dyes in the direct plate-incorporation assay. Pre-incubation of either compound with norharman for increasing periods of time resulted in a decrease in potentiation, until after 1 h, an inhibition of mutagenicity was observed.

Modulatory effects of Cassia fistula fruits against free radicals and genotoxicity of mutagens.

PubMed

Kaur, Sandeep; Kumar, Manish; Kaur, Paramjeet; Kaur, Varinder; Kaur, Satwinderjeet

2016-12-01

Cassia fistula L. (Fabaceae) fruits are highly recommended in folklore medicine for curing various ailments. In the current study, methanol (CaFM), hexane (CaFH), chloroform (CaFCl), ethyl acetate (CaFE), butanol (CaFB) and aqueous (CaFA) fractions of C. fistula fruits were investigated for their potential to inhibit the genotoxicity of mutagens and free radicals. The antimutagenicity of fractions was evaluated against the reactive carcinogenic ester generating mutagen, 2-aminofluorene (2-AF) and frame-shift mutation inducing mutagen, 4-nitro-o-phenylenediamine (NPD) in Ames Salmonella typhimurium TA98 tester strain. Among the fractions, CaFE showed strongest protective effect against the mutagenicity of both S9-dependent and direct-acting mutagen with an inhibitory percentage of 81% and 64% at the concentration of 1 × 10 3 and 2.5 × 10 3 respectively. All the fractions were analyzed for free radical scavenging activity using DPPH, nitric oxide, lipid peroxidation and superoxide anion assays. CaFE fraction showed maximum antioxidant activity in comparison to other fractions with an IC 50 of 97.01, 172.36, 144 and 264.79 μg/ml respectively. High performance liquid chromatography showed the presence of catechin, epicatechin and umbelliferone in appreciable amount which may account for its efficacy in combating free radicals and also showed protective effect against the mutagenicity of S9-dependent mutagen, 2-AF. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

Dugan, A M; Tkacheva, D L

2011-01-01

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

Screening complex hazardous wastes for mutagenic activity using a modified version of the TLC/Salmonella assay.

PubMed

Houk, V S; Claxton, L D

1986-03-01

10 complex hazardous wastes were tested for mutagenic activity using a modified version of the TLC/Salmonella assay developed by Bjørseth et al. (1982). This fractionation/bioassay scheme couples thin-layer chromatography (TLC) with the Salmonella/mammalian-microsome (Ames) assay for the detection of mutagenic constituents in complex mixtures. Crude (unadulterated) hazardous wastes and selected hazardous waste extracts were fractionated on commercially available cellulose TLC plates. Mutagenicity testing was performed in situ by applying a single overlay of minimal growth agar, tester strain TA98 or TA100, and the optional metabolic activation system directly onto the developed chromatogram. A mutagenic effect was indicated either by the appearance of localized clusters of revertant colonies or by an increase in total revertant growth vis-à-vis control plates. 7 of 10 hazardous wastes (including tars, emulsions, sludges, and spent acids and caustics) demonstrated mutagenic activity when tested by this method. To assess the sensitivity of the modified TLC/Salmonella assay, 14 Salmonella mutagens from a wide range of chemical classes and polarities were tested. Selected compounds included heterocyclics, aromatic amines, alkylating agents, antitumor agents, a nitrosamine and a nitroaromatic. 11 of the 14 mutagens were positive in this test system. The 3 compounds refractory to analysis included a polycyclic aromatic hydrocarbon and two volatiles.

Physical factors affecting the mutagenicity of fly ash from a coal-fired power plant.

PubMed

Fisher, G L; Chrisp, C E; Raabe, O G

1979-05-25

The two finest, most respirable coal fly ash fractions collected from the smokestack of a power plant were more mutagenic than two coarser fractions. Mutagenicity was evaluated in the histidine-requiring bacterial strains TA 1538, TA 98, and TA 100 of Salmonella typhimurium. Ash samples collected from the hoppers of an electrostatic precipitator in the plant were not mutagenic. The mutagens in coal fly ash were resistant to x-ray or ultraviolet irradiation, possibly as a result of stabilization by fly ash surfaces. All mutagenic activity is lost with heating to 350 degrees C.

Evaluation of micronuclei induction capacity and mutagenicity of organochlorine and organophosphate pesticides.

PubMed

Yaduvanshi, Santosh K; Srivastava, Nalini; Marotta, Francesco; Jain, Shalini; Yadav, Hariom

2012-09-01

The genotoxic and mutagenic effects of two commonly used organochlorine pesticides, lindane (LND) and endosulfan (ENS), and two commonly used organophosphate pesticides, chlorpyrifos (CPF) and monocrotophos (MCP) were assessed using in vivo mouse bone marrow micronucleus test and in vitro Ames Salmonella/ microsome mutagenicity test. The results showed that these pesticides alone or in combination, induced significantly high frequency of micronuclei (MN) formation that increased with concentration of pesticides. All these four pesticides produced significant increase in the frequencies of micronucleated-polychromatic erythrocytes (MN-PCE) and decrease infrequencies of PCE in dose-dependent manner. The results indicate the suppression of proliferative activity of the bone marrow and increase in the extent of cell death. ENS and MCP showed mutagenic potential in Salmonella/ microsome assay. ENS induced mutagenic and nontoxic response only in TA98 tester strain of S.typhimurium at the dose of 500 μg/plate and in the absence of metabolic activation. MCP showed weak mutagenic and nontoxic effect only in TA100 tester strain at the dose of 5000 μg/plate in both assays, with or without metabolic activation when compared with negative control. MCP was toxic in TA98 tester strain at the dose of 5000 μg/plate in absence of metabolic activation while reduction in toxicity was seen on addition of S9 mixture. The study clearly showed the genotoxic potential of all these four pesticides and mutagenic response of endosulfan and monocrotophos.

Mutagenicity of arsenic in mammalian cells: role of reactive oxygen species

NASA Technical Reports Server (NTRS)

Hei, T. K.; Liu, S. X.; Waldren, C.

1998-01-01

Arsenite, the trivalent form of arsenic present in the environment, is a known human carcinogen that lacked mutagenic activity in bacterial and standard mammalian cell mutation assays. We show herein that when evaluated in an assay (AL cell assay), in which both intragenic and multilocus mutations are detectable, that arsenite is in fact a strong dose-dependent mutagen and that it induces mostly large deletion mutations. Cotreatment of cells with the oxygen radical scavenger dimethyl sulfoxide significantly reduces the mutagenicity of arsenite. Thus, the carcinogenicity of arsenite can be explained at least in part by it being a mutagen that depends on reactive oxygen species for its activity.

Characterization and validation of an in silico toxicology model to predict the mutagenic potential of drug impurities*

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

Valerio, Luis G., E-mail: luis.valerio@fda.hhs.gov; Cross, Kevin P.

Control and minimization of human exposure to potential genotoxic impurities found in drug substances and products is an important part of preclinical safety assessments of new drug products. The FDA's 2008 draft guidance on genotoxic and carcinogenic impurities in drug substances and products allows use of computational quantitative structure–activity relationships (QSAR) to identify structural alerts for known and expected impurities present at levels below qualified thresholds. This study provides the information necessary to establish the practical use of a new in silico toxicology model for predicting Salmonella t. mutagenicity (Ames assay outcome) of drug impurities and other chemicals. We describemore » the model's chemical content and toxicity fingerprint in terms of compound space, molecular and structural toxicophores, and have rigorously tested its predictive power using both cross-validation and external validation experiments, as well as case studies. Consistent with desired regulatory use, the model performs with high sensitivity (81%) and high negative predictivity (81%) based on external validation with 2368 compounds foreign to the model and having known mutagenicity. A database of drug impurities was created from proprietary FDA submissions and the public literature which found significant overlap between the structural features of drug impurities and training set chemicals in the QSAR model. Overall, the model's predictive performance was found to be acceptable for screening drug impurities for Salmonella mutagenicity. -- Highlights: ► We characterize a new in silico model to predict mutagenicity of drug impurities. ► The model predicts Salmonella mutagenicity and will be useful for safety assessment. ► We examine toxicity fingerprints and toxicophores of this Ames assay model. ► We compare these attributes to those found in drug impurities known to FDA/CDER. ► We validate the model and find it has a desired predictive performance.« less

Estimation of the contribution of ultrafine particles to lung deposition of particle-bound mutagens in the atmosphere.

PubMed

Kawanaka, Youhei; Matsumoto, Emiko; Sakamoto, Kazuhiko; Yun, Sun-Ja

2011-02-15

The present study was performed to estimate the contributions of fine and ultrafine particles to the lung deposition of particle-bound mutagens in the atmosphere. This is the first estimation of the respiratory deposition of atmospheric particle-bound mutagens. Direct and S9-mediated mutagenicity of size-fractionated particulate matter (PM) collected at roadside and suburban sites was determined by the Ames test using Salmonella typhimurium strain TA98. Regional deposition efficiencies in the human respiratory tract of direct and S9-mediated mutagens in each size fraction were calculated using the LUDEP computer-based model. The model calculations showed that about 95% of the lung deposition of inhaled mutagens is caused by fine particles for both roadside and suburban atmospheres. Importantly, ultrafine particles were shown to contribute to the deposition of mutagens in the alveolar region of the lung by as much as 29% (+S9) and 26% (-S9) for the roadside atmosphere and 11% (+S9) and 13% (-S9) for the suburban atmosphere, although ultrafine particles contribute very little to the PM mass concentration. These results indicated that ultrafine particles play an important role as carriers of mutagens into the lung. Copyright © 2010 Elsevier B.V. All rights reserved.

Effects of human placental S9 and induced rat liver S9 on the mutagenicity of drinking waters processed from humus-rich surface waters

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

Vartiainen, T.; Lampelo, S.

The mutagenicity of chlorinated drinking waters processed from humus-rich surface waters has been shown to be very high. The effect of placental S9 on the mutagenicity of drinking waters has not been studied previously. The purpose of this study was to compare the effects of human placental and rat liver microsomal fractions on the mutagenicity of drinking waters processed from humus-rich surface waters. The samples of 34 drinking and two raw waters from 26 localities in Finland were tested for mutagenicity in Ames Salmonella typhimurium tester strain TA100 with and without metabolic activations. Between the drinking water samples, clear differencesmore » were recorded in the presence of placental and rat liver S9, suggesting different mutagens in the drinking waters. Rat liver S9 decreased the mutagenicities of drinking water concentrates, but placental S9 increased, decreased, or had no effect. It is not known if placental mutagenicity enhancing system might cause any health hazard to a developing fetus.« less

Mutagenicity of commercial hair dyes and detection of 2,7-diaminophenazine.

PubMed

Watanabe, T; Hirayama, T; Fukui, S

1990-08-01

Four commercial oxidative-type hair dye formulations, A, B, C, and D, were treated with hydrogen peroxide (H2O2) to simulate normal conditions of use, and the oxidized hair dyes were tested for their mutagenicity in Salmonella typhimurium TA98 in the presence of a mammalian metabolic activation system (S9 mix). Most of them did not show obvious mutagenicity in the range of 1-25 microliters/plate and all exhibited bactericidal activity at 10 microliters/plate. In order to evaluate the mutagenicity of hair dyes both before and after H2O2 oxidation, rayon linked to a copper-phthalocyanine derivative (blue rayon) was used as an adsorbent for the elimination of interfering bactericidal compounds. Adsorbed compounds on blue rayon were eluted with ammoniacal methanol and eluents were subjected to the Ames test. The mutagenicity of the blue-rayon extracts in TA98 with S9 mix was increased by H2O2 oxidation. The blue-rayon extracts obtained from oxidized A and B were potent mutagens and reverted 334 and 999 colonies/10 microliters of original substance, respectively. In addition, 88 and 249 ng of 2,7-diaminophenazine, which was extremely mutagenic in TA98 with S9 mix, were detected in the extracts of 40 ml of the hair dye formulations A and B, respectively. The mutagenicity in oxidized hair dye formulations was successfully detected by use of blue-rayon extraction. 2,7-Diaminophenazine was only formed in the hair dye formulations containing m-phenylenediamine by H2O2 oxidation. Therefore, attention needs to be paid to the use of m-phenylenediamine as a hair dye component, not only for its own toxicity but also for that of its oxidation products.

Application of effect-directed analysis to identify mutagenic nitrogenous disinfection by-products of advanced oxidation drinking water treatment.

PubMed

Vughs, D; Baken, K A; Kolkman, A; Martijn, A J; de Voogt, P

2018-02-01

Advanced oxidation processes are important barriers for organic micropollutants in (drinking) water treatment. It is however known that medium pressure UV/H 2 O 2 treatment may lead to mutagenicity in the Ames test, which is no longer present after granulated activated carbon (GAC) filtration. Many nitrogen-containing disinfection by-products (N-DBPs) result from the reaction of photolysis products of nitrate with (photolysis products of) natural organic material (NOM) during medium pressure UV treatment of water. Identification of the N-DBPs and the application of effect-directed analysis to combine chemical screening results with biological activity would provide more insight into the relation of specific N-DBPs with the observed mutagenicity and was the subject of this study. To this end, fractions of medium pressure UV-treated and untreated water extracts were prepared using preparative HPLC and tested using the Ames fluctuation test. In addition, high-resolution mass spectrometry was performed on all fractions to assess the presence of N-DBPs. Based on toxicity data and read across analysis, we could identify five N-DBPs that are potentially genotoxic and were present in relatively high concentrations in the fractions in which mutagenicity was observed. The results of this study offer opportunities to further evaluate the identity and potential health concern of N-DBPs formed during advanced oxidation UV drinking water treatment.

Temporal and spatial distribution of particulate carcinogens and mutagens in Bangkok, Thailand.

PubMed

Pongpiachan, Siwatt; Choochuay, C; Hattayanone, M; Kositanont, C

2013-01-01

To investigate the level of genotoxicity over Bangkok atmosphere, PM10 samples were collected at the Klongchan Housing Authority (KHA), Nonsree High School (NHS), Watsing High School (WHS), Electricity Generating Authority of Thailand (EGAT), Chokchai 4 Police Station (CPS), Dindaeng Housing Authority (DHA) and Badindecha High School (BHS). For all monitoring stations, each sample covered a period of 24 hours taken at a normal weekday every month from January-December 2006 forming a database of 84 individual air samples (i.e. 12?7=84). Atmospheric concentrations of low molecular weight PAHs (i.e. phenanthrene, anthracene, pyrene and fluoranthene) were measured in PM10 at seven observatory sites operated by the pollution control department of Thailand (PCD). The mutagenicity of extracts of the samples was compared in Salmonella according to standard Ames test method. The dependence of the effects on sampling time and on sampling location was investigated with the aid of a calculation of mutagenic index (MI). This MI was used to estimate the increase in mutagenicity above background levels (i.e. negative control) at the seven monitoring sites in urban area of Bangkok due to anthropogenic emissions within that area. Applications of the AMES method showed that the average MI of PM10 collected at all sampling sites were 1.37±0.10 (TA98; +S9), 1.24±0.08 (TA98; -S9), 1.45±0.10 (TA100; +S9) and 1.30±0.09 (TA100; -S9) with relatively less variations. Analytical results reconfirm that the particulate PAH concentrations measured at PCD air quality monitoring stations are moderately low in comparison with previous results observed in other countries. In addition, the concept of incremental lifetime particulate matter exposure (ILPE) was employed to investigate the potential risks of exposure to particulate PAHs in Bangkok atmosphere.

Ames Mutagenicity Test of the RDX Replacement, Triaminoguanidinium-1-methyl-5-nitriminotetrazolate (TAG-MNT)

DTIC Science & Technology

2010-03-01

5-nitriminotetrazolate (TAG-MNT) using the Xenometrix Microplate Format Mutagenicity Assay with five strains of bacteria in compliance with the...798.5265.), The U.S. Food and Drug Administration (USFDA) and OCED (OECD, 1997). f. Xenometrix has developed a proprietary microplate format (MPFTM...8217-Azotetrazolate Salts. Chem. Mater. 17(14): 3784-3793. Kasuske, L., J. M. Schofer and K. Hasegawa. 2009. Two marines with generalized seizure activity. J Emerg

Mutagenicity and Nitropyrene Concentration of Indoor Air Particulates Exhausted from a Kerosene Heater*1

PubMed Central

Kinouchi, Takemi; Nishifuji, Keiko; Tsutsui, Hideshi; Hoare, Sadako Louise

1988-01-01

The particulates in a room warmed with a radiant kerosene heater were collected, extracted and fractionated into diethyl ether‐soluble neutral, acidic and basic fractions. The mutagenicity of these fractions was measured with Salmonella typhimurium strains TA98, TA98NR, TA98/1,8‐DNP6 and TA100 in the presence and ahsence of S9 mix. Room air without the heater showed very low mutagenicity. However, a sample from a room at the beginning of the burning period showed very high mutagenicity (237 His+ revertants/plate/m*3 of air in strain TA98 in the absence of S9 mix). In contrast, emissions from the heater after it was burning stably showed low mutagenicity (9 His+ revertants/plate/m*3). The crude extract of particulates from the heater at the beginning of the burning period was analyzed by high‐pressure liquid chromatography (HPLC) and showed a considerable amount of nitropyrenes (NPs); the concentrations of 1‐NP and 1,6‐diNP were 1.62 ng and 0.149 ng/m*3 of air, respectively, and accounted for 1.2% and 17.6%, respectively, of the mutagenicity in strain TA98 in the absence of S9 mix. In addition, an HPLC‐Ames histogram showed that peaks of mutagenicity corresponding to 1‐NP and diNPs accounted for 75.7% (1‐NP, 4.9%; 1,6‐diNP, 17.1%; 1,8‐diNP, 46.3%; 1,3‐diNP, 7.4%) of the HPLC‐recovered mutagenicity for strain TA98 without S9 mix. These results suggest that kerosene heaters, especially immediately after ignition, create mutagenic substances such as NPs. PMID:3128503

Plant composition, pharmacological properties and mutagenic evaluation of a commercial Zulu herbal mixture: Imbiza ephuzwato.

PubMed

Ndhlala, A R; Finnie, J F; Van Staden, J

2011-01-27

Imbiza ephuzwato is a traditional herbal tonic made from a mixture of extracts of roots, bulbs, rhizomes and leaves of 21 medicinal plants and is used in traditional medicine as a multipurpose remedy. To compile and investigate the bioactivity and mutagenic effects of extracts of the 21 plant species used in the preparation of Imbiza ephuzwato herbal tonic. The 21 plant species used to make Imbiza ephuzwato herbal mixture were each investigated for their pharmacological properties. Petroleum ether (PE), dichloromethane (DCM), 80% ethanol (EtOH) and water extracts of the 21 plants were evaluated against two gram-positive, two gram-negative bacteria and a fungus Candida albicans. The extracts were also evaluated for their inhibitory effects against cyclooxygenase (COX-1 and -2) and acetylcholinesterase AChE enzymes. Mutagenic effects of the water extracts were evaluated using the Ames test. Gunnera perpensa and Rubia cordifolia were the only plant species used to manufacture Imbiza ephuzwato that had water extracts which showed good antibacterial activity. The extracts of G. perpensa (EtOH), Hypericum aethiopicum (DCM) and Urginea physodes (EtOH) showed the best antifungal activity. The water extracts of H. aethiopicum, G. perpensa, Drimia robusta, Vitellariopsis marginata, Scadoxus puniceus and Momordica balsamina showed percentage inhibition of COX-1 that was over 70%. For COX-2 enzyme, the water extracts of G. perpensa, Cyrtanthus obliquus, M. balsamina and Tetradenia riparia exhibited inhibitory activity above 70%. Water extracts of G. perpensa, C. obliquus, V. marginata, Asclepias fruticosa and Watsonia densiflora showed good AChE inhibitory activity (>80%). The Ames test results revealed that all the water extracts of the 21 plant species used to make Imbiza ephuzwato were non-mutagenic towards the Salmonella typhimurium TA98 strain for the assay with and without S9 metabolic activation. In contrast, Imbiza ephuzwato showed mutagenic effects after exposure to S

Ethanol- or acetone-pretreatment of mice strongly enhances the bacterial mutagenicity of dimethylnitrosamine in assays mediated by liver subcellular fraction, but not in host-mediated assays.

PubMed

Glatt, H; de Balle, L; Oesch, F

1981-01-01

The activation of dimethylnitrosamine (DMN) to a bacterial mutagen in liver subcellular fraction and in intrasanguinous host-mediated assays was studied, in particular the effect of pretreatment of the animals with ethanol or acetone. Salmonella typhimurium TA 92 was much more sensitive to DMN mutagenicity than TA 100 and TA 1535 or Escherichia coli WP2uvrA and was used for the main part of the study. Noteworthy, in part already known, features of the in vitro activation are the relatively low pH optimum (pH 6-6.4), the non-linear dose-mutagenic response-relationship and the relatively high doses of DMN required for activation with control preparations. Pretreatment of mice with ethanol or acetone greatly reduced the minimal mutagenically effective concentration of DMN in the in vitro assay. Pretreatment with Aroclor 1254, an inducer frequently used in mutagenicity research, showed little effect when used alone, but reduced the potentiation by acetone. The results of the host-mediated assays substantially differed from those of the in vitro activation assays (a) in the relatively low dose of DMN required for mutagenicity to occur and (b) in the lack of potentiation by acetone-or ethanol-pretreatment. Acetone even led to a marginal decrease in mutagenicity. As a possible explantation for this apparent discrepancy were assume that with the in vitro system the activity of the dilute metabolizing system is limiting for the activation of DMN and induction therefore will increase the mutagenicity, whereas in vivo DMN is quantitatively metabolized in both induced and non-induced animals. The results show that caution has to be taken in the interpretation from in vitro results to the in vivo situation. In particular our in vivo experiments do not support the hypothesis that the induction by ethanol of an activating system with a low Km (which would strongly activate traces of DMN ingested with many foods) is one of the reasons for the increased risk of liver tumors in

Influence of ozonation on the in vitro mutagenic and toxic potential of secondary effluents.

PubMed

Petala, M; Samaras, P; Zouboulis, A; Kungolos, A; Sakellaropoulos, G P

2008-12-01

Reclamation of municipal effluents by advanced treatment processes is an attractive perspective for facing certain water shortage problems. However, the application of tertiary techniques should be thoroughly examined for their potential hazardous effects. Ozonation is an efficient chemical oxidation method, often used in wastewater reclamation, which may result in by-products that may alter the toxic and mutagenic properties of effluents. In this study, Ames test and Microtox test were used for the evaluation of ozonation efficiency to upgrade secondary effluents quality. In general, the toxic response and mutagenic effect without metabolic activation of test species were influenced mainly by the ozone dose and ozonation duration, whereas the mutagenic effect with metabolic activation was influenced mainly by ozone dose, indicating that ozone conditions strongly affect the formation of by-products. In most cases, the toxicity was increased and reached up to 100% (in relation to that of secondary effluent) after ozonation with 8.0 mg O3/L for 5 min. On the contrary, in most cases the mutagenic activity towards strain TA98 without metabolic activation was reduced, when ozone dose and contact time increased. However, the mutagenicity was also increased after ozonation at low ozone doses and for contact times less than 5 min. The mutagenic activity of treated effluents towards strain TA98 with metabolic activation remained about the same or was reduced, compared to that of secondary effluent, and was even eliminated after ozonation with 8.0 mg O3/L for contact times higher than 5 min.

Alphatic 3,4-epoxyalcohols. Metabolism by epoxide hydrase and mutagenic activity.

PubMed

Ortiz de Montellano, P R; Boparai, A S

1978-12-18

Rabbit hepatic microsomal epoxide hydrase catalyzes the rapid hydrolysis of 1,2-epoxy-4-heptanol to 1,2,4-heptanetriol. Both diastereomers of the substrate are hydrolyzed, and both product diastereomers are formed. Similarly both cis- and trans-3,4-epoxy-1-hexanol are hydrolyzed, albeit more slowly, to give 1,3,4-hexanetriol. The trans isomer gives exclusively one diastereomer (erythro) of the triol, while the cis isomer gives the other diastereomer (threo). The product expected if a primary cationic intermediate were to be formed and trapped intramolecularly during the hydrolysis of 1,2-epoxy-4-heptanol, 2-propyl-4-tetrahydrofuranol, was not observed. A comparison of the mutagenic activity in the Ames test of 1-heptane, 1-hepten-4-ol, 1,2-epoxyheptane, and 1,2-epoxy-4-heptanol revealed that only the latter is a detectable mutagen. A vicinal hydroxyl therefore does not interfere significantly with enzymatic epoxide hydrolysis, but it does enhance the bioalkylating potential of even an aliphatic epoxide.

Genotoxicity of air borne particulates assessed by comet and the Salmonella mutagenicity test in Jeddah, Saudi Arabia.

PubMed

Elassouli, Sufian M; Alqahtani, Mohamed H; Milaat, Waleed

2007-09-01

Fine airborne respirable particulates less than 10 micrometer (PM10) are considered one of the top environmental public health concerns, since they contain polycyclic aromatic hydrocarbons (PAHs) which are among the major carcinogenic compounds found in urban air. The objective of this study is to assess the genotoxicity of the ambient PM10 collected at 11 urban sites in Jeddah, Saudi Arabia. The PM10 extractable organic matter (EOM) was examined for its genotoxicity by the single cell gel electrophoresis (SCGE) comet assay and the Salmonella mutagenicity (Ames) test .Gas chromatography-mass spectrometry was used to quantify 16 PAH compounds in four sites. Samples from oil refinery and heavy diesel vehicles traffic sites showed significant DNA damage causing comet in 20-44% of the cells with tail moments ranging from 0.5-2.0 compared to samples from petrol driven cars and residential area, with comet in less than 2% of the cells and tail moments of < 0.02. In the Ames test, polluted sites showed indirect mutagenic response and caused 20-56 rev/ m3, mean while residential and reference sites caused 2-15 rev /m3. The genotoxicity of the EOM in both tests directly correlated with the amount of organic particulate and the PAHs concentrations in the air samples. The PAHs concentrations ranged between 0.83 ng/m3 in industrial and heavy diesel vehicles traffic sites to 0.18 ng /m3 in the residential area. Benzo(ghi)pyrene was the major PAH components and at one site it represented 65.4 % of the total PAHs. Samples of the oil refinery site were more genotoxic in the SCGE assay than samples from the heavy diesel vehicles traffic site, despite the fact that both sites contain almost similar amount of PAHs. The opposite was true for the mutagenicity in the Ames test. This could be due to the nature of the EOM in both sites. These findings confirm the genotoxic potency of the PM10 organic extracts to which urban populations are exposed.

Fecalase: a model for activation of dietary glycosides to mutagens by intestinal flora

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

Tamura, G.; Gold, C.; Ferro-Luzzi, A.

1980-08-01

Many substances in the plant kingdom and in man's diet occur as glycosides. Recent studies have indicated that many glycosides that are not mutagenic in tests such as the Salmonella test become mutagenic upon hydrolysis of the glycosidic linkages. The Salmonella test utilizes a liver homogenate to approximate mammalian metabolism but does not provide a source of the enzymes present in intestinal bacterial flora that hydrolyze the wide variety of glycosides present in nature. We describe a stable cell-free extract of human feces, fecalase, which is shown to contain various glycosidases that allow the in vitro activation of many naturalmore » glycosides to mutagens in the Salmonella/liver homogenate test. Many beverages, such as red wine (but apparently not white wine) and tea, contain glycosides of the mutagen quercetin. Red wine, red grape juice, and teas were mutagenic in the test when fecalase was added, and red wine contained considerable direct mutagenic activity in the absence of fecalase. The implications of quercetin mutagenicity and carcinogenicity are discussed.« less

QSAR modeling for predicting mutagenic toxicity of diverse chemicals for regulatory purposes.

PubMed

Basant, Nikita; Gupta, Shikha

2017-06-01

The safety assessment process of chemicals requires information on their mutagenic potential. The experimental determination of mutagenicity of a large number of chemicals is tedious and time and cost intensive, thus compelling for alternative methods. We have established local and global QSAR models for discriminating low and high mutagenic compounds and predicting their mutagenic activity in a quantitative manner in Salmonella typhimurium (TA) bacterial strains (TA98 and TA100). The decision treeboost (DTB)-based classification QSAR models discriminated among two categories with accuracies of >96% and the regression QSAR models precisely predicted the mutagenic activity of diverse chemicals yielding high correlations (R 2 ) between the experimental and model-predicted values in the respective training (>0.96) and test (>0.94) sets. The test set root mean squared error (RMSE) and mean absolute error (MAE) values emphasized the usefulness of the developed models for predicting new compounds. Relevant structural features of diverse chemicals that were responsible and influence the mutagenic activity were identified. The applicability domains of the developed models were defined. The developed models can be used as tools for screening new chemicals for their mutagenicity assessment for regulatory purpose.

In vitro mutagenicity assessment of aluminium oxide nanomaterials using the Salmonella/microsome assay.

PubMed

Balasubramanyam, A; Sailaja, N; Mahboob, M; Rahman, M F; Hussain, Saber M; Grover, Paramjit

2010-09-01

The aim of the current study was to evaluate the potential mutagenicity of aluminium oxide nanomaterials (NMs) (Al(2)O(3)-30 nm and Al(2)O(3)-40 nm). Characterization of the NMs was done before the initiation of the study. The mutagenicity of the NMs was studied by the Ames test with Salmonella typhimurium TA100, TA1535, TA98, TA97a and TA102 strains, in the presence and absence of the S9 mixture. Based on a preliminary cytotoxicity study conducted on the strains, different concentrations of Al(2)O(3)-30 nm, Al(2)O(3)-40 nm and Al(2)O(3)-bulk were selected. At all the concentrations tested, Al(2)O(3)-30 nm and Al(2)O(3)-40 nm did not significantly increase the number of revertant colonies compared to the Al(2)O(3)-bulk and control with or without S9 mixture. Our findings suggest that Al(2)O(3) NMs were devoid of any size and concentration dependent mutagenicity compared to the Al(2)O(3)-bulk and control. Copyright 2010 Elsevier Ltd. All rights reserved.

Urinary excretion of mutagens in coke oven workers.

PubMed

Clonfero, E; Granella, M; Marchioro, M; Barra, E L; Nardini, B; Ferri, G; Foà, V

1995-03-01

The influence of occupational exposure to polycyclic aromatic hydrocarbons (PAHs) on urinary mutagenic activity was assessed in 75 coke oven workers, using a highly sensitive bacterial mutagen technique (extraction with C18 resin and liquid micro-preincubation test on strain TA98 of Salmonella typhimurium in the presence of metabolizing and deconjugating enzymes). Exposure to PAHs was assessed according to the urinary excretion of 1-pyrenol; the main confounding factors were checked by the number of cigarettes smoked per day and the levels of nicotine and its metabolites in urine, or by ascertaining whether recommended dietary restrictions had been followed. Of the 20 urine samples which turned out to be positive (producing at least double the number of spontaneous revertants), 19 (95%) belonged to smokers. Only one non-smoker had obvious urinary mutagenic activity, and was highly exposed occupationally to PAHs (urinary 1-pyrenol of 3.930 mumol/mol of creatinine). Of the five urine samples from subjects who had not followed the recommended diet, two (40%) were clearly mutagenic. Multiple regression analysis (n = 67) showed that the presence of samples positive for urinary mutagenic activity depended only on smoking habits, if this confounding factor was assessed according to the number of cigarettes smoked per day, while the significant influence of exposure to PAH could be shown when the confounding factor was objectively estimated according to the urinary levels of nicotine and its metabolites. Assessment of the mutagenic potency of urinary extracts (net revertants/mmol creatinine) confirmed the strong influence of smoking habits on urinary mutagenic activity (all smokers 2156 +/- 2691 versus non-smokers 939 +/- 947 net revertants/mmol creatinine; Mann-Whitney test: P < 0.01). In smokers highly exposed to PAHs, greater excretion of mutagens with respect to low-exposure smokers was revealed (3548 +/- 4009 versus 1552 +/- 1227 net revertants/mmol creatinine; Mann

Biodegradability, toxicity and mutagenicity of detergents: Integrated experimental evaluations.

PubMed

Pedrazzani, Roberta; Ceretti, Elisabetta; Zerbini, Ilaria; Casale, Rosario; Gozio, Eleonora; Bertanza, Giorgio; Gelatti, Umberto; Donato, Francesco; Feretti, Donatella

2012-10-01

The widespread use of detergents has raised concern with regard to the environmental pollution caused by their active ingredients, which are biorefractory, toxic and persistent. Since detergents are complex mixtures of different substances, in which synergistic effects may occur, we aimed to assess the mutagenicity of different detergent formulations, taking into account aquatic toxicity and ready biodegradability. We performed a ready biodegradability test (OECD 301 F), Daphnia magna and Vibrio fischeri toxicity tests, and mutagenicity tests (Salmonella/microsome test, Allium cepa test and comet assay). Six detergent formulations were examined, 3 pre-manufacture and 3 commercially available. All detergents presented ready biodegradability. EC50 values varied for all products, according to the marker organism used, but were always higher than the more stringent value considered for aquatic toxicity assessment (V. fischeri 10-60 mg/L; D. magna 25-300 mg/L; A. cepa 250-2000 mg/L). None of the detergents caused mutations in bacteria. However, one commercial ecolabelled product induced an increase in micronucleus frequency in A. cepa root cells. All pre-manufacture detergents and one commercial one, which gave negative results in the Ames and A. cepa tests, induced DNA damage in human leukocytes. A more accurate evaluation of the environmental impact of complex mixtures such as detergents requires a battery of tests to describe degradation, as well as toxicological and mutagenic features. Copyright © 2012 Elsevier Inc. All rights reserved.

Mutagenic activities of a chlorination by-product of butamifos, its structural isomer, and their related compounds.

PubMed

Kamoshita, Masahiro; Kosaka, Koji; Endo, Osamu; Asami, Mari; Aizawa, Takako

2010-01-01

The mutagenic activities of 5-methyl-2-nitrophenol (5M2NP), a chlorination by-product of butamifos, its structural isomer 2-methyl-5-nitrophenol (2M5NP), and related compounds were evaluated by the Ames assay. The mutagenic activities of 5M2NP and 2M5NP were negative or not particularly high. However, those of their chlorinated derivatives were increased in Salmonella typhimurium strain TA100 and the overproducer strains YG1026, and YG1029 in the absence and/or presence of a rat liver metabolic activation system (S9 mix), particularly for YG1029. The mutagenic activities of 6-chloro-2-methyl-5-nitrophenol (6C2M5NP) in YG1029 in the absence and presence of S9 mix were 70000 and 110000 revertants mg(-1), respectively. When nitro functions of 6C2M5NP and 4-chloro-5-methyl-2-nitrophenol (4C5M2NP) were reduced to amino functions, their mutagenic activities were markedly decreased. The mutagenic activities of 5M2NP and 4C5M2NP were lower than those of 2M5NP and 6C2M5NP, respectively. Thus, it was shown that substituent position is a key factor for the mutagenic activities of methylnitrophenols (MNPs) and related compounds. The mutagenic activities of the extracts of 2M5NP in chlorination increased early during the reaction time and then decreased. The main chlorination by-product contributing to the mutagenic activities of the extracts of 2M5NP in chlorination was 6C2M5NP. The results of chlorination of 2M5NP suggested that MNPs were present as their dichlorinated derivatives or further chlorination by-products in drinking water. Copyright 2009 Elsevier Ltd. All rights reserved.

Ginkgo biloba leaf extract action in scavenging free radicals and reducing mutagenicity and toxicity of cigarette smoke in vivo.

PubMed

Wang, Chang G; Dai, Ya; Li, Dong L; Ma, Kuo Y

2010-01-01

In this study, ginkgo biloba leaf extract (GBE) was added to sample cigarettes, including in the filter (0.8 mg/cigarette) and/or the cut filler (0.8 mg/cigarette). The effects of GBE in scavenging free radicals and reducing mutagenicity and toxicity of cigarette smoke in vivo were investigated. Smoke analysis results indicated that GBE eliminated up to 30% of free radicals. Biological experiments, conducted for both GBE cigarettes and control samples, included the Ames test, acute toxicity, neutral red cytotoxicity assay and chronic toxicity. Results showed that the mutagenicity and toxicity of the GBE cigarettes were lower than for the control cigarettes. A possible mechanism of GBE in scavenging free radicals is discussed in this article.

Mutagenicity of food-derived carcinogens and the effect of antioxidant vitamins.

PubMed

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 < 0.0009) increase in MF was found in animals exposed to MeIQx at 25 mg/kg. PhIP was the most mutagenic of the HCAs, with increases (P < 0.0001) in MF detected at all dose levels compared with controls. Because PhIP was the most mutagenic, it was selected for studies using the dietary antioxidant vitamins. Addition of antioxidant vitamins, singly or in a mixture, caused a significant (P < 0.0001) decrease in PhIP-induced Hprt MF. Vitamin E was the most effective at decreasing Hprt MF. In addition, we determined whether 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 < 0.05) in GPx activity. Also a modest increase in GPx activity was seen in animals that received the antioxidant mixture alone

Detection of Androgenic-Mutagenic Compounds and Potential Autochthonous Bacterial Communities during In Situ Bioremediation of Post-methanated Distillery Sludge

PubMed Central

Chandra, Ram; Kumar, Vineet

2017-01-01

Sugarcane-molasses-based post-methanated distillery waste is well known for its toxicity, causing adverse effects on aquatic flora and fauna. Here, it has been demonstrated that there is an abundant mixture of androgenic and mutagenic compounds both in distillery sludge and leachate. Gas chromatography-mass spectrometry (GC-MS) analysis showed dodecanoic acid, octadecanoic acid, n-pentadecanoic acid, hexadecanoic acid, β-sitosterol, stigmasterol, β-sitosterol trimethyl ether, heptacosane, dotriacontane, lanosta-8, 24-dien-3-one, 1-methylene-3-methyl butanol, 1-phenyl-1-propanol, 5-methyl-2-(1-methylethyl) cyclohexanol, and 2-ethylthio-10-hydroxy-9-methoxy-1,4 anthraquinone as major organic pollutants along with heavy metals (all mg kg-1): Fe (2403), Zn (210.15), Mn (126.30, Cu (73.62), Cr (21.825), Pb (16.33) and Ni (13.425). In a simultaneous analysis of bacterial communities using the restriction fragment length polymorphism (RFLP) method the dominance of Bacillus sp. followed by Enterococcus sp. as autochthonous bacterial communities growing in this extremely toxic environment was shown, indicating a primary community for bioremediation. A toxicity evaluation showed a reduction of toxicity in degraded samples of sludge and leachate, confirming the role of autochthonous bacterial communities in the bioremediation of distillery waste in situ. PMID:28567033

Mutagenicity of drinking water sampled from the Yangtze River and Hanshui River (Wuhan section) and correlations with water quality parameters.

PubMed

Lv, Xuemin; Lu, Yi; Yang, Xiaoming; Dong, Xiaorong; Ma, Kunpeng; Xiao, Sanhua; Wang, Yazhou; Tang, Fei

2015-03-31

A total of 54 water samples were collected during three different hydrologic periods (level period, wet period, and dry period) from Plant A and Plant B (a source for Yangtze River and Hanshui River water, respectively), and several water parameters, such as chemical oxygen demand (COD), turbidity, and total organic carbon (TOC), were simultaneously analyzed. The mutagenicity of the water samples was evaluated using the Ames test with Salmonella typhimurium strains TA98 and TA100. According to the results, the organic compounds in the water were largely frame-shift mutagens, as positive results were found for most of the tests using TA98. All of the finished water samples exhibited stronger mutagenicity than the relative raw and distribution water samples, with water samples collected from Plant B presenting stronger mutagenic strength than those from Plant A. The finished water samples from Plant A displayed a seasonal-dependent variation. Water parameters including COD (r = 0.599, P = 0.009), TOC (r = 0.681, P = 0.02), UV254 (r = 0.711, P = 0.001), and total nitrogen (r = 0.570, P = 0.014) exhibited good correlations with mutagenicity (TA98), at 2.0 L/plate, which bolsters the argument of the importance of using mutagenicity as a new parameter to assess the quality of drinking water.

Mutagenicity of drinking water sampled from the Yangtze River and Hanshui River (Wuhan section) and correlations with water quality parameters

PubMed Central

Lv, Xuemin; Lu, Yi; Yang, Xiaoming; Dong, Xiaorong; Ma, Kunpeng; Xiao, Sanhua; Wang, Yazhou; Tang, Fei

2015-01-01

A total of 54 water samples were collected during three different hydrologic periods (level period, wet period, and dry period) from Plant A and Plant B (a source for Yangtze River and Hanshui River water, respectively), and several water parameters, such as chemical oxygen demand (COD), turbidity, and total organic carbon (TOC), were simultaneously analyzed. The mutagenicity of the water samples was evaluated using the Ames test with Salmonella typhimurium strains TA98 and TA100. According to the results, the organic compounds in the water were largely frame-shift mutagens, as positive results were found for most of the tests using TA98. All of the finished water samples exhibited stronger mutagenicity than the relative raw and distribution water samples, with water samples collected from Plant B presenting stronger mutagenic strength than those from Plant A. The finished water samples from Plant A displayed a seasonal-dependent variation. Water parameters including COD (r = 0.599, P = 0.009), TOC (r = 0.681, P = 0.02), UV254 (r = 0.711, P = 0.001), and total nitrogen (r = 0.570, P = 0.014) exhibited good correlations with mutagenicity (TA98), at 2.0 L/plate, which bolsters the argument of the importance of using mutagenicity as a new parameter to assess the quality of drinking water. PMID:25825837

We Are Ames

NASA Image and Video Library

2015-01-26

Ames Research Center, one of NASA's ten field Centers, is located in the heart of California's Silicon Valley. For 75 years, Ames has led the Agency and the country in conducting world-class research and development. Let some of Ames' employees tell you about the work that they do.

Chemopreventive effect and lack of genotoxicity and mutagenicity of the exopolysaccharide botryosphaeran on human lymphocytes.

PubMed

Malini, M; Camargo, M S; Hernandes, L C; Vargas-Rechia, C G; Varanda, E A; Barbosa, A M; Dekker, R F H; Matsumoto, S T; Antunes, L M G; Cólus, I M S

2016-10-01

Carbohydrate biopolymers of fungal-origin are an important natural resource in the search for new bioagents with therapeutic and nutraceutical potential. In this study the mutagenic, genotoxic, antigenotoxic and antioxidant properties of the fungal exopolysaccharide botryosphaeran, a (1→3)(1→6)-β-D-glucan, from Botryosphaeria rhodina MAMB-05, was evaluated. The mutagenicity was assessed at five concentrations in Salmonella typhimurium by the Ames test. Normal and tumor (Jurkat cells) human T lymphocyte cultures were used to evaluate the genotoxicity and antigenotoxicity (Comet assay) of botryosphaeran alone and in combination with the mutagen methyl methanesulfonate (MMS). The ability of botryosphaeran to reduce the production of reactive oxygen and nitrogen species (RONS) generated by hydrogen peroxide was assessed using the CM-H2DCFDA probe in lymphocyte cultures under different treatment times. None of the evaluated botryosphaeran concentrations were mutagenic in bacteria, nor induced genotoxicity in normal and tumor lymphocytes. Botryosphaeran protected lymphocyte DNA against damage caused by MMS under simultaneous treatment and post-treatment conditions. However, botryosphaeran was not able to reduce the RONS generated by H2O2. Besides the absence of genotoxicity, botryosphaeran exerted a protective effect on human lymphocytes against genotoxic damage caused by MMS. These results are important in the validation of botryosphaeran as a therapeutic agent targeting health promotion. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mutagenicity and estrogenicity of raw water and drinking water in an industrialized city in the Yangtze River Delta.

PubMed

Xiao, Sanhua; Lv, Xuemin; Zeng, Yifan; Jin, Tao; Luo, Lan; Zhang, Binbin; Zhang, Gang; Wang, Yanhui; Feng, Lin; Zhu, Yuan; Tang, Fei

2017-10-01

Public concern was aroused by frequently reported water pollution incidents in Taihu Lake and the Yangtze River. The pollution also caught and sustained the attention of the scientific community. From 2010 to 2016, raw water and drinking water samples were continually collected at Waterworks A and B (Taihu Lake) and Waterworks C (Yangtze River). The non-volatile organic pollutants in the water samples were extracted by solid phase extraction. Ames tests and yeast estrogen screen (YES) assays were conducted to evaluate the respective mutagenic and estrogenic effects. Water samples from the Yangtze River-based Waterworks C possessed higher mutagenicity than those from Taihu Lake-based Waterworks A (P＜0.001) and Waterworks B (P = 0.026). Water treatment enhanced the direct mutagenicity (P = 0.022), and weakened the estrogenicity of the raw water (P＜0.001) with a median removal rate of 100%. In fact, very few of the finished samples showed estrogenic activity. Raw water samples from Waterworks A showed weaker estrogenicity than those from Waterworks B (P = 0.034) and Waterworks C (P = 0.006). In summary, mutagenic effects in drinking water and estrogenic effects in raw water merited sustained attention. The Yangtze River was more seriously polluted by mutagenic and estrogenic chemicals than Taihu Lake was. Copyright © 2017 Elsevier Ltd. All rights reserved.

Investigation of toxicity and mutagenicity of cold atmospheric argon plasma.

PubMed

Maisch, T; Bosserhoff, A K; Unger, P; Heider, J; Shimizu, T; Zimmermann, J L; Morfill, G E; Landthaler, M; Karrer, S

2017-04-01

Cold atmospheric argon plasma is recognized as a new contact free approach for the decrease of bacterial load on chronic wounds in patients. So far very limited data are available on its toxicity and mutagenicity on eukaryotic cells. Thus, the toxic/mutagenic potential of cold atmospheric argon plasma using the MicroPlaSter β ® , which has been used efficiently in humans treating chronic and acute wounds, was investigated using the XTT assay in keratinocytes and fibroblasts and the HGPRT (hypoxanthine guanine phosphoribosyl transferase) assay with V79 Chinese hamster cells. The tested clinical parameter of a 2 min cold atmospheric argon plasma treatment revealed no relevant toxicity on keratinocytes (viability: 76% ± 0.17%) and on fibroblasts (viability: 81.8 ± 0.10) after 72 hr as compared to the untreated controls. No mutagenicity was detected in the HGPRT assay with V79 cells even after repetitive CAP treatments of 2-10 min every 24 hr for up to 5 days. In contrast, UV-C irradiation of V79 cells, used as a positive control in the HGPRT test, led to DNA damage and mutagenic effects. Our findings indicate that cold atmospheric plasma using the MicroPlaSter β ® shows negligible effects on keratinocytes and fibroblasts but no mutagenic potential in the HGPRT assay, indicating a new contact free safe technology. Environ. Mol. Mutagen. 58:172-177, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Evidence for the presence of mutagenic arylamines in human breast milk and DNA adducts in exfoliated breast ductal epithelial cells.

PubMed

Thompson, Patricia A; DeMarini, David M; Kadlubar, Fred F; McClure, Gail Y; Brooks, Lance R; Green, Bridgett L; Fares, Manal Y; Stone, Angie; Josephy, P David; Ambrosone, Christine B

2002-01-01

Aromatic and heterocyclic amines are ubiquitous environmental mutagens present in combustion emissions, fried meats, and tobacco smoke, and are suspect human mammary carcinogens. To determine the presence of arylamines in breast tissue and fluid, we examined exfoliated breast ductal epithelial cells for DNA adducts and matched human milk samples for mutagenicity. Breast milk was obtained from 50 women who were 4-6 weeks postpartum, and exfoliated epithelial-cell DNA was evaluated for bulky, nonpolar DNA adducts by (32)P-postlabeling and thin-layer chromatography. Milk was processed by acid hydrolysis, and the extracted organics were examined in the standard plate-incorporation Ames Salmonella assay using primarily strain YG1024, which detects frameshift mutations and overexpresses aryl amine N-acetyltransferase. DNA adducts were identified in 66% of the specimens, and bulky adducts migrated in a pattern similar to that of 4-aminobiphenyl standards. The distribution of adducts did not vary by NAT2 genotype status. Of whole milk samples, 88% (22/25) had mutagenic activity. Among the samples for which we had both DNA adduct and mutagenicity data, 58% (14/19) of the samples with adducts were also mutagenic, and 85% (11/13) of the mutagenic samples had adducts. Quantitatively, no correlation was observed between the levels of adducts and the levels of mutagenicity. Separation of the milk showed that mutagenic activity was found in 69% of skimmed milk samples but in only 29% of the corresponding milk fat samples, suggesting that the breast milk mutagens were moderately polar molecules. Chemical fractionation showed that mutagenic activity was found in 67% (4/6) of the basic fractions but in only 33% (2/6) of acidic samples, indicating that the mutagens were primarily basic compounds, such as arylamines. Although pilot in nature, this study corroborates previous findings of significant levels of DNA adducts in breast tissue and mutagenicity in human breast milk and

Mutagenicity study of weeds and common plants used in traditional medicine and for animal feed.

PubMed

Thepouyporn, Apanchanid; Kwanbunjan, Karunee; Pooudong, Somchai; Changbumrung, Supranee

2006-01-01

Mutagenicity and antimutagenicity potentials were tested using Ames' test in crude distilled water and absolute ethanol extracts from the stems and leaves of Peperomia pellucida (Linn.) Kunth, Eichhornia crassipes Solms, Colocasia esculenta Schott and Brachiaria mutica (Forssk.) Stapf, and the stems of Musa sapientum Linn. No mutagenic effect was found in any of the 10 mg/plate crude extracts of these plants for either TA98 or TA100 of Salmonella typhimurium, in a direct test and a mutagenic induced test by S-9 mix. Both distilled water and absolute ethanol extract of 0.5-10 mg/plate B. mutica showed strong antimutagenicity to AFB1, B(a)P and 4NQO in two tester strains. Ethanol extract of 0.1-0.5 mg/plate C. esculenta also showed antimutagenicity to AFB1, B(a)P and 4NQO in two tester strains, but the 0.5-10 mg/plate water extract had an antimutagenic effect only for B(a)P in TA98. The ethanol extracts of 5 mg/plate B. mutica and 0.5 mg/plate C. esculenta are cytotoxic, as indicated by their partial killing effect.

EVALUATION OF THE MUTAGENIC ACTIVITY OF 3-NBA (3-NITROABENZANTHRONE) USING STRAINS OF SALMONELLA TYPHIMURIUM WITH DIFFERENT LEVELS OF THE ENZYMES NITROREDUCTASE AND ACETYLTRANSFERASE

EPA Science Inventory

The 3-NBA (3-nitro-7H- benz[d,e]antracen-7-one) is extremely potent in the Ames test an useful test for mutagenicity, being a possible inducer of tumors in animals and possible carcinogen for human beings. 3-NBA was previously identified in the exhausts of diesel, particulate mat...

Evolution of the deaminase fold and multiple origins of eukaryotic editing and mutagenic nucleic acid deaminases from bacterial toxin systems

PubMed Central

Iyer, Lakshminarayan M.; Zhang, Dapeng; Rogozin, Igor B.; Aravind, L.

2011-01-01

The deaminase-like fold includes, in addition to nucleic acid/nucleotide deaminases, several catalytic domains such as the JAB domain, and others involved in nucleotide and ADP-ribose metabolism. Using sensitive sequence and structural comparison methods, we develop a comprehensive natural classification of the deaminase-like fold and show that its ancestral version was likely to operate on nucleotides or nucleic acids. Consequently, we present evidence that a specific group of JAB domains are likely to possess a DNA repair function, distinct from the previously known deubiquitinating peptidase activity. We also identified numerous previously unknown clades of nucleic acid deaminases. Using inference based on contextual information, we suggest that most of these clades are toxin domains of two distinct classes of bacterial toxin systems, namely polymorphic toxins implicated in bacterial interstrain competition and those that target distantly related cells. Genome context information suggests that these toxins might be delivered via diverse secretory systems, such as Type V, Type VI, PVC and a novel PrsW-like intramembrane peptidase-dependent mechanism. We propose that certain deaminase toxins might be deployed by diverse extracellular and intracellular pathogens as also endosymbionts as effectors targeting nucleic acids of host cells. Our analysis suggests that these toxin deaminases have been acquired by eukaryotes on several independent occasions and recruited as organellar or nucleo-cytoplasmic RNA modifiers, operating on tRNAs, mRNAs and short non-coding RNAs, and also as mutators of hyper-variable genes, viruses and selfish elements. This scenario potentially explains the origin of mutagenic AID/APOBEC-like deaminases, including novel versions from Caenorhabditis, Nematostella and diverse algae and a large class of fast-evolving fungal deaminases. These observations greatly expand the distribution of possible unidentified mutagenic processes catalyzed by

Characterization and Quantification of Compounds in the Hydroalcoholic Extract of the Leaves from Terminalia catappa Linn. (Combretaceae) and Their Mutagenic Activity

PubMed Central

Mininel, Francisco José; Leonardo Junior, Carlos Sérgio; Espanha, Lívia Greghi; Resende, Flávia Aparecida; Varanda, Eliana Aparecida; Leite, Clarice Queico Fujimura; Vilegas, Wagner; dos Santos, Lourdes Campaner

2014-01-01

Terminalia is a genus of Combretaceous plants widely distributed in tropical and subtropical regions. Thus, the aim of this study was to quantify the majority compounds of the hydroalcoholic extract (7 : 3, v/v) of the leaves from T. catappa by HPLC-PDA, chemically characterize by hyphenated techniques (HPLC-ESI-IT-MSn) and NMR, and evaluate its mutagenic activity by the Salmonella/microsome assay on S. typhimurium strains TA98, TA97a, TA100, and TA102. The quantification of analytes was performed using an external calibration standard. Punicalagin is the most abundant polyphenol found in the leaves. The presence of this compound as a mixture of anomers was confirmed using HPLC-PDA and 1H and 13C NMR. Mutagenic activity was observed in strains TA100 and TA97a. As the extract is a complex mixture of punicalagin, its derivatives, and several other compounds, the observed mutagenicity may be explained in part by possible synergistic interaction between the compounds present in the extract. These studies show that mutagenic activity of T. catappa in the Ames test can only be observed when measured at high concentrations. However, considering the mutagenic effects observed for T. catappa, this plant should be used cautiously for medicinal purposes. PMID:24734110

[Mutagenicity study of water samples from a waterworks taking Yangtze River as its water source in Jiangsu Province].

PubMed

Xiao, Sanhua; Luo, Lan; Qiao, Qian; Lü, Xuemin; Wang, Yanhui; Feng, Lin; Tang, Fei; Wang, Haiyong; Bie, Nana; Wang, Yuehong

2017-05-01

To understand the occurrence and change of mutagencity of water samples in the process of drinking water treatment and distribution in a waterworks taking Yangtze River as its water source in Jiangsu Province. Large volume of inlet water, finished water and tap water samples were extracted by XAD-2 resin. Mutagencities were assessed by Ames test and a mutation ratio( MR) of 2 or greater was judged as a positive result. Compared with the samples with S9, samples without S9 presented more positive results( P = 0. 005). That water treatment elevated MR values( P = 0. 007) while the pipe transport made MR values down( P = 0. 038) was observed in samples without S9. The tap water showed weaker mutagenicities than the raw water in samples with S9( P = 0. 008). Compared to the raw water samples, the finished water samples showed more positive results(-S9) and lower MR values( + S9, P =0. 002). Significant mutagenicities of water samples from the Yangtze Riverand its processed water were presented, and frame shit and direct mutagens deserved special concern.

Safety and mutagenicity evaluation of red mold dioscorea fermented from Monascus purpureus NTU 568.

PubMed

Hsu, Li-Chuan; Hsu, Ya-Wen; Hong, Chih-Chun; Pan, Tzu-Ming

2014-05-01

Monascus-fermented products, including red mold rice and red mold dioscorea, have been developed as functional foods with many health benefits. We performed safety and mutagenic evaluations on red mold dioscorea powder (RMDP) fermented from Monascus purpureus NTU 568. The results of Ames test using Salmonella typhimurium strains TA97a, TA98, TA100, TA102, and TA1535 showed that RMDP (⩽5 mg/plate) was not mutagenic. The mammalian chromosomal aberration test showed that the number of Chinese hamster ovary cells with abnormal chromosomes was <3% after RMDP treatment (maximum concentration: 5 mg/mL). Imprinting control region mice were used to estimate the genotoxicity of RMDP. Compared with the control, high-dose RMDP administration (2000 mg/kg) did not show significant differences in the number of reticulocytes or the occurrence of micronucleated reticulocytes. A 28-day oral toxicity assay in Sprague-Dawley rats was performed to investigate the no observed adverse effect level of RMDP. Compared with the control, high-dose RMDP administration (2000 mg/kg) caused no toxicological responses such as mortality, variation in body weight, or toxicopathologic lesions. Thus, RMDP from M. purpureus NTU 568 shows no significant mutagenic or toxic effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

Approach for detecting mutagenicity of biodegraded and ozonated pharmaceuticals, metabolites and transformation products from a drinking water perspective.

PubMed

Gartiser, Stefan; Hafner, Christoph; Kronenberger-Schäfer, Kerstin; Happel, Oliver; Trautwein, Christoph; Kümmerer, Klaus

2012-09-01

Many pharmaceuticals and related metabolites are not efficiently removed in sewage treatment plants and enter into surface water. There, they might be subject of drinking water abstraction and treatment by ozonation. In this study, a systematic approach for producing and effect-based testing of transformation products (TPs) during the drinking water ozonation process is proposed. For this, two pharmaceutical parent substances, three metabolites and one environmental degradation product were investigated with respect to their biodegradability and fate during drinking water ozonation. The Ames test (TA98, TA100) was used for the identification of mutagenic activity present in the solutions after testing inherent biodegradability and/or after ozonation of the samples. Suspicious results were complemented with the umu test. Due to the low substrate concentration required for ozonation, all ozonated samples were concentrated via solid phase extraction (SPE) before performing the Ames test. With the exception of piracetam, all substances were only incompletely biodegradable, suggesting the formation of stable TPs. Metformin, piracetam and guanylurea could not be removed completely by the ozonation process. We received some evidence that technical TPs are formed by ozonation of metformin and piracetam, whereas all tested metabolites were not detectable by analytical means after ozonation. In the case of guanylurea, one ozonation TP was identified by LC/MS. None of the experiments showed an increase of mutagenic effects in the Ames test. However, the SPE concentration procedure might lead to false-positive results due to the generation of mutagenic artefacts or might lead to false-negative results by missing adequate recovery efficiency. Thus, these investigations should always be accompanied by process blank controls that are carried out along the whole ozonation and SPE procedure. The study presented here is a first attempt to investigate the significance of

Ultra high performance liquid chromatography with tandem mass spectrometry screening and mutagenicity evaluation of photodegradation products of Carmoisine (E122) dye in a beverage.

PubMed

Yamjala, Karthik; Nainar, Meyyanathan Subramania; Ramisetti, Nageswara Rao

2016-06-01

The present study deals with the separation and identification of the photodegradation products formed when a commercial soft drink containing Carmoisine (E122) dye was exposed to natural sunlight. An ultra high performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry method was developed and validated to identify the unknown species of E122. During the study, it was observed that the dye decolourizes rapidly in beverage when compared to model standard solutions. The sunlight irradiation of beverage containing E122 resulted in four photodegradation products as identified by nontarget screening using high-resolution tandem mass spectrometry. Accurate mass measurements were used to identify the elemental composition, and to elucidate the structures of degradation products a software tool was employed. The degradation products (P1-P4) were formed from the interactions of the dye with other ingredients present in the beverage. The toxicity of the degradation products was evaluated on five bacterial strains (TA98, TA100, TA1535, TA1537, and WP2 uvrA pKM101) through an in vitro bacterial reverse mutation assay. The photodegradation products showed strong mutagenic potential in strain TA 100 (without S9) as detected by the Ames assay. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ames Lab 101: Danny Shechtman Returns to the Ames Laboratory

ScienceCinema

Shechtman, Danny

2018-05-07

Danny Shechtman, Ames Laboratory Scientist and winner of the Nobel Prize in Chemistry 2011, returned to the Ames Lab on February 14, 2012. During this time, the Nobel Laureate met with the press as well as ISU students.

Cytotoxicity and mutagenicity studies on migration extracts from nanocomposites with potential use in food packaging.

PubMed

Maisanaba, Sara; Pichardo, Silvia; Jordá-Beneyto, María; Aucejo, Susana; Cameán, Ana M; Jos, Ángeles

2014-04-01

Clays are used in the food packaging industry to obtain nanocomposites. The use of these new materials is a concern, because they could reach consumers by oral exposure through possible migration, and potential toxic effects could be derived. In the present study, several in vitro basal cytotoxicity and mutagenicity tests on migration extracts obtained from a nanocomposite material with poly (lactic) acid (PLA) and two modified clays, Clay1 and Clay2, are shown. Migration extracts in distilled water showed values of 0.1 ± 0.2mg/dm(2) in all samples. Also, the content of characteristic metals of the clays structure (Al, Ca, Mg, Fe, Si) was studied and no statistical differences were observed. For the cytotoxicity assays, the human intestinal Caco-2 and human liver HepG2 cells were selected. Cells were exposed to concentrations between 2.5% and 100% extracts determining three different biomarkers of cellular viability. No significant differences were observed in the cytotoxicity assays. Finally, mutagenicity was evaluated by the Ames test and resulted in the absence of mutagenic response at all the concentrations assayed. Taking in account all above mentioned, these new materials show a good profile for their use in food packaging although further research is still needed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Acute biotoxic effect of styrene on rat liver. Correlation with enzyme-mediated mutagenicity of benzpyrene and acrylonitrile.

PubMed

Roberfroid, M; Poncelet, F; Lambotte-Vandepaer, M; Duverger-Van Bogaert, M; de Meester, C; Mercier, M

1978-01-01

Styrene is commonly used in western Europe for the manufacture of plastics suitable for packaging foodstuffs. This report demonstrates that, injected intraperitoneally at a dose as low as 10 mg/kg, styrene modifies the catalytic properties of aryl hydrocarbon hydroxylase by reducing its KM value. A similar effect is reported for two potent chemical carcinogens, 3-methylcholanthrene and benzo(a)pyrene. Ethylbenzene and benzo(e)pyrene and phenobarbital do not produce the same effect. Pretreatments of the rats with chemicals which modify aryl hydrocarbon hydroxylase also increase the capacity of the liver enzymes to activate benzopyrene to a mutagenic intermediate in vitro, as measured by the Ames test for mutagenicity. Exposure to both styrene and the other modifiers of the xenobiotic-metabolizing enzymes could thus influence the carcinogenic and toxic effects of chemicals which are activated by these enzymes. This hypothesis needs further investigation.

An investigation of interurban variations in the chemical composition and mutagenic activity of airborne particulate organic matter using an integrated chemical class/bioassay system

NASA Astrophysics Data System (ADS)

Butler, J. P.; Kneip, T. J.; Daisey, J. M.

Previous investigations in this laboratory have demonstrated that the mutagenic activities of extractable particulate organic matter (EOM) from cities which differ in their principal fuels and meteorology can vary significantly. To gain a better understanding of these interurban variations, an Integrated Chemical Class/Biological Screening System was developed and used for a more detailed examination of differences in the chemical composition and mutagenic activity of EOM. The screening system involved coupling in situ Ames mutagenicity determinations on high performance thin layer chromatography (HPTLC) plates with class specific chemical analyses on a second set of plates. The system was used to screen for mutagenic activity and selected chemical classes (including PAH, nitro-PAH, phenols, carboxylic acids, carbonyls, aza-arenes and alkylating agents) in EOM from the following sites: New York City; Elizabeth, N.J.; Mexico City; Beijing, China; Philadelphia, PA; and the Caldecott Tunnel (CA). The results of this study demonstrated mutagenic activity and chemical compositional differences in HPTLC subfractions of particulate organic matter from these cities and from the Caldecott Tunnel. The greatest interurban differences in chemical classes were observed for the phenols, carbonyl compounds and alkylating agents. Interurban variations in mutagenic activities were greatest for EOM subfractions of intermediate polarity. These differences are probably related to interurban differences in the fuels used, types of sources and atmospheric conditions. The relationships between these variables are not well understood at present.

Carbamates and ICH M7 classification: Making use of expert knowledge.

PubMed

Hemingway, Rachel; Fowkes, Adrian; Williams, Richard V

2017-06-01

Carbamates are widely used in the chemical industry so understanding their toxicity is important to safety assessment. Carbamates have been associated with certain toxicities resulting in publication of structural alerts, including alerts for mutagenicity. Structural alerts for bacterial mutagenicity can be used in combination with statistical systems to enable ICH M7 classification, which allows assessment of the genotoxic risk posed by pharmaceutical impurities. This study tested a hypothetical bacterial mutagenicity alert for carbamates and examined the impact it would have on ICH M7 classifications using (Q)SAR predictions from the expert rule-based system Derek Nexus and the statistical-based system Sarah Nexus. Public datasets have a low prevalence of mutagenic carbamates, which highlighted that systems containing an alert for carbamates perform poorly for achieving correct ICH M7 classifications. Carbamates are commonly used as protecting groups and proprietary datasets containing such compounds were also found to have a low prevalence of mutagenic compounds. Expert review of the mutagenic compounds established that mutagenicity was often only observed under certain (non-standard) conditions and more generally that the Ames test may be a poor predictor for the risk of carcinogenicity posed by chemicals in this class. Overall a structural alert for the in vitro bacterial mutagenesis of carbamates does not benefit workflows for assigning ICH M7 classification to impurities. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Microbiology and potential applications of aerobic methane oxidation coupled to denitrification (AME-D) process: A review.

PubMed

Zhu, Jing; Wang, Qian; Yuan, Mengdong; Tan, Giin-Yu Amy; Sun, Faqian; Wang, Cheng; Wu, Weixiang; Lee, Po-Heng

2016-03-01

Aerobic methane oxidation coupled to denitrification (AME-D) is an important link between the global methane and nitrogen cycles. This mini-review updates discoveries regarding aerobic methanotrophs and denitrifiers, as a prelude to spotlight the microbial mechanism and the potential applications of AME-D. Until recently, AME-D was thought to be accomplished by a microbial consortium where denitrifying bacteria utilize carbon intermediates, which are excreted by aerobic methanotrophs, as energy and carbon sources. Potential carbon intermediates include methanol, citrate and acetate. This mini-review presents microbial thermodynamic estimations and postulates that methanol is the ideal electron donor for denitrification, and may serve as a trophic link between methanotrophic bacteria and denitrifiers. More excitingly, new discoveries have revealed that AME-D is not only confined to the conventional synergism between methanotrophic bacteria and denitrifiers. Specifically, an obligate aerobic methanotrophic bacterium, Methylomonas denitrificans FJG1, has been demonstrated to couple partial denitrification with methane oxidation, under hypoxia conditions, releasing nitrous oxide as a terminal product. This finding not only substantially advances the understanding of AME-D mechanism, but also implies an important but unknown role of aerobic methanotrophs in global climate change through their influence on both the methane and nitrogen cycles in ecosystems. Hence, further investigation on AME-D microbiology and mechanism is essential to better understand global climate issues and to develop niche biotechnological solutions. This mini-review also presents traditional microbial techniques, such as pure cultivation and stable isotope probing, and powerful microbial techniques, such as (meta-) genomics and (meta-) transcriptomics, for deciphering linked methane oxidation and denitrification. Although AME-D has immense potential for nitrogen removal from wastewater, drinking

Mutagenic and genotoxic effects of Guelma's urban wastewater, Algeria.

PubMed

Tabet, Mouna; Abda, Ahlem; Benouareth, Djamel E; Liman, Recep; Konuk, Muhsin; Khallef, Messaouda; Taher, Ali

2015-02-01

Assessment of water pollution and its effect upon river biotic communities and human health is indispensable to develop control and management strategies. In this study, the mutagenicity and genotoxicity of urban wastewater of the city of Guelma in Algeria were examined between April 2012 and April 2013. For this, two biological tests, namely Amesand chromosomal aberrations (CA) test in Allium cepa root tips were employed on the samples collected from five different sampling stages (S1-S5). In Ames test, two strains of Salmonella typhimurium TA98 and TA100 with or without metabolic activation (S9-mix) were used. All water samples were found to be mutagenic to S. typhimurium TA98 with or without S9-mix. A significant decrease in mitotic index (MI) was observed with a decrease in the percentage of cells in the prophase and an increase in the telophase. Main aberrations observed were anaphase bridges, disturbed anaphase-telophase cells, vagrants and stickiness in anaphase-telophase cells. All treatments of wastewater in April 2012, at S5 in July 2012, at S1 and S5 in November 2012, at S5 in February 2013, and at S1 in April 2013 induced CA when compared to the negative control. Some physicochemical parameters and heavy metals (Cd, Pb, and Cu) were also recorded in the samples examined.

Photographer: NASA Ames On 20 December 1989, Ames buried a time capsule and unveiled a sculpture at

NASA Technical Reports Server (NTRS)

1989-01-01

Photographer: NASA Ames On 20 December 1989, Ames buried a time capsule and unveiled a sculpture at the spot where, fifty years earlier, Russel Robinson had turned the first spade of dirt for the Ames construction shack: Robinson (left) Ames Director Dale Compton (center) and Ames Deputy Director Sy Syvertson (right)

The Ames Project (1942-1946)

ScienceCinema

None

2018-04-26

The Ames Laboratory was officially founded on May 17, 1947, following development of a process to purify uranium metal for the historic Manhattan Project. From 1942 to 1946, Ames Lab scientists produced over two-million pounds of uranium metal. A U.S. Department of Energy national research laboratory, the Ames Laboratory creates materials and energy solutions. Iowa State University operates Ames Laboratory under contract with the DOE.

Management process invaded Ames as the Center shifted from NACA to NASA oversight. Ames constructed

NASA Technical Reports Server (NTRS)

1968-01-01

Management process invaded Ames as the Center shifted from NACA to NASA oversight. Ames constructed a review room in its headquarters building where, in the graphical style that prevailed in the 1960's, Ames leadership could review progress against schedule, budget and performance measures. Shown, in October 1965 is Merrill Mead chief of Ames' program and resources office. (for H Julian Allen Retirement album)

Ames Fitness Program

NASA Technical Reports Server (NTRS)

Pratt, Randy

1993-01-01

The Ames Fitness Program services 5,000 civil servants and contractors working at Ames Research Center. A 3,000 square foot fitness center, equipped with cardiovascular machines, weight training machines, and free weight equipment is on site. Thirty exercise classes are held each week at the Center. A weight loss program is offered, including individual exercise prescriptions, fitness testing, and organized monthly runs. The Fitness Center is staffed by one full-time program coordinator and 15 hours per week of part-time help. Membership is available to all employees at Ames at no charge, and there are no fees for participation in any of the program activities. Prior to using the Center, employees must obtain a physical examination and complete a membership package. Funding for the Ames Fitness Program was in jeopardy in December 1992; however, the employees circulated a petition in support of the program and collected more than 1500 signatures in only three days. Funding has been approved through October 1993.

URINARY MUTAGENICITY AS A BIOMARKER OF COOKED-MEAT-ASSOCIATED MUTAGENS AND RISK FOR COLORECTAL ADENOMA

EPA Science Inventory

Urinary Mutagenicity as a Biomarker of Cooked-Meat-Associated Mutagens and Risk for Colorectal Adenoma

In a controlled feeding study involving 60 subjects, we have investigated urinary mutagenicity as a biomarker of exposure to cooked-meat-associated mutagens. In a separa...

The effect of green tea and olive oil on the mutagenic activity of heterocyclic amines extracted from common food consumed in Saudi Arabia.

PubMed

Awney, Hala

2011-05-01

The effect of green tea (GT) and green tea with olive oil (GT+OL) as antioxidants on the formation and mutagenic activity of heterocyclic aromatic amines (HCAs) extracted from beef shawerma, grilled chicken and fried beef liver was examined. HCAs were extracted by blue rayon, analyzed as spiked and unspiked samples with high-performance liquid chromatography and its mutagenic response was assessed by Sallmonela typhimurium 100 in the Ames test. Surprisingly, GT and GT+OL augmented HCAs measured in beef shawerma and grilled chicken but total HCAs measured in GT+OL were less than GT treatment. Both treatments altered the HCA profile as imidazoquinoline type became the most abundant. In control and GT+OL fried beef liver no HCAs were detected, but Trp-P1 was detected in GT treatment. Generally, the mutagenic response of HCAs measured in GT+OL was less than GT in beef shawerma and grilled chicken. However, the mutagenic response of control and 2% GT+OL fried liver was negative. These data suggest that GT concentrations used in this study may induce free radical formation during the Millared reaction due to its pro-oxidative effect, which augmented the HCAs formed and its mutagenic response. In order to optimize both safety and quality of our diets, more need to be done to fully understand the risk of HCAs in food.

Mutagenicity of aerosols from the oxidative thermal decomposition of rigid polyurethane foam.

PubMed

Zitting, A; Falck, K; Skyttä, E

1980-01-01

The aerosol fraction of the oxidative thermal decomposition products (700 degrees C) of rigid polyurethane foam was collected on glass fiber filters and fractionated into either-soluble neutral, acidic, and basic fractions and water-soluble compounds. The fractions showed mutagenic activity in a bacterial fluctuation test with Salmonella typhimurium TA98 or Escherichia coli CM891 as the tester strains. All the fractions induced mutations in both strains after metabolic activation with rat liver S-9 mix. The basic and the water-soluble fractions were mutagenic for S. typhimurium TA 98 even without activation. Thin-layer chromatography showed the presence of several primary aromatic amines in the aerosol. Polycyclic aromatic hydrocarbons were not detected by glass capillary gas chromatogaphy.

Mutagenicity and Acute Oral Toxicity Test for Herbal Poultry Feed Supplements.

PubMed

Srinivasa Rao, Boddapati; Chandrasekaran, C V; Srikanth, H S; Sasikumar, Murugan; Edwin Jothie, R; Haseena, Begum; Bharathi, Bethapudi; Selvam, Ramasamy; Prashanth, D'Souza

2018-01-01

Herbal products are being used and trusted globally for thousands of years for their health benefits and limited side effects. Globally, a general belief amongst the consumers is that herbal supplements are always safe because they are "natural." But later, research reveals that they may not be safe. This raises concern on their safety and implications for their use as feed supplement or medicine. Toxicity testing can reveal some of the risks that may be associated with use of herbs, therefore avoiding potential harmful effects. The present study was designed to investigate five poultry feed supplements (PFS), EGMAX® (to revitalize ovarian activity), FEED-X ™ (feed efficiency enhancer), KOLIN PLUS ™ (natural replacer of synthetic choline chloride), PHYTOCEE® (natural defence enhancer), and STODI® (to prevent and control loose droppings), for their possible mutagenicity and toxicity. Bacterial reverse mutation (BRMT) and acute oral toxicity tests were employed to assess the PFS for their possible mutagenicity and toxicity. Results indicated that the PFS were devoid of mutagenic effects in BRMT and showed higher safety profile in rodent acute oral toxicity test.

Structure, mechanical characteristics and in vitro degradation, cytotoxicity, genotoxicity and mutagenicity of novel biodegradable Zn-Mg alloys.

PubMed

Kubásek, J; Vojtěch, D; Jablonská, E; Pospíšilová, I; Lipov, J; Ruml, T

2016-01-01

Zn-(0-1.6)Mg (in wt.%) alloys were prepared by hot extrusion at 300 °C. The structure, mechanical properties and in vitro biocompatibility of the alloys were investigated. The hot-extruded magnesium-based WE43 alloy was used as a control. Mechanical properties were evaluated by hardness, compressive and tensile testing. The cytotoxicity, genotoxicity (comet assay) and mutagenicity (Ames test) of the alloy extracts and ZnCl2 solutions were evaluated with the use of murine fibroblasts L929 and human osteosarcoma cell line U-2 OS. The microstructure of the Zn alloys consisted of recrystallized Zn grains of 12 μm in size and fine Mg2Zn11 particles arranged parallel to the hot extrusion direction. Mechanical tests revealed that the hardness and strength increased with increasing Mg concentration. The Zn-0.8 Mg alloys showed the best combination of tensile mechanical properties (tensile yield strength of 203 MPa, ultimate tensile strength of 301 MPa and elongation of 15%). At higher Mg concentrations the plasticity of Zn-Mg alloys was deteriorated. Cytotoxicity tests with alloy extracts and ZnCl2 solutions proved the maximum safe Zn(2+) concentrations of 120 μM and 80 μM for the U-2 OS and L929 cell lines, respectively. Ames test with extracts of alloys indicated that the extracts were not mutagenic. The comet assay demonstrated that 1-day extracts of alloys were not genotoxic for U-2 OS and L929 cell lines after 1-day incubation. Copyright © 2015 Elsevier B.V. All rights reserved.

Microbial mutagenic effects of the DNA minor groove binder pibenzimol (Hoechst 33258) and a series of mustard analogues.

PubMed

Ferguson, L R; Denny, W A

1995-06-01

A series of aniline mustards and half-mustards targeted to DNA by linkage (through a polymethylene chain) to the bisbenzimidazole chromophore of pibenzimol (Hoechst 33258) have been evaluated for their mutagenic properties, as estimated in three strains of Salmonella typhimurium, and for their mitotic crossing-over and petite mutagenesis activities in Saccharomyces cerevisiae strain D5. Agarose gel electrophoresis studies showed that only the derivative with the longest linker chain cross-linked DNA, with the remaining compounds being monoalkylators. The parent (non-alkylator) minor groove binding ligand (Hoechst 33258) was inactive in the bacterial strains TA98 or TA100 but weakly mutagenic in TA102, and caused neither mitotic crossing-over nor 'petite' mutagenesis in yeast. Aniline half-mustard itself (monoalkylator) was an effective base-pair substitution mutagen (events in S. typhimurium strain TA100) with some frameshift mutagenesis activity in TA98, but showed only weak effects in the yeast assays, whereas aniline mustard (cross-linker) was inactive in these bacterial systems but caused substantial amounts of mitotic crossing-over in yeast. The composite molecules studied here showed effects more characteristic of the minor groove binding chromophore than of alkylating moieties. All showed weak mutagenic activity in TA102 and none in TA98. The only compound to show significant mitotic crossing-over ability was the long-chain derivative which cross-linked DNA. For most of the compounds, the mutagenicity data provided no supportive evidence for DNA alkylation. Since other evidence suggests this does occur readily, it is likely to have a different target to that seen with untargeted aniline mustards. The significant antitumor activity and low mutagenic potential shown by these compounds make them worthy of further study.

Fruit extract of the medicinal plant Crataegus oxyacantha exerts genotoxic and mutagenic effects in cultured cells.

PubMed

de Quadros, Ana Paula Oliveira; Mazzeo, Dania Elisa Christofoletti; Marin-Morales, Maria Aparecida; Perazzo, Fábio Ferreira; Rosa, Paulo Cesar Pires; Maistro, Edson Luis

2017-01-01

Crataegus oxyacantha, a plant of the Rosaceae family also known "English hawthorn, haw, maybush, or whitethorn," has long been used for medicinal purposes such as digestive disorders, hyperlipidemia, dyspnea, inducing diuresis, and preventing kidney stones. However, the predominant use of this plant has been to treat cardiovascular disorders. Due to a lack of studies on the genotoxicity of C. oxyacantha, this investigation was undertaken to determine whether its fruit extract exerts cytotoxic, genotoxic, or clastogenic/aneugenic effects in leukocytes and HepG2 (liver hepatocellular carcinoma) cultured human cells, or mutagenic effects in TA100 and TA98 strains of Salmonella typhimurium bacterium. Genotoxicity analysis showed that the extract produced no marked genotoxic effects at concentrations of 2.5 or 5 µg/ml in either cell type; however, at concentrations of 10 µg/ml or higher significant DNA damage was detected. The micronucleus test also demonstrated that concentrations of 10 µg/ml or higher produced clastogenic/aneugenic responses. In the Ames test, the extract induced mutagenic effects in TA98 strain of S. typhimurium with metabolic activation at all tested concentrations (2.5 to 500 µg/ml). Data indicate that, under certain experimental conditions, the fruit extract of C. oxyacantha exerts genotoxic and clastogenic/aneugenic effects in cultured human cells, and with metabolism mutagenicity occurs in bacteria cells.

[Comutagenic action of sodium selenite and caffeine on S. typhimurium TA 1535 with its subsequent treatment by N-nitrosomethylurea].

PubMed

Balanski, R M

1988-01-01

The comutagenic activity of sodium selenite and caffeine was studied by the Ames test. Reproduction of S. typhimurium TA1535 for 4 h at 37 degrees C in the nutrient broth with sodium selenide (5 micrograms/ml) significantly increased sensitivity of bacterial cells to the mutagenic action of 2-3 mM N-nitrosomethylurea (NMU). When using threshold concentrations of NMU the potentiation of mutagenesis reached 625.2%. The addition of 0.19 mg/ml of caffeine to the nutrient medium also led (though the action was less pronounced) to an increase in sensitivity of bacterial cells to the NMU mutagenic action. Reproduction of S. typhimurium TA1535 in the medium containing sodium selenide and caffeine did not cause an increase in the frequency of spontaneous his+-revertant mutations.

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

PubMed

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

2004-01-10

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

Interlaboratory comparison of mutagenesis testing of coal fly ash derived from differenct coal conversion technologies

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

Chrisp, C.; Hobbs, C.; Clark, R.

1979-01-01

This experiment showed that mutagenicity of fly ash derived from different coal conversion technologies, as determined by the Ames plate incorporation test, was similar in all three laboratories. The differences in mutagenic activity of each fly ash between laboratories with different solvent extraction methods were no greater than one order of magnitude. In addition, there were much smaller, but still significant differences in mutagenic activity between laboratories when the same solvent extract of a particular fly ash was tested in each laboratory. There were also significant differences in mutagenicity of the positive control mutagen (maximum of fivefold) between laboratories. Becausemore » of this difference in Ames test sensitivity between laboratories, the influence of the solvent extraction methods on differences in mutagenicity was not clear. However, the data suggested that either there were significant differences in the degree of sensitivity of Ames tests for different complex mixtures within each laboratory, or else there were differences in mutagen extraction efficiency between different solvent extraction methods. Both Ames test sensitivity and solvent extraction may be important. Further work would be necessary to separate the contribution of these two factors. An important aspect of further work would be to separate the contribution of the innate sensitivity of substrains of Ames tester strains in each laboratory from the possible effects of differences in Ames testing methodology. This could be done by testing the same extracts of fly ash and positive control mutagens with substrains of tester strains exchanged between laboratories. This work also implies that caution should be exercised in assuming that the same solvent would have the same efficiency for extraction of mutagens from different fly ashes even within the same laboratory.« less

Ames Lab 101: Technology Transfer

ScienceCinema

Covey, Debra

2017-12-13

Ames Laboratory Associate Laboratory Director, Sponsored Research Administration, Debra Covey discusses technology transfer. Covey also discusses Ames Laboratory's most successful transfer, lead-free solder.

Mutagenic activity of disinfection by-products

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

Cognet, L.; Courtois, Y.; Mallevialle, J.

1986-11-01

Data on raw water quality, disinfection treatment practices, and the resulting mutagenic properties of the treated water were compiled from pilot- and full-scale treatment experiments to evaluate that parameter which might produce variability in the results of a mutagenic study. Analysis of the data and comparison of treatment practices indicated that the measured mutagenic activity is strongly related to the characteristics of the organic matter in the raw water, the methodology used to sample and detect mutagens, the scale of the study both in terms of treatment flow and period of study, and the point at which and the conditionsmore » under which oxidants are added during treatment. Conclusions regarding disinfection systems in full-scale water treatment plants include the following: When raw water is pretreated and high concentrations of organics are present in the raw water, both ozonation and chlorination increased mutagenic activity. However, no significant difference in mutagenicity was found between the two oxidants. Both in the case of a nitrified groundwater and a clarified surface water, the mutagenic activity of the water after ozonation was related to its mutagenic activity before ozonation. With ozonation, mutagenic activity decreased after granular activated carbon (GAC) filtration. Thus, when GAC filtration follows ozone disinfection, early addition of oxidants may not be deleterious to the finished water quality. When chlorine or chlorine dioxide is added after GAC filtration, chlorine dioxide was found to produce a less mutagenic water than chlorine. Although these conclusions suggest means of controlling mutagenic activity during treatment, it must be stressed that the measurement of mutagenicity is a presumptive index of contamination level.« less

Nitroreductase-dependent mutagenicity of p-nitrophenylhydroxylamine and its N-acetyl and N-formyl hydroxamic acids.

PubMed

Corbett, M D; Wei, C; Corbett, B R

1985-05-01

p-Nitrophenylhydroxylamine (NPH) and two hydroxamic acids derived from it were synthesized and subjected to mutagenicity testing in Salmonella typhimurium strains TA98, TA98NR, TA1538 and TA1538NR. In addition, p-dinitrobenzene (DNB), p-nitroaniline (NA) and p-nitroacetanilide (AcNA) were simultaneously examined for mutagenic action against these four tester strains. NPH, its N-acetyl (AcNPH) and N-formyl (FoNPH) derivatives, and also DNB displayed strong mutagenic action to the nitroreductase-containing strains, TA98 and TA1538. NPH was the most potent chemical in this series against both of these strains, while the two hydroxamic acids AcNPH and FoNPH, and also DNB displayed approximately the same degree of mutagenicity. In the nitroreductase-deficient strains, TA98NR and TA1538NR, the mutagenicity of these four compounds was markedly reduced. The necessity for nitroreduction in order to activate these promutagens is fairly certain; however, the lack of mutagenicity of NA and AcNA towards all four tester strains made the interpretation of these data somewhat more complicated. Several possible bioactivation pathways were presented, with one mechanism in particular being proposed. This mechanism requires only that the strong electron-withdrawing nitro group be converted to an electron-donating group by bacterial nitroreductase. Such a mechanism is unique for the bioactivation of nitro aromatics by nitroreductase, since the enzymatic reduction need not produce the intermediary hydroxylamine metabolite.

Mutagenic activity and metabolites in the urine of workers exposed to trinitrotoluene (TNT).

PubMed Central

Ahlborg, G; Einistö, P; Sorsa, M

1988-01-01

Urine samples taken after work and after a free weekend from 50 workers employed in various activities in a chemical plant manufacturing explosives were analysed. On the basis of hygienic surveys, the subjects were divided into three categories of exposure to trinitrotoluene (TNT). The urine analyses consisted of gas chromatographic identification of TNT and its two metabolites, 4-ADNT and 2-ADNT, and a determination of the mutagenic activity. Two frame shift detector strains of Salmonella typhimurium were used, TA 98 and TA 98 NR, the latter being deficient in endogenous nitroreductase activity. On the basis of previous results on TNT mutagenicity, no exogeneous metabolic system was used to test the urine concentrates. Both tester strains showed that the mean urinary mutagenic activity was higher in the after work samples than in post weekend samples from the same subjects, showing that bacterial nitroreductase activity was not significantly responsible for the mutagenicity, although the response was higher with strain TA 98 than with TA 98 NR. The interindividual variation in urine mutagenicity was high, however, and the difference between the two sampling times was statistically significant (p less than 0.05) only for the high exposed group (workers in trotyl foundry and sieve house). Correlation between urinary mutagenicity and concentration of TNT in urine was poor; correlation was significant only with the urinary concentration of 4-ADNT. The correlation between urinary TNT and both metabolites was good (p less than 0.001). These results suggest that analysis of 4-ADNT in urine would be a sufficient biological measure for controlling exposure to TNT. PMID:3378017

Genotoxicity assessment of magnetic iron oxide nanoparticles with different particle sizes and surface coatings

NASA Astrophysics Data System (ADS)

Liu, Yanping; Xia, Qiyue; Liu, Ying; Zhang, Shuyang; Cheng, Feng; Zhong, Zhihui; Wang, Li; Li, Hongxia; Xiao, Kai

2014-10-01

Magnetic iron oxide nanoparticles (IONPs) have been widely used for various biomedical applications such as magnetic resonance imaging and drug delivery. However, their potential toxic effects, including genotoxicity, need to be thoroughly understood. In the present study, the genotoxicity of IONPs with different particle sizes (10, 30 nm) and surface coatings (PEG, PEI) were assessed using three standard genotoxicity assays, the Salmonella typhimurium reverse mutation assay (Ames test), the in vitro mammalian chromosome aberration test, and the in vivo micronucleus assay. In the Ames test, SMG-10 (PEG coating, 10 nm) showed a positive mutagenic response in all the five test bacterial strains with and without metabolic activation, whereas SEI-10 (PEI coating, 10 nm) showed no mutagenesis in all tester strains regardless of metabolic activation. SMG-30 (PEG coating, 30 nm) was not mutagenic in the absence of metabolic activation, and became mutagenic in the presence of metabolic activation. In the chromosomal aberration test, no increase in the incidence of chromosomal aberrations was observed for all three IONPs. In the in vivo micronucleus test, there was no evidence of increased micronuclei frequencies for all three IONPs, indicating that they were not clastogenic in vivo. Taken together, our results demonstrated that IONPs with PEG coating exhibited mutagenic activity without chromosomal and clastogenic abnormalities, and smaller IONPs (SMG-10) had stronger mutagenic potential than larger ones (SMG-30); whereas, IONPs with SEI coating (SEI-10) were not genotoxic in all three standard genotoxicity assays. This suggests that the mutagenicity of IONPs depends on their particle size and surface coating.

Studies on the potent bacterial mutagen, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone: aqueous stability, XAD recovery and analytical determination in drinking water and in chlorinated humic acid solutions.

PubMed

Meier, J R; Knohl, R B; Coleman, W E; Ringhand, H P; Munch, J W; Kaylor, W H; Streicher, R P; Kopfler, F C

1987-12-01

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) was detected by gas chromatography/mass spectrometry in drinking water samples from 3 locations in the U.S.A., and also in a chlorinated humic acid solution. MX appears to account for a significant proportion of the mutagenicity of these samples, as measured in the Ames test using strain TA100 without metabolic activation. Studies on recovery of MX from spiked water samples by XAD-2/8 resin adsorption/acetone elution indicated that sample acidification prior to resin adsorption was essential to the effective recovery of MX. The stability of MX in aqueous solution was pH and temperature dependent. At 23 degrees C the order of stability, based on persistence of mutagenic activity was found to be: pH 2 greater than pH 4 greater than pH 8 greater than pH 6. The half-life at pH 8 and 23 degrees C was 4.6 days. One of the degradation products has been tentatively identified as 2-chloro-3-(dichloromethyl)-4-oxo-2-butenoic acid, an open form of MX which appears to be in the "E" configuration. Overall, these results suggest that MX is formed during water chlorination as a result of reaction of chlorine with humic substances, and that a substantial fraction of the MX formed is likely to persist throughout the distribution system.

Thai generic-brand dry canine foods: mutagenicity and the effects of feeding in vivo and in vitro.

PubMed

Khuntamoon, Tanyalak; Thepouyporn, Apanchanid; Kaewprasert, Sarunya; Prangthip, Pattaneeya; Pooudoung, Somchai; Chaisri, Urai; Maneesai, Phudit; Kwanbunjan, Karunee

2016-01-20

The commercial pet-food industry and the market value of the pet industry have increased. Most owners are concerned about their pets' health, and prefer commercial pet foods as their regular diet. This study thus aimed to determine whether a selection of local generic-brand dry canine foods had any potential to promote chronic disease. Five local, generic-brand, dry canine foods were studied for potential mutagenicity; the effects of long-term consumption were also observed in rats. All canine foods were extracted with distilled water and absolute ethanol. The Ames test was used to detect short-term genetic damage, using Salmonella typhimurium tester strains TA98 and TA100. Simultaneously, the long-term effects were studied in an animal model by observing rats fed with these canine foods, compared with normal rat food, for a period of 15 weeks. Using the water extracts, all dry canine foods studied showed considerable mutagenic effects on the tester strains. One brand affected both tester strains, whereas 3 showed positive to TA98, and one to TA100. With the absolute ethanol extract, three of the five brands had a considerable mutagenic effect on TA98, and another affected TA100. In the long-term test, all rats remained alive until the end of the experiment, exhibited no apparent signs of toxicity or serious illness, and maintained normal bodyweight and weight gain. Serum blood biochemistry and hematological parameters in canine food-fed rats showed some negative effects. Correspondingly, histopathological investigation of their liver and kidneys showed deterioration. Mutagenic potential and the negative potential health impacts were observed in all local-brand dry canine foods tested.

NASA Ames Environmental Sustainability Report 2011

NASA Technical Reports Server (NTRS)

Clarke, Ann H.

2011-01-01

The 2011 Ames Environmental Sustainability Report is the second in a series of reports describing the steps NASA Ames Research Center has taken toward assuring environmental sustainability in NASA Ames programs, projects, and activities. The Report highlights Center contributions toward meeting the Agency-wide goals under the 2011 NASA Strategic Sustainability Performance Program.

Evaluation of Antitrypanosomal Dihydroquinolines for Hepatotoxicity, Mutagenicity, and Methemoglobin Formation In Vitro

PubMed Central

Werbovetz, Karl A.; Riccio, Edward S.; Furimsky, Anna; Richard, Julian V.; He, Shanshan; Iyer, Lalitha; Mirsalis, Jon

2014-01-01

N 1-benzylated dihydroquinolin-6-ols and their corresponding esters display exceptional activity against African trypanosomes in vitro, and administration of members of this class of compounds to trypanosome-infected mice results in cures in a first stage African trypanosomiasis model. Since a quinone imine intermediate has been implicated in the antiparasitic mechanism of action of these compounds, evaluation of the hepatotoxic, mutagenic, and methemoglobin-promoting effects of these agents was performed. 1-Benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-ol hydrochloride (OSU-36.HCl) and 1-benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate (OSU-40) showed outstanding in vitro selectivity for T. brucei compared to the HepG2, Hep3B, Huh7 and PLC5 hepatocyte cell lines. OSU-36.HCl and 1-(2-methoxybenzyl)-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate (OSU-75) were not mutagenic when screened in the Ames assay, with or without metabolic activation. The latter two compounds promoted time- and dose-dependent formation of methemoglobin when incubated in whole human blood, but such levels were below those typically required to produce symptoms of methemoglobinemia in humans. While compounds capable of quinone imine formation require careful evaluation, these in vitro studies indicate that antitrypanosomal dihydroquinolines merit further study as drug candidates against the neglected tropical disease human African trypanosomiasis. PMID:24819520

Quantitative assessment of the dose-response of alkylating agents in DNA repair proficient and deficient ames tester strains.

PubMed

Tang, Leilei; Guérard, Melanie; Zeller, Andreas

2014-01-01

Mutagenic and clastogenic effects of some DNA damaging agents such as methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) have been demonstrated to exhibit a nonlinear or even "thresholded" dose-response in vitro and in vivo. DNA repair seems to be mainly responsible for these thresholds. To this end, we assessed several mutagenic alkylators in the Ames test with four different strains of Salmonella typhimurium: the alkyl transferases proficient strain TA1535 (Ogt+/Ada+), as well as the alkyl transferases deficient strains YG7100 (Ogt+/Ada-), YG7104 (Ogt-/Ada+) and YG7108 (Ogt-/Ada-). The known genotoxins EMS, MMS, temozolomide (TMZ), ethylnitrosourea (ENU) and methylnitrosourea (MNU) were tested in as many as 22 concentration levels. Dose-response curves were statistically fitted by the PROAST benchmark dose model and the Lutz-Lutz "hockeystick" model. These dose-response curves suggest efficient DNA-repair for lesions inflicted by all agents in strain TA1535. In the absence of Ogt, Ada is predominantly repairing methylations but not ethylations. It is concluded that the capacity of alkyl-transferases to successfully repair DNA lesions up to certain dose levels contributes to genotoxicity thresholds. Copyright © 2013 Wiley Periodicals, Inc.

The efficiency of solvent extraction of mutagenic compounds in particulates exhausted from a small diesel engine.

PubMed

Tahara, I; Kinouchi, T; Kataoka, K; Ohnishi, Y

1994-06-01

Organic materials were extracted from particulates exhausted from a small diesel engine (displacement 269 ml) by the ultrasonic extraction method with three different solvent systems, methanol, dichloromethane and a 4:1 (v:v) mixture of benzene and ethanol. These solvent-extracted materials were tested for mutagenic activity by the Ames Salmonella/microsome assay system using Salmonella typhimurium strains TA98, TA100, TA98NR and TA98/1,8-DNP6. The concentrations of 1-nitropyrene (1-NP) and 1,6-dinitropyrene (1,6-diNP) in these extracted materials were also measured after nitroreduction by high pressure liquid chromatography. The methanol-extracted and benzene-ethanol-extracted materials showed the lowest and the highest mutagenic activity, respectively. The methanol-extracted, dichloromethane-extracted and benzene-ethanol-extracted materials induced 260, 1,570 and 3,240 His+ revertants per plate per mg of extracted materials, respectively, from strain TA98 in the absence of S9 mix. These materials showed decreased mutagenicity for strains TA98NR and TA98/1,8-DNP6, indicating that the particulates in the diesel engine exhaust contained 1-NP and diNPs. Actually, the amount of 1-NP and 1,6-diNP in the methanol-extracted, dichloromethane-extracted and benzene-ethanol-extracted materials were 17.0 and 0.03 ng, 37.5 and 0.97 ng, and 71.3 and 1.03 ng per mg of extracted materials, respectively, accounting for 11.9 and 3.2%, 4.4 and 17.3%, and 4.0 and 8.9%, respectively, of the total mutagenicity of the extracted materials. From these results it is concluded that a mixture of benzene-ethanol (4:1, v/v) is the most suitable solvent for extraction of organic matter containing nitrated polycyclic aromatic hydrocarbons such as NPs from particulates in diesel engine exhaust.

Mutagenicity and cytotoxicity evaluation of photo-catalytically treated petroleum refinery wastewater using an array of bioassays.

PubMed

Iqbal, Munawar; Nisar, Jan; Adil, Muhammad; Abbas, Mazhar; Riaz, Muhammad; Tahir, M Asif; Younus, Muhammad; Shahid, Muhammad

2017-02-01

Degradation and detoxification of petroleum refinery wastewater (PRW) was carried out by advanced oxidation processes (UV/TiO 2 /H 2 O 2 and gamma radiation/H 2 O 2 ). Response surface methodology (RSM) was used to optimize the independent variables. The cytotoxicity was evaluated using Allium cepa, brime shrimp and haemolytic assays; whereas mutagenicity was tested by Ames tests (TA98 and TA100 strains). Maximum reductions in COD and BOD were recorded as 78% and 87% for UV/TiO 2 /H 2 O 2 and 77% and 86% for gamma ray/H 2 O 2 , respectively. Treatments with both methods at optimized conditions reduced the cytotoxicity and mutagenicity of PRW, however, UV/TiO 2 /H 2 O 2 system was found slightly efficient as compared to gamma ray/H 2 O 2 . From the results, it can be concluded that AOP's can successfully be utilized for the degradation of toxic pollutants in petroleum refinery wastewater. Moreover, the bioassays used in this study offered a good reliability for checking the detoxification of treated and un-treated PRW wastewater. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mutagenic activity of south Indian food items.

PubMed

Sivaswamy, S N; Balachandran, B; Balanehru, S; Sivaramakrishnan, V M

1991-08-01

Dietary components and food dishes commonly consumed in South India were screened for their mutagenic activity. Kesari powder, calamus oil, palm drink, toddy and Kewra essence were found to be strongly mutagenic; garlic, palm oil, arrack, onion and pyrolysed portions of bread toast, chicory powder were weakly mutagenic, while tamarind and turmeric were not. Certain salted, sundried and oil fried food items were also mutagenic. Cissus quadrangularis was mutagenic, while 'decoctions' of cumin seeds, aniseeds and ginger were not. Several perfumes, essential oils and colouring agents, which are commonly used were also screened and many of them exhibited their mutagenic potential by inducing the 'reverse mutation' in Salmonella typhimurium tester strains.

An Integrated View of Air Mutagenicity

EPA Science Inventory

The mutagenic potency of ambient air particulate material (PM) in the Salmonella mutagenicity assay (revertants/mg PM) varies only ~1 order of magnitude worldwide; however, the mutagenic potency of the air itself (revertants/m3 of air) varies ~5 orders of magnitude (IARC Monograp...

Mutagenicity of Cookstove Emissions

EPA Science Inventory

The presentation by David DeMarini will focus on emission factors, including mutagenicity, for 3 stoves. It will correlate the emission factors to assess the health safety of the stove systems and place the mutagenicity emission factor in context with that of other combustion em...

Chemistry and potential mutagenicity of humic substances in waters from different watersheds in Britain and Ireland

USGS Publications Warehouse

Watt, B.E.; Malcolm, R.L.; Hayes, M.H.B.; Clark, N.W.E.; Chipman, J.K.

1996-01-01

Humic substances are amorphous organic macromolecules responsible for the hue of natural waters. They are also known to be precursors of mutagens formed on chlorination prior to distribution of drinking water. In this study humic substances from the waters of primary streams, from major rivers, and from reservoirs were isolated and fractionated into humic acids (HA), fulvic acids (FA) and XAD-4 acids using columns of XAD-8 and of XAD-4 resins in tandem, and the fractions from the different sources were chlorinated and assayed for mutagenicity. CPMAS 13C NMR spectroscopy showed marked differences in compositions not only between HA, FA, and XAD-4 acids from the same water samples, but also between the same fractions from water samples from different watersheds. There were found to be strong similarities between the fractions from watersheds which had closely related soil types. Aromaticity was greatest in HAs, and lowest in XAD-4 acids, and carboxyl contents and aliphatic character were greatest in the XAD-4 acids. Carbon content decreased in the order HA > FA > XAD-4 acids, and amino acids and neutral sugars contents decreased in the order HA > XAD-4 > FA. Titration data complemented aspects of the NMR data, demonstrating that carboxyl content decreased in the order XAD-4 acids > FA > HA, and indicated that phenolic character was highest in HAs and lowest in the XAD-4 acids. All samples tested gave rise to bacterial mutagens on chlorination. Although the mutagenicities were of the same order of magnitude for the chlorinated humic samples from the different sources, the samples which showed the greatest number of revertant bacterial colonies were from the Thames and Trent, large rivers with humic materials from diverse environments, and relatively high in amino acid contents.

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

PubMed Central

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

Rat liver endothelial and Kupffer cell-mediated mutagenicity and polycyclic aromatic hydrocarbons and aflatoxin B sub 1

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

Steinberg, P.; Schlemper, B.; Molitor, E.

The ability of isolated rat liver endothelial and Kupffer cells to activate benzo(a)pyrene (BP), trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (DDBP), trans-1,2-dihydroxy-1,2-dihydrochrysene (DDCH), and aflatoxin B{sub 1} (AFB{sub 1}) to mutagenic metabolites was assessed by means of a cell-mediated bacterial mutagenicity assay and compared with the ability of parenchymal cells to activate these compounds. Endothelial and Kupffer cells from untreated rats were able to activate AFB{sub 1} and DDBP; DDBP was activated even in the absence of an NADPH-generating system. Pretreating the animals with Aroclor 1254 strongly enhanced the mutagenicity of the dihydrodiol, whereas the mutagenicity of AFB{sub 1} showed a slight increase. BP andmore » DDCH were only activated by endothelial and Kupffer cells isolated from Aroclor 1254-pretreated rats. Parenchymal cells form untreated animals activated all four carcinogens tested; Aroclor 1254 enhanced the parenchymal cell-mediated mutagenicity of BP and DDCH but did not affect that of DDBP and clearly reduced that of AFB{sub 1}. The reduced mutagenicity of AFB{sub 1} correlates with the decrease in the amount of 2{alpha}-hydroxytestosterone formed when testosterone was incubated with parenchymal cell microsomes from Aroclor 1254-pretreated rats (compared with microsomes from untreated animals): the formation of 2{alpha}-hydroxytestosterone is specifically catalyzed by cytochrome P-450h, a hemoprotein thought to be involved in the activation of AFB{sub 1}. These results show that not only rat liver parenchymal cells, but also endothelial and Kupffer cells, activated several carcinogens to mutagenic metabolites.« less

NASA Ames Research Center Overview

NASA Technical Reports Server (NTRS)

Boyd, Jack

2006-01-01

A general overview of the NASA Ames Research Center is presented. The topics include: 1) First Century of Flight, 1903-2003; 2) NACA Research Centers; 3) 65 Years of Innovation; 4) Ames Projects; 5) NASA Ames Research Center Today-founded; 6) Astrobiology; 7) SOFIA; 8) To Explore the Universe and Search for Life: Kepler: The Search for Habitable Planets; 9) Crew Exploration Vehicle/Crew Launch Vehicle; 10) Lunar Crater Observation and Sensing Satellite (LCROSS); 11) Thermal Protection Materials and Arc-Jet Facility; 12) Information Science & Technology; 13) Project Columbia Integration and Installation; 14) Air Traffic Management/Air Traffic Control; and 15) New Models-UARC.

Ames Lab 101: Lanthanum Decanting

ScienceCinema

Riedemann, Trevor

2018-04-27

Ames Laboratory scientist Trevor Riedemann explains the process that allows Ames Laboratory to produce some of the purest lanthanum in the world. This and other high-purity rare-earth elements are used to create alloys used in various research projects and play a crucial role in the Planck satellite mission.

Ames Lab 101: Rare Earths

ScienceCinema

Gschneidner, Karl

2017-12-11

"Mr. Rare Earth," Ames Laboratory scientist Karl Gschneidner Jr., explains the importance of rare-earth materials in many of the technologies we use today -- ranging from computers to hybrid cars to wind turbines. Gschneidner is a world renowned rare-earths expert at the U.S. Department of Energy's Ames Laboratory.

In vivo formation of mutagens by intraperitoneal administration of polycyclic aromatic hydrocarbons in animals during exposure to nitrogen dioxide.

PubMed

Miyanishi, K; Kinouchi, T; Kataoka, K; Kanoh, T; Ohnishi, Y

1996-07-01

Consumption of fossil fuels has increased indoor and outdoor concentrations of polycyclic aromatic hydrocarbons (PAHs) and nitrogen dioxide (NO2). To study the combined effect of PAH administration and NO2 exposure on mutagenicity of urine from animals we injected 400 mg/kg body wt i.p. one of five kinds of PAH (pyrene, fluoranthene, fluorene, anthracene and chrysene) into ICR mice, Wistar rats, Syrian golden hamsters or Hartley guinea pigs after exposure to 20 p.p.m. NO2 gas for 24 h and then exposed the animals to NO2 gas for an additional 24 h. During the latter 24 h we collected the urine and assayed its mutagenicity with the Ames Salmonella strains after treatment with beta-glucuronidase and arylsulfatase and extraction with dichloromethane. The urine from mice treated with both PAH and NO2 showed high mutagenicity for Salmonella typhimurium strains TA98 and TA100, whereas the urine from mice treated with PAH and air showed almost no mutagenic activity. The mutagenicity was decreased in nitroreductase- and acetyltransferase-deficient strains TA98NR and TA98/1,8-DNP6 respectively. Treatment with a mixture of 20% of each of the five kinds of PAH and NO2 augmented the urinary mutagenicity of mice 1.5-fold. The urine from hamsters treated with pyrene or fluoranthene and NO2 was also highly mutagenic, but that from rats or guinea pigs was not very mutagenic. The mutagenicity was also decreased in strains TA98NR and TA98/1,8-DNP6. These results suggest that the urine contains nitro compounds and that the nitration of PAHs occurs in the body of animals under exposure to NO2 gas. Actually, the nitrated metabolites of pyrene, 1-nitro-6/8-hydroxypyrene and 1-nitro-3-hydroxypyrene, were detected in the urine from mice treated with pyrene under exposure to NO2 gas. To elucidate the mechanism of in vivo nitration, NO2 (20 p.p.m.) was bubbled through 50 mM Tris-HCl buffer (pH 7.4) or dichloromethane solution containing pyrene or 1-hydroxypyrene (10 microg/ml). Pyrene was

Formation of mutagens in cooked foods. I. Beef.

PubMed

Spingarn, N E; Weisburger, J H

1979-09-01

Mutagens detectable by Salmonella typhimurium TA98, after activation by liver S-9 fraction, are formed when meat is cooked by frying, broiling and boiling. High levels of mutagenic activity are formed rapidly when frying, or more slowly during broiling. Formation of mutagens in boiled beef stock requires several days under reflux, but shows a strong concentration dependence. Time curves suggest that a period exists during which mutagens are not readily formed; however, after this period mutagen production is rapid. Hamburgers from commercial franchises were frequently mutagenically active.

Evaluation of Antitrypanosomal Dihydroquinolines for Hepatotoxicity, Mutagenicity, and Methemoglobin Formation In Vitro.

PubMed

Werbovetz, Karl A; Riccio, Edward S; Furimsky, Anna; Richard, Julian V; He, Shanshan; Iyer, Lalitha; Mirsalis, Jon

2014-07-01

N1-Benzylated dihydroquinolin-6-ols and their corresponding esters display exceptional activity against African trypanosomes in vitro, and administration of members of this class of compounds to trypanosome-infected mice results in cures in a first-stage African trypanosomiasis model. Since a quinone imine intermediate has been implicated in the antiparasitic mechanism of action of these compounds, evaluation of the hepatotoxic, mutagenic, and methemoglobin-promoting effects of these agents was performed. 1-Benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-ol hydrochloride and 1-benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate showed outstanding in vitro selectivity for Trypanosoma brucei compared to the HepG2, Hep3B, Huh7, and PLC5 hepatocyte cell lines. 1-Benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-ol hydrochloride and 1-(2-methoxybenzyl)-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate were not mutagenic when screened in the Ames assay, with or without metabolic activation. The latter 2 compounds promoted time- and dose-dependent formation of methemoglobin when incubated in whole human blood, but such levels were below those typically required to produce symptoms of methemoglobinemia in humans. Although compounds capable of quinone imine formation require careful evaluation, these in vitro studies indicate that antitrypanosomal dihydroquinolines merit further study as drug candidates against the neglected tropical disease human African trypanosomiasis. © The Author(s) 2014.

NASA Ames Research Center: An Overview

NASA Technical Reports Server (NTRS)

Tu, Eugene; Yan, Jerry Chi Yiu

2017-01-01

This overview of NASA Ames Research Center is intended to give the target audience of university students a general understanding of the mission, core competencies, and research goals of NASA and Ames.

Tiger Team Assessment of the Ames Laboratory

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

Not Available

1992-03-01

This report documents the Tiger Assessment of the Ames Laboratory (Ames), located in Ames, Iowa. Ames is operated for the US Department of Energy (DOE) by Iowa State University. The assessment was conducted from February 10 to March 5, 1992, under the auspices of the Office of Special Projects, Office of the Assistant Secretary of Environment, Safety and Health, Headquarters, DOE. The assessment was comprehensive, encompassing Environment, Safety, and Health (ES H) disciplines; management practices; and contractor and DOE self-assessments. Compliance with applicable Federal, State of Iowa, and local regulations; applicable DOE Orders; best management practices; and internal requirements atmore » Ames Laboratory were assessed. In addition, an evaluation of the adequacy and effectiveness of DOE and the site contractor's management of ES H/quality assurance program was conducted.« less

Occurrence of mutagens in canned foods.

PubMed

Krone, C A; Iwaoka, W T

1984-01-01

Mutagens are shown to be present in a variety of commercially heat-processed foods. Since these substances are not present in the unheated raw material, it appears that they are produced during processing. Canned salmon and beef broth showed the highest mutagenicity while other canned beef and fish products yielded lower but detectable levels. These findings are significant not only because of the large proportion of the food supply which is processed by canning, but also because the mutagens in these foods exhibit chemical behaviors and Salmonella strain specificity similar to mutagens in grilled foods which have been shown to be mammalian carcinogens.

Crude cacao Theobroma cacao extract reduces mutagenicity induced by benzo[a]pyrene through inhibition of CYP1A activity in vitro.

PubMed

Ohno, Marumi; Sakamoto, Kentaro Q; Ishizuka, Mayumi; Fujita, Shoichi

2009-08-01

Polyphenols have been shown to have potent antioxidant activity, and therefore, food containing polyphenols is expected to contribute to the prevention of cancer. However, food contains not only polyphenols but also various other constituents. We used the Ames test to investigate the effects of crude extracts of whole cacao products, which are known to be rich in polyphenols, on the mutagenicity of benzo[a]pyrene (B[a]P) in Salmonella typhimurium strain TA 98 and tert-butyl hydroperoxide (t-BuOOH) in S. typhimurium strain TA 102. B[a]P induces mutagenicity by metabolic activation and t-BuOOH induces it by generation of free radicals. While white chocolate did not modulate the numbers of revertant colonies produced by B[a]P treatment, milk chocolate and cacao powder extracts did. On the other hand, surprisingly, none of the cacao products tested affected the number of revertant colonies when t-BuOOH was used as the mutagen. At maximum concentration (13.25 mg cacao powder/ml), the crude cacao powder extract reduced ethoxyresorufin O-deethylase activity to 17.4% of the control, suggesting that whole cacao products inhibit cytochrome P450 (CYP) 1A activity. In conclusion, inhibition of CYP1A activity by cacao products may prevent DNA damage by reducing metabolic activation of carcinogens. Copyright 2009 John Wiley & Sons, Ltd.

Autonomy @ Ames

NASA Technical Reports Server (NTRS)

Van Dalsem, William; Krishnakumar, Kalmanje Srinivas

2016-01-01

This is a powerpoint presentation that highlights autonomy across the 15 NASA technology roadmaps, including specific examples of projects (past and present) at NASA Ames Research Center. The NASA technology roadmaps are located here: http:www.nasa.govofficesocthomeroadmapsindex.html

Chemistry of mutagens and carcinogens in broiled food.

PubMed Central

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

2017 Solar Eclipse, Ames Research Center

NASA Image and Video Library

2017-08-21

Taking a break from their duties at the Ames Vertical Gun Range to look up at the eclipse over Ames Research Center in Mountain View are from left to right are Alfredo "Freddie" Perez, Chuck Cornelison, Don Bowling, Adam Parish

NASA Ames 2016 Highlights

NASA Image and Video Library

2016-12-28

2016 presented the opportunity for NASA's Ames Research Center to meet its challenges and opportunities head on. Projects ranged from testing the next generation of air traffic control software to studying the stars of our galaxy. From developing life science experiments that flew aboard the International Space Station to helping protect our planet through airborne Earth observation campaigns. NASA's missions and programs are challenging and the people at NASA Ames Research Center continue to reach new heights and reveal the unknown for the benefit of all humankind!

Mutagenicity of fume particles from stainless steel welding.

PubMed

Hedenstedt, A; Jenssen, D; Lidestein B-M; Ramel, C; Rannug, U; Stern, R M

1977-12-01

Welding fume particles collected from different welding procedures were tested for mutagenicity in Escherichia coli, with the inhibition zone in pol A- as compared to pol A+, and in Salmonella typhimurium, TA 100 strain. While no mutagenicity was found with mild steel welding, a mutagenic effect was established with samples from stainless steel welding. This mutagenicity was particularly associated with manual metal arc (MMA) welding, and less so with metal inert-gas welding. A decrease in or an elimination of the effect occurred with a liver microsomal metabolizing system (S-9 mix). The MMA samples produced the strongest mutagenic effect. More-detailed investigations on these samples showed that the mutagenic agent(s) is water soluble. An increased mutagenicity, which also revealed the induction of frame shift mutations, was found with TA 98. The same welding fume sample was used for a mutagenicity test (resistance to 6-thioguanine) with V 79 hamster cells. Because of the high toxicity of these welding fume particles on the cells, only very low concentrations could be tested, but the increase of mutations, when compared to the negative control, was significant. It is suggested that hexavalent chromium may be involved in the mutagenic effect of the welding fumes.

Ames Life Science Data Archive: Translational Rodent Research at Ames

NASA Technical Reports Server (NTRS)

Wood, Alan E.; French, Alison J.; Ngaotheppitak, Ratana; Leung, Dorothy M.; Vargas, Roxana S.; Maese, Chris; Stewart, Helen

2014-01-01

The Life Science Data Archive (LSDA) office at Ames is responsible for collecting, curating, distributing and maintaining information pertaining to animal and plant experiments conducted in low earth orbit aboard various space vehicles from 1965 to present. The LSDA will soon be archiving data and tissues samples collected on the next generation of commercial vehicles; e.g., SpaceX & Cygnus Commercial Cargo Craft. To date over 375 rodent flight experiments with translational application have been archived by the Ames LSDA office. This knowledge base of fundamental research can be used to understand mechanisms that affect higher organisms in microgravity and help define additional research whose results could lead the way to closing gaps identified by the Human Research Program (HRP). This poster will highlight Ames contribution to the existing knowledge base and how the LSDA can be a resource to help answer the questions surrounding human health in long duration space exploration. In addition, it will illustrate how this body of knowledge was utilized to further our understanding of how space flight affects the human system and the ability to develop countermeasures that negate the deleterious effects of space flight. The Ames Life Sciences Data Archive (ALSDA) includes current descriptions of over 700 experiments conducted aboard the Shuttle, International Space Station (ISS), NASA/MIR, Bion/Cosmos, Gemini, Biosatellites, Apollo, Skylab, Russian Foton, and ground bed rest studies. Research areas cover Behavior and Performance, Bone and Calcium Physiology, Cardiovascular Physiology, Cell and Molecular Biology, Chronobiology, Developmental Biology, Endocrinology, Environmental Monitoring, Gastrointestinal Physiology, Hematology, Immunology, Life Support System, Metabolism and Nutrition, Microbiology, Muscle Physiology, Neurophysiology, Pharmacology, Plant Biology, Pulmonary Physiology, Radiation Biology, Renal, Fluid and Electrolyte Physiology, and Toxicology. These

THE MUTAGENICITY OF METALLIZED AND UNMETALLIZED AZO AND FORMAZAN DYES IN THE SALMONELLA MUTAGENICITY ASSAY

EPA Science Inventory

The mutagenicity of metallized and unmetallized azo and formazan dyes in the Salmonella mutagenicity
Laura. C. Edwards', Harold S. Freeman'*, and Larry D. Claxton2

Abstract
In previous papers, the synthesis and chemical properties of iron complexed azo and formazan d...

Two dechlorinated chlordecone derivatives formed by in situ chemical reduction are devoid of genotoxicity and mutagenicity and have lower proangiogenic properties compared to the parent compound.

PubMed

Legeay, Samuel; Billat, Pierre-André; Clere, Nicolas; Nesslany, Fabrice; Bristeau, Sébastien; Faure, Sébastien; Mouvet, Christophe

2018-05-01

Chlordecone (CLD) is a chlorinated hydrocarbon insecticide, now classified as a persistent organic pollutant. Several studies have previously reported that chronic exposure to CLD leads to hepatotoxicity, neurotoxicity, raises early child development and pregnancy complications, and increases the risk of liver and prostate cancer. In situ chemical reduction (ISCR) has been identified as a possible way for the remediation of soils contaminated by CLD. In the present study, the objectives were (i) to evaluate the genotoxicity and the mutagenicity of two CLD metabolites formed by ISCR, CLD-5a-hydro, or CLD-5-hydro (5a- or 5- according to CAS nomenclature; CLD-1Cl) and tri-hydroCLD (CLD-3Cl), and (ii) to explore the angiogenic properties of these molecules. Mutagenicity and genotoxicity were investigated using the Ames's technique on Salmonella typhimurium and the in vitro micronucleus micromethod with TK6 human lymphoblastoid cells. The proangiogenic properties were evaluated on the in vitro capillary network formation of human primary endothelial cells. Like CLD, the dechlorinated derivatives of CLD studied were devoid of genotoxic and mutagenic activity. In the assay targeting angiogenic properties, significantly lower microvessel lengths formed by endothelial cells were observed for the CLD-3Cl-treated cells compared to the CLD-treated cells for two of the three tested concentrations. These results suggest that dechlorinated CLD derivatives are devoid of mutagenicity and genotoxicity and have lower proangiogenic properties than CLD.

76 FR 22900 - Decision To Evaluate a Petition To Designate a Class of Employees From Ames Laboratory in Ames...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-25

... as follows: Facility: Ames Laboratory. Location: Ames, Iowa. Job Titles and/or Job Duties: All.... FOR FURTHER INFORMATION CONTACT: Stuart L. Hinnefeld, Director, Division of Compensation Analysis and...

2017 Solar Eclipse, Ames Research Center

NASA Image and Video Library

2017-08-21

Taking a break from his duties at the Ames Vertical Gun Range to look up at the eclipse over Ames Research Center in Mountain View Adam Parrish not only views but wears, on his forehead, the image of the 2017 Solar eclipse at 09:20:56 on August 21, 2017.

Sister chromatid exchanges induced by inhaled anesthetics

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

White,A.E.; Takehisa, S.; Eger II, E.I.

1970-05-01

There is sufficient evidence that anesthetics may cause cancer to justify a test of their carcinogenic potential. Baden et al., using the Ames test, a rapid and inexpensive genetic indicator of carcinogenicity, have shown that among currently used anesthetics fluorxene alone caused bacterial mutations. The authors used the sister chromatid exchange (SCE) technique, another rapid assay of mutagenic-carcinogenic potential. The frequency of sister chromatid exchanges in Chinese hamster ovary cells increases when the cell cultures are exposed to mutagen-carcinogens, particulary in the presence of a metabolic activating system. With this test system a one-hour exposure to 1 MAC nitrous oxide,more » diethyl ether, trichloroethylene, halothane, enflurane, isoflurane, methoxyflurane, or chloroform did not increase SCE values. Divinyl ether, fluroxene and ethyl vinyl ether increased SCE values in the same circumstances. Results of this study of mammalian cells suggest that no currently used anesthetic is a mutagen-carcinogen. The results also suggest that anesthetics containing a vinyl moiety may be mutagen-carcinogens.« less

The State-of-Play of Anomalous Microwave Emission (AME) research

NASA Astrophysics Data System (ADS)

Dickinson, Clive; Ali-Haïmoud, Y.; Barr, A.; Battistelli, E. S.; Bell, A.; Bernstein, L.; Casassus, S.; Cleary, K.; Draine, B. T.; Génova-Santos, R.; Harper, S. E.; Hensley, B.; Hill-Valler, J.; Hoang, Thiem; Israel, F. P.; Jew, L.; Lazarian, A.; Leahy, J. P.; Leech, J.; López-Caraballo, C. H.; McDonald, I.; Murphy, E. J.; Onaka, T.; Paladini, R.; Peel, M. W.; Perrott, Y.; Poidevin, F.; Readhead, A. C. S.; Rubiño-Martín, J.-A.; Taylor, A. C.; Tibbs, C. T.; Todorović, M.; Vidal, Matias

2018-02-01

Anomalous Microwave Emission (AME) is a component of diffuse Galactic radiation observed at frequencies in the range ≈ 10-60 GHz. AME was first detected in 1996 and recognised as an additional component of emission in 1997. Since then, AME has been observed by a range of experiments and in a variety of environments. AME is spatially correlated with far-IR thermal dust emission but cannot be explained by synchrotron or free-free emission mechanisms, and is far in excess of the emission contributed by thermal dust emission with the power-law opacity consistent with the observed emission at sub-mm wavelengths. Polarization observations have shown that AME is very weakly polarized ( ≲ 1 %). The most natural explanation for AME is rotational emission from ultra-small dust grains ("spinning dust"), first postulated in 1957. Magnetic dipole radiation from thermal fluctuations in the magnetization of magnetic grain materials may also be contributing to the AME, particularly at higher frequencies ( ≳ 50 GHz). AME is also an important foreground for Cosmic Microwave Background analyses. This paper presents a review and the current state-of-play in AME research, which was discussed in an AME workshop held at ESTEC, The Netherlands, June 2016.

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

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

De Flora, Silvio, E-mail: sdf@unige.it

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

Fine and ultrafine atmospheric particulate matter at a multi-influenced urban site: Physicochemical characterization, mutagenicity and cytotoxicity.

PubMed

Landkocz, Yann; Ledoux, Frédéric; André, Véronique; Cazier, Fabrice; Genevray, Paul; Dewaele, Dorothée; Martin, Perrine J; Lepers, Capucine; Verdin, Anthony; Courcot, Lucie; Boushina, Saâd; Sichel, François; Gualtieri, Maurizio; Shirali, Pirouz; Courcot, Dominique; Billet, Sylvain

2017-02-01

Particulate Matter (PM) air pollution is one of the major concerns for environment and health. Understanding the heterogeneity and complexity of fine and ultrafine PM is a fundamental issue notably for the assessment of PM toxicological effects. The aim of this study was to evaluate mutagenicity and cytotoxicity of a multi-influenced urban site PM, with or without the ultrafine fraction. For this purpose, PM 2.5-0.3 (PM with aerodynamic diameter ranging from 0.3 to 2.5 μm) and PM 2.5 were collected in Dunkerque, a French coastal industrial city and were extensively characterized for their physico-chemical properties, including inorganic and organic species. In order to identify the possible sources of atmospheric pollution, specific criteria like Carbon Preference Index (CPI) and PAH characteristic ratios were investigated. Mutagenicity assays using Ames test with TA98, TA102 and YG1041 Salmonella strains with or without S9 activation were performed on native PM sample and PM organic extracts and water-soluble fractions. BEAS-2B cell viability and cell proliferation were evaluated measuring lactate dehydrogenase release and mitochondrial dehydrogenase activity after exposure to PM and their extracts. Several contributing sources were identified in PM: soil resuspension, marine emissions including sea-salt or shipping, road traffic and industrial activities, mainly related to steelmaking or petro-chemistry. Mutagenicity of PM was evidenced, especially for PM 2.5 , including ultrafine fraction, in relation to PAHs content and possibly nitro-aromatics compounds. PM induced cytotoxic effects at relatively high doses, while alteration of proliferation with low PM doses could be related to underlying mechanisms such as genotoxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Genotoxicity assessment of propyl thiosulfinate oxide, an organosulfur compound from Allium extract, intended to food active packaging.

PubMed

Mellado-García, P; Maisanaba, S; Puerto, M; Llana-Ruiz-Cabello, M; Prieto, A I; Marcos, R; Pichardo, S; Cameán, A M

2015-12-01

Essential oils from onion (Allium cepa L.), garlic (Allium sativum L.), and their main components, such as propyl thiosulfinate oxide (PTSO) are being intended for active packaging with the purpose of maintaining and extending food product quality and shelf life. The present work aims to assess for the first time the potential mutagenicity/genotoxicity of PTSO (0-50 µM) using the following battery of genotoxicity tests: (1) the bacterial reverse-mutation assay in Salmonella typhimurium (Ames test, OECD 471); (2) the micronucleus test (OECD 487) (MN) and (3) the mouse lymphoma thymidine-kinase assay (OECD 476) (MLA) on L5178YTk(+/-), cells; and (4) the comet assay (with and without Endo III and FPG enzymes) on Caco-2 cells. The results revealed that PTSO was not mutagenic in the Ames test, however it was mutagenic in the MLA assay after 24 h of treatment (2.5-20 µM). The parent compound did not induce MN on mammalian cells; however, its metabolites (in the presence S9) produced positive results (from 15 µM). Data from the comet assay indicated that PTSO did not induce DNA breaks or oxidative DNA damage. Further in vivo genotoxicity tests are needed to confirm its safety before it is used as active additive in food packaging. Copyright © 2015 Elsevier Ltd. All rights reserved.

CHARACTERIZATION OF AUTOMOTIVE EMISSIONS BY BACTERIAL MUTAGENESIS BIOASSAY: A REVIEW

EPA Science Inventory

Due to the growing numbers of diesel passenger automobiles in the United States, there has been an expanded effort to understand the health effects of airborne pollutants arising from increased automotive emissions. Bacterial mutagenicity testing has played an important role in t...

Analysis of commercial bouillons for trace levels of mutagens.

PubMed

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.

Alcohol mixed with energy drink (AMED): A critical review and meta-analysis.

PubMed

Verster, Joris C; Benson, Sarah; Johnson, Sean J; Alford, Chris; Godefroy, Samuel Benrejeb; Scholey, Andrew

2018-03-01

The purpose of this systematic review and meta-analysis was to critically review the (1) prevalence of alcohol mixed with energy drink (AMED) consumption, (2) motives for AMED consumption, (3) correlates of AMED consumption, and (4) whether AMED consumption has an impact on (a) alcohol consumption, (b) subjective intoxication, and (c) risk-taking behavior. Overall a minority of the population consumes AMED, typically infrequently. Motives for AMED consumption are predominantly hedonistic and social. Meta-analyses revealed that AMED consumers drink significantly more alcohol than alcohol-only (AO) consumers. Within-subject comparisons restricted to AMED consumers revealed that alcohol consumption does not significantly differ between typical AMED and AO occasions. On past month heaviest drinking occasions, AMED users consume significantly less alcohol on AMED occasions when compared to AO occasions. AMED consumers experience significantly fewer negative consequences and risk-taking behavior on AMED occasions compared with AO occasions. Meta-analyses of subjective intoxication studies suggest that AMED consumption does not differentially affect subjective intoxication when compared to AO consumption. In conclusion, when compared to AO consumption, mixing alcohol with energy drink does not affect subjective intoxication and seems unlikely to increase total alcohol consumption, associated risk-taking behavior, nor other negative alcohol-related consequences. Further research may be necessary to fully reveal the effects of AMED. © 2018 The Authors Human Psychopharmacology: Clinical and Experimental Published by John Wiley & Sons Ltd.

Alcohol mixed with energy drink (AMED): A critical review and meta‐analysis

PubMed Central

Benson, Sarah; Johnson, Sean J.; Alford, Chris; Godefroy, Samuel Benrejeb; Scholey, Andrew

2018-01-01

Abstract The purpose of this systematic review and meta‐analysis was to critically review the (1) prevalence of alcohol mixed with energy drink (AMED) consumption, (2) motives for AMED consumption, (3) correlates of AMED consumption, and (4) whether AMED consumption has an impact on (a) alcohol consumption, (b) subjective intoxication, and (c) risk‐taking behavior. Overall a minority of the population consumes AMED, typically infrequently. Motives for AMED consumption are predominantly hedonistic and social. Meta‐analyses revealed that AMED consumers drink significantly more alcohol than alcohol‐only (AO) consumers. Within‐subject comparisons restricted to AMED consumers revealed that alcohol consumption does not significantly differ between typical AMED and AO occasions. On past month heaviest drinking occasions, AMED users consume significantly less alcohol on AMED occasions when compared to AO occasions. AMED consumers experience significantly fewer negative consequences and risk‐taking behavior on AMED occasions compared with AO occasions. Meta‐analyses of subjective intoxication studies suggest that AMED consumption does not differentially affect subjective intoxication when compared to AO consumption. In conclusion, when compared to AO consumption, mixing alcohol with energy drink does not affect subjective intoxication and seems unlikely to increase total alcohol consumption, associated risk‐taking behavior, nor other negative alcohol‐related consequences. Further research may be necessary to fully reveal the effects of AMED. PMID:29417616

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

PubMed

De Flora, Silvio; Camoirano, Anna; Micale, Rosanna T; La Maestra, Sebastiano; Savarino, Vincenzo; Zentilin, Patrizia; Marabotto, Elisa; Suh, Mina; Proctor, Deborah M

2016-09-01

Evaluation of the reducing capacity of human gastric fluid from healthy individuals, under fasted and fed conditions, is critical for assessing the cancer hazard posed by ingested hexavalent chromium [Cr(VI)] and for developing quantitative physiologically-based pharmacokinetic models used in risk assessment. In the present study, the patterns of Cr(VI) reduction were evaluated in 16 paired pre- and post-meal gastric fluid samples collected from 8 healthy volunteers. Human gastric fluid was effective both in reducing Cr(VI), as measured by using the s-diphenylcarbazide colorimetric method, and in attenuating mutagenicity in the Ames test. The mean (±SE) Cr(VI)-reducing ability of post-meal samples (20.4±2.6μgCr(VI)/mL gastric fluid) was significantly higher than that of pre-meal samples (10.2±2.3μgCr(VI)/mL gastric fluid). When using the mutagenicity assay, the decrease of mutagenicity produced by pre-meal and post-meal samples corresponded to reduction of 13.3±1.9 and 25.6±2.8μgCr(VI)/mL gastric fluid, respectively. These data are comparable to parallel results conducted by using speciated isotope dilution mass spectrometry. Cr(VI) reduction was rapid, with >70% of total reduction occurring within 1min and 98% of reduction is achieved within 30min with post-meal gastric fluid at pH2.0. pH dependence was observed with decreasing Cr(VI) reducing capacity at higher pH. Attenuation of the mutagenic response is consistent with the lack of DNA damage observed in the gastrointestinal tract of rodents following administration of ≤180ppm Cr(VI) for up to 90days in drinking water. Quantifying Cr(VI) reduction kinetics in the human gastrointestinal tract is necessary for assessing the potential hazards posed by Cr(VI) in drinking water. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Occurrence of Penicillium brocae and Penicillium citreonigrum, which Produce a Mutagenic Metabolite and a Mycotoxin Citreoviridin, Respectively, in Selected Commercially Available Rice Grains in Thailand.

PubMed

Shiratori, Nozomi; Kobayashi, Naoki; Tulayakul, Phitsanu; Sugiura, Yoshitsugu; Takino, Masahiko; Endo, Osamu; Sugita-Konishi, Yoshiko

2017-06-15

Commercially available rice grains in Thailand were examined to isolate the monoverticillate Penicillium species responsible for toxic yellowed rice. Penicillium species were obtained from seven out of 10 rice samples tested. Among them, one Penicillium citreonigrum isolate and six Penicillium brocae isolates were morphologically identified. The P. citreonigrum isolate produced the mycotoxin citreoviridin on a yeast extract sucrose broth medium. Mycotoxin surveys showed that citreoviridin was not detected in any samples, but one out of 10 rice samples tested was positive for aflatoxin B₁ at a level of 5.9 μg/kg. An Ames test revealed that methanol extracts from rice grains inoculated with selected P. brocae isolates were positive for strains TA100 and YG7108 of Salmonella typhimurium , suggesting the presence of base-pair substitution and DNA alkylation mutagens. Our data obtained here demonstrated that aflatoxin B₁ and toxic P. citreonigrum were present on domestic rice grains in Thailand, although limited samples were tested. Penicillium brocae , which may produce mutagenic metabolites, was isolated for the first time from the surface of Thai rice grains.

Occurrence of Penicillium brocae and Penicillium citreonigrum, which Produce a Mutagenic Metabolite and a Mycotoxin Citreoviridin, Respectively, in Selected Commercially Available Rice Grains in Thailand

PubMed Central

Shiratori, Nozomi; Kobayashi, Naoki; Tulayakul, Phitsanu; Sugiura, Yoshitsugu; Takino, Masahiko; Endo, Osamu; Sugita-Konishi, Yoshiko

2017-01-01

Commercially available rice grains in Thailand were examined to isolate the monoverticillate Penicillium species responsible for toxic yellowed rice. Penicillium species were obtained from seven out of 10 rice samples tested. Among them, one Penicillium citreonigrum isolate and six Penicillium brocae isolates were morphologically identified. The P. citreonigrum isolate produced the mycotoxin citreoviridin on a yeast extract sucrose broth medium. Mycotoxin surveys showed that citreoviridin was not detected in any samples, but one out of 10 rice samples tested was positive for aflatoxin B1 at a level of 5.9 μg/kg. An Ames test revealed that methanol extracts from rice grains inoculated with selected P. brocae isolates were positive for strains TA100 and YG7108 of Salmonella typhimurium, suggesting the presence of base-pair substitution and DNA alkylation mutagens. Our data obtained here demonstrated that aflatoxin B1 and toxic P. citreonigrum were present on domestic rice grains in Thailand, although limited samples were tested. Penicillium brocae, which may produce mutagenic metabolites, was isolated for the first time from the surface of Thai rice grains. PMID:28617318

A comparison of methods for concentrating mutagens in drinking water--recovery aspects and their implications for the chemical character of major unidentified mutagens.

PubMed

Wigilius, B; Borén, H; Carlberg, G E; Grimvall, A; Möller, M

1985-12-01

A comparison of techniques for concentrating mutagenic compounds in drinking water has shown that XAD-2 adsorption and dichloromethane extraction have acceptable and almost identical enrichment properties, while purging at an elevated temperature is inappropriate in this context. Quantitatively, the most important drinking water mutagens could only be adsorbed (extracted) after acidification of the water, and even then recovery was far from complete. Recovery experiments with known mutagens from pulp mill effluents have shown that none of the major chlorination-stage mutagens identified thus far can explain the mutagenic activity of extracts from neutral or acidified chlorinated drinking water.

Ames Research Center Research and Technology 2000

NASA Technical Reports Server (NTRS)

2002-01-01

This report highlights the challenging work accomplished during fiscal year 2000 by Ames research scientists,engineers, and technologists. It discusses research and technologies that enable the Information Age, that expand the frontiers of knowledge for aeronautics and space, and that help to maintain U.S. leadership in aeronautics and space research and technology development. The accomplishments are grouped into four categories based on four of NASA's Strategic Enterprises: Aerospace Technology, Space Science, Biological and Physical Research, and Earth Science. The primary purpose of this report is to communicate knowledge-to inform our stakeholders, customer, and partners, and the people of the United States about the scope and diversity of Ames' mission,the nature of Ames' research and technolog) activities,and the stimulating challenges ahead. The accomplishments cited illustrate the contributions that Ames is willing to improve the quality of life for our citizens and the economic position of the United States in the world marketplace.

Computational Methods Development at Ames

NASA Technical Reports Server (NTRS)

Kwak, Dochan; Smith, Charles A. (Technical Monitor)

1998-01-01

This viewgraph presentation outlines the development at Ames Research Center of advanced computational methods to provide appropriate fidelity computational analysis/design capabilities. Current thrusts of the Ames research include: 1) methods to enhance/accelerate viscous flow simulation procedures, and the development of hybrid/polyhedral-grid procedures for viscous flow; 2) the development of real time transonic flow simulation procedures for a production wind tunnel, and intelligent data management technology; and 3) the validation of methods and the flow physics study gives historical precedents to above research, and speculates on its future course.

Combusting vegetable oils in diesel engines: the impact of unsaturated fatty acids on particle emissions and mutagenic effects of the exhaust.

PubMed

Bünger, Jürgen; Bünger, Jörn F; Krahl, Jürgen; Munack, Axel; Schröder, Olaf; Brüning, Thomas; Hallier, Ernst; Westphal, Götz A

2016-06-01

High particle emissions and strong mutagenic effects were observed after combustion of vegetable oil in diesel engines. This study tested the hypothesis that these results are affected by the amount of unsaturated or polyunsaturated fatty acids of vegetable oils. Four different vegetable oils (coconut oil, CO; linseed oil, LO; palm tree oil, PO; and rapeseed oil, RO) and common diesel fuel (DF) were combusted in a heavy-duty diesel engine. The exhausts were investigated for particle emissions and mutagenic effects in direct comparison with emissions of DF. The engine was operated using the European Stationary Cycle. Particle masses were measured gravimetrically while mutagenicity was determined using the bacterial reverse mutation assay with tester strains TA98 and TA100. Combustion of LO caused the largest amount of total particulate matter (TPM). In comparison with DF, it particularly raised the soluble organic fraction (SOF). RO presented second highest TPM and SOF, followed by CO and PO, which were scarcely above DF. RO revealed the highest number of mutations of the vegetable oils closely followed by LO. PO was less mutagenic, but still induced stronger effects than DF. While TPM and SOF were strongly correlated with the content of polyunsaturated fatty acids in the vegetable oils, mutagenicity had a significant correlation with the amount of total unsaturated fatty acids. This study supports the hypothesis that numbers of double bounds in unsaturated fatty acids of vegetable oils combusted in diesel engines influence the amount of emitted particles and the mutagenicity of the exhaust. Further investigations have to elucidate the causal relationship.

Peptide Conjugated Phosphorodiamidate Morpholino Oligomers Increase Survival of Mice Challenged with Ames Bacillus anthracis

PubMed Central

Geller, Bruce L.; Mellbye, Brett; Lane, Douglas; Iversen, Patrick L.; Bavari, Sina

2012-01-01

Targeting bacterial essential genes using antisense phosphorodiamidate morpholino oligomers (PMOs) represents an important strategy in the development of novel antibacterial therapeutics. PMOs are neutral DNA analogues that inhibit gene expression in a sequence-specific manner. In this study, several cationic, membrane-penetrating peptides were conjugated to PMOs (PPMOs) that target 2 bacterial essential genes: acyl carrier protein (acpP) and gyrase A (gyrA). These were tested for their ability to inhibit growth of Bacillus anthracis, a gram-positive spore-forming bacterium and causative agent of anthrax. PPMOs targeted upstream of both target gene start codons and conjugated with the bacterium-permeating peptide (RFF)3R were found to be most effective in inhibiting bacterial growth in vitro. Both of the gene-targeted PPMOs protected macrophages from B. anthracis induced cell death. Subsequent, in vivo testing of the PPMOs resulted in increased survival of mice challenged with the virulent Ames strain of B. anthracis. Together, these studies suggest that PPMOs targeting essential genes have the potential of being used as antisense antibiotics to treat B. anthracis infections. PMID:22978365

[The hygienic evaluation of the mutagenic potential of industrial wastes].

PubMed

Zhurkov, V S; Rusakov, N V; Tonkopiĭ, N I; Sycheva, L P; Akhal'tseva, L V; Neiaskina, E V; Pirtakhiia, N V; Malysheva, A G; Rastiannikov, E G

1998-01-01

A combination of two approaches to assessing the carcinogenic and mutagenic potentials of industrial waste is proposed. One approach includes determination of the carcinogenic and mutagenic properties of individual chemicals of waste, the other involves biological indication of the cumulative mutagenic activity of waste samples. The mutagenic potential of some waste samples of aircraft industry was determined.

Mutagenicity and genotoxicity of drinking water in Guelma region, Algeria.

PubMed

Abda, Ahlem; Benouareth, Djamel E; Tabet, Mouna; Liman, Recep; Konuk, Muhsin; Khallef, Messaouda; Taher, Ali

2015-02-01

In this study, a battery of genotoxicity assays for monitoring drinking water was performed to assess the quality of the water resulting from the treatment plants. Five different types of samples were collected: raw water (P1), treated after pre-chlorination (P2), treated after decantation (P3), treated post-chlorination (P4), and consumers' taps (P5-P12). This study aims to evaluate the formation/occurrence of mutagenic and/or genotoxic compounds in surface drinking waters treated with chlorine disinfectant, during four seasonal experiments: summer, autumn, winter, and spring between 2012 and 2013 by bacterial reverse mutation assay in both Salmonella typhimurium TA98 and TA100 strains with or without metabolic activation system (S9 mix) and Allium cepa root meristematic cells, respectively. All of water samples, except at P1, P2, and P5 in summer; P1 in autumn; and P1 and P3-P12 in spring without S9 mix, and at P1 and P2 in summer and P6 and P8-P12 in spring with S9 mix, were found to be mutagenic in S. typhimurium TA98. However, only P11 and P12 in winter were found to be mutagenic for TA100 without S9 mix. The tested preparations in Allium anaphase-telophase test revealed a significant decrease in mitotic index (MI) and a simultaneous increase in chromosome aberrations (CAs) compared to the control. The bridge, stickiness, vagrant chromosomes, and disturbed chromosome aberrations were observed in anaphase-telophase cells. Physicochemical analysis, trihalomethanes (THMs), romoform (CHBr3), chloroform (CHCl3), bromodichloromethane (CHBrCl2), and dibromochloromethane (CHBr2Cl) levels in water samples were also determined. The results show also that this short-term battery tests are applicable in the routine monitoring of drinking water quality before and after distribution.

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

PubMed

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.

Selenazolinium Salts as "Small Molecule Catalysts" with High Potency against ESKAPE Bacterial Pathogens.

PubMed

Witek, Karolina; Nasim, Muhammad Jawad; Bischoff, Markus; Gaupp, Rosmarie; Arsenyan, Pavel; Vasiljeva, Jelena; Marć, Małgorzata Anna; Olejarz, Agnieszka; Latacz, Gniewomir; Kieć-Kononowicz, Katarzyna; Handzlik, Jadwiga; Jacob, Claus

2017-12-08

In view of the pressing need to identify new antibacterial agents able to combat multidrug-resistant bacteria, we investigated a series of fused selenazolinium derivatives ( 1 - 8 ) regarding their in vitro antimicrobial activities against 25 ESKAPE-pathogen strains. Ebselen was used as reference compound. Most of the selenocompounds demonstrated an excellent in vitro activity against all S. aureus strains, with activities comparable to or even exceeding the one of ebselen. In contrast to ebselen, some selenazolinium derivatives ( 1 , 3 , and 7 ) even displayed significant actions against all Gram-negative pathogens tested. The 3-bromo-2-(1-hydroxy-1-methylethyl)[1,2]selenazolo[2,3- a ]pyridinium chloride ( 1 ) was particularly active (minimum inhibitory concentrations, MICs: 0.31-1.24 µg/mL for MRSA, and 0.31-2.48 µg/mL for Gram-negative bacteria) and devoid of any significant mutagenicity in the Ames assay. Our preliminary mechanistic studies in cell culture indicated that their mode of action is likely to be associated with an alteration of intracellular levels of glutathione and cysteine thiols of different proteins in the bacterial cells, hence supporting the idea that such compounds interact with the intracellular thiolstat. This alteration of pivotal cysteine residues is most likely the result of a direct or catalytic oxidative modification of such residues by the highly reactive selenium species (RSeS) employed.

Genotoxic potentials of lifestyles assessed by urinary mutagenicity.

PubMed

Mure, K; Morimoto, K

1994-09-01

The relationships between lifestyles and urinary mutagenicity were investigated by using blue rayon extraction from 33 healthy male workers' urine. Subjects were classified into three groups, as "good", "moderate", and "poor" according to their responses on a questionnaire regarding eight health practices (cigarette smoking, alcohol consumption, eating breakfast, hours of sleep, hours of work, physical exercise, caring about nutritional balance, mental stress). The better lifestyle groups exhibited the lower mutagenicity. Subjects in a "good" group showed significantly lower urinary mutagenicity than those both in a "moderate" (p < 0.05) and a "poor" (p < 0.05) groups at fraction number 1 to 3 that were given after ingesting fried beef. These tendencies also found at fraction number 8 to 9 that were given after smoking, although not significant. The lifestyles were significantly associated with the urinary mutagenicity, and the results suggested that not only particular lifestyle factor but also some combinations with smoking significantly enhanced with the urinary mutagenicity.

Probiotic administration effect on fecal mutagenicity and microflora in the goat's gut.

PubMed

Apás, Ana Lidia; Dupraz, Javier; Ross, Romina; González, Silvia Nelina; Arena, Mario Eduardo

2010-11-01

The application of potentially beneficial microorganisms to increase host defense is a new trend to increase health benefits. In this paper the first specific host probiotics for goats from a mixture isolated from healthy animals (Lactobacillus reuteri DDL 19, Lactobacillus alimentarius DDL 48, Enterococcus faecium DDE 39 and Bifidobacterium bifidum DDBA) was assayed. The effect of probiotic oral administration on goats' weight, gut microbiota, as well as on the production of mutagen compounds and their indicator (putrescine), were evaluated. The probiotic supplement was able to modify microflora balance by reducing Enterobacteria like Salmonella/Shigella (1.09 and 1.21 log CFU/g feces, respectively) and increasing lactic acid bacteria and Bifidobacteria (1.67 and 2.34 log CFU/g feces, respectively). The probiotics administration was correlated with a ten time diminution of fecal putrescine (cancer and bacterial disease marker) and a decrease of 60% mutagen fecal concentration, indicating the protective effect of the treatment. Additionally, a significant increase in ruminant weight was observed after probiotic administration. These results are encouraging towards the use of probiotic mixtures as functional food for goats. Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Mutagen Synergy: Hypermutability Generated by Specific Pairs of Base Analogs

PubMed Central

Ang, Jocelyn; Song, Lisa Yun; D'Souza, Sara; Hong, Irene L.; Luhar, Rohan; Yung, Madeline

2016-01-01

ABSTRACT We tested pairwise combinations of classical base analog mutagens in Escherichia coli to study possible mutagen synergies. We examined the cytidine analogs zebularine (ZEB) and 5-azacytidine (5AZ), the adenine analog 2-aminopurine (2AP), and the uridine/thymidine analog 5-bromodeoxyuridine (5BrdU). We detected a striking synergy with the 2AP plus ZEB combination, resulting in hypermutability, a 35-fold increase in mutation frequency (to 53,000 × 10−8) in the rpoB gene over that with either mutagen alone. A weak synergy was also detected with 2AP plus 5AZ and with 5BrdU plus ZEB. The pairing of 2AP and 5BrdU resulted in suppression, lowering the mutation frequency of 5BrdU alone by 6.5-fold. Sequencing the mutations from the 2AP plus ZEB combination showed the predominance of two new hot spots for A·T→G·C transitions that are not well represented in either single mutagen spectrum, and one of which is not found even in the spectrum of a mismatch repair-deficient strain. The strong synergy between 2AP and ZEB could be explained by changes in the dinucleoside triphosphate (dNTP) pools. IMPORTANCE Although mutagens have been widely studied, the mutagenic effects of combinations of mutagens have not been fully researched. Here, we show that certain pairwise combinations of base analog mutagens display synergy or suppression. In particular, the combination of 2-aminopurine and zebularine, analogs of adenine and cytidine, respectively, shows a 35-fold increased mutation frequency compared with that of either mutagen alone. Understanding the mechanism of synergy can lead to increased understanding of mutagenic processes. As combinations of base analogs are used in certain chemotherapy regimens, including those involving ZEB and 5AZ, these results indicate that testing the mutagenicity of all drug combinations is prudent. PMID:27457718

Mutagenicity of urine from individuals exposed to LPG combustion products.

PubMed

Yin, X J; Liu, J Z; Kong, X H; Chu, J H; Wang, H; Xiao, Z X

1998-09-01

The mutagenicity of urine from individuals exposed to the combustion products of liquefied petroleum gas (LPG) was detected with Salmonella typhimurium TA98 and its newly developed derivatives YG1021 (nitroreductase overproducing) and YG1024 (O-acetyltransferase overproducing). The detection showed significantly increased mutagenicity for the two YG strains and increased positive rates for all three strains in the presence of both rat liver S9 and beta-glucuronidase. Further analysis demonstrated that urine samples taken from smoking and non-smoking exposed individuals exhibited significantly higher mutagenic potency (revertants/10 microliters urine concentrate) than their corresponding controls. These results indicate that the increased urine mutagenicity is caused by the exposure to LPG combustion products or smoking. The mutagenic potency of urine samples of all exposed individuals tested with YG1024 was found to be about 7 times higher than with TA98. The difference in mutagenic potency was smaller for the same samples when comparison was made between YG1021 and TA98. This suggests that the mutagenic compounds present in the urine samples contain mainly aromatic compounds as glucuronide conjugates. Our results demonstrate that YG1024 is more sensitive than TA98 in detecting the mutagenicity of these samples. In addition, no significant difference in the mutagenic potency between the 'pure' exposed (non-smokers') and the 'pure' smokers' (unexposed) samples was found in all three tester strains. This might mean that the exposure extent of mutagens/carcinogens in LPG combustion products for exposed individuals roughly corresponds to the smoking level of smokers who smoke 20-40 cigarettes per day. Furthermore, the results also suggest that synergism might exist in the mutagenic effects of exposure to LPG combustion products and cigarette smoking.

Building Climate Resilience at NASA Ames Research Center

NASA Astrophysics Data System (ADS)

Iraci, L. T.; Mueller, C.; Podolske, J. R.; Milesi, C.

2016-12-01

NASA Ames Research Center, located at the southern end of the San Francisco Bay (SFB) estuary, has identified three primary vulnerabilities to changes in climate. The Ames Climate Adaptation Science Investigator (CASI) workgroup has studied each of these challenges to operations and the potential exposure of infrastructure and employees to an increased frequency of hazards. Sea level rise inundation scenarios for the SFB Area generally refer to projected scenarios in mean sea level rather than changes in extreme tides that could occur during future storm conditions. In the summer of 2014, high resolution 3-D mapping of the low-lying portion of Ames was performed. Those data are integrated with improved sea level inundation scenarios to identify the buildings, basements and drainage systems potentially affected. We will also identify the impacts of sea level and storm surge effects on transportation to and from the Center. This information will help Center management develop future master plans. Climate change will also lead to changes in temperature, storm frequency and intensity. These changes have potential impacts on localized floods and ecosystems, as well as on electricity and water availability. Over the coming decades, these changes will be imposed on top of ongoing land use and land cover changes, especially those deriving from continued urbanization and increase in impervious surface areas. These coupled changes have the potential to create a series of cascading impacts on ecosystems, including changes in primary productivity and disturbance of hydrological properties and increased flood risk. The majority of the electricity used at Ames is supplied by hydroelectric dams, which will be influenced by reductions in precipitation or changes in the timing or phase of precipitation which reduces snow pack. Coupled with increased demand for summertime air conditioning and other cooling needs, NASA Ames is at risk for electricity shortfalls. To assess the

Is Tobacco Smoke a Germ-Cell Mutagen?

EPA Science Inventory

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 IBM PC at NASA Ames

NASA Technical Reports Server (NTRS)

Peredo, James P.

1988-01-01

Like many large companies, Ames relies very much on its computing power to get work done. And, like many other large companies, finding the IBM PC a reliable tool, Ames uses it for many of the same types of functions as other companies. Presentation and clarification needs demand much of graphics packages. Programming and text editing needs require simpler, more-powerful packages. The storage space needed by NASA's scientists and users for the monumental amounts of data that Ames needs to keep demand the best database packages that are large and easy to use. Availability to the Micom Switching Network combines the powers of the IBM PC with the capabilities of other computers and mainframes and allows users to communicate electronically. These four primary capabilities of the PC are vital to the needs of NASA's users and help to continue and support the vast amounts of work done by the NASA employees.

Evaluation of photo-mutagenicity and photo-cytotoxicity of food coloring agents.

PubMed

Arimoto-Kobayashi, Sakae; Machida, Masaki; Okamoto, Keinosuke; Yamaguchi, Akie

2005-05-01

Pigments extracted from natural products are widely used for food coloration in Japan. An investigation concerning the photo-mutagenicity and photo-carcinogenicity of frequently used colorants in Japan was performed. Colorants examined were from Laccifer lacca (lac-color), Coccus cacti (cochineal-color), Carthamus tinctorius (carthamus yellow), Gardenia augusta (gardenia yellow and gardenia blue), Monascus anka and Monascus purpureus (monascus red), the skin of Vitis vinifera and Vitis labrusca (grape-skin color), Tamarindus indica (tamarind brown) and Beta vulgaris (beet red). No significant increase in bacterial mutation was found when Salmonella typhimurium TA98, TA100 and TA102 were simultaneously treated with colorants and subjected to UVA irradiation for 30 min. When colorant solutions were subjected to UVA irradiation for 4 h, irradiated solutions containing lac-color became slightly mutagenic toward S.typhimurium TA98 without metabolic activation. A decrease in cell survival resulted when WTK-1 cells were subjected to UVA irradiation for 60 min in the presence of purpurin at 1 mg/ml. Delayed cytotoxicity was also observed following 24 h incubation in fresh medium of samples that were subjected to UVA irradiation for 60 min in the presence of colorant (carthamus yellow, grape-skin color, gardenia blue, cochineal-color, monascus red or purpurin).

TOPICAL REVIEW: MUTAGENICITY AND CARCINOGENICITY OF AIR

EPA Science Inventory

Although both outdoor and indoor airs provide exposure to mutagens and carcinogens, this review shows that the level of hazard is highly variable. Outdoor air was first shown to be carcinogenic in 1942 and mutagenic in 1975; and studies examining the genotoxicity of indoor air so...

Atmosphere of Freedom: Sixty Years at the NASA Ames Research Center

NASA Technical Reports Server (NTRS)

Bugos, Glenn E.; Launius, Roger (Technical Monitor)

2000-01-01

Throughout Ames History, four themes prevail: a commitment to hiring the best people; cutting-edge research tools; project management that gets things done faster, better and cheaper; and outstanding research efforts that serve the scientific professions and the nation. More than any other NASA Center, Ames remains shaped by its origins in the NACA (National Advisory Committee for Aeronautics). Not that its missions remain the same. Sure, Ames still houses the world's greatest collection of wind tunnels and simulation facilities, its aerodynamicists remain among the best in the world, and pilots and engineers still come for advice on how to build better aircraft. But that is increasingly part of Ames' past. Ames people have embraced two other missions for its future. First, intelligent systems and information science will help NASA use new tools in supercomputing, networking, telepresence and robotics. Second, astrobiology will explore lore the prospects for life on Earth and beyond. Both new missions leverage Ames long-standing expertise in computation and in the life sciences, as well as its relations with the computing and biotechnology firms working in the Silicon Valley community that has sprung up around the Center. Rather than the NACA missions, it is the NACA culture that still permeates Ames. The Ames way of research management privileges the scientists and engineers working in the laboratories. They work in an atmosphere of freedom, laced with the expectation of integrity and responsibility. Ames researchers are free to define their research goals and define how they contribute to the national good. They are expected to keep their fingers on the pulse of their disciplines, to be ambitious yet frugal in organizing their efforts, and to always test their theories in the laboratory or in the field. Ames' leadership ranks, traditionally, are cultivated within this scientific community. Rather than manage and supervise these researchers, Ames leadership merely

Mutagenicity of an aged gasworks soil during bioslurry treatment

PubMed Central

Lemieux, Christine L; Lynes, Krista D; White, Paul A; Lundstedt, Staffan; Öberg, Lars; Lambert, Iain B

2009-01-01

This study investigated changes in the mutagenic activity of organic fractions from soil contaminated with polycyclic aromatic hydrocarbons (PAHs) during pilot-scale bioslurry remediation. Slurry samples were previously analyzed for changes in PAH and polycyclic aromatic compound content, and this study examined the correspondence between the chemical and toxicological metrics. Nonpolar neutral and semipolar aromatic fractions of samples obtained on days 0, 3, 7, 24, and 29 of treatment were assayed for mutagenicity using the Salmonella mutation assay. Most samples elicited a significant positive response on Salmonella strains TA98, YG1041, and YG1042 with and without S9 metabolic activation; however, TA100 failed to detect mutagenicity in any sample. Changes in the mutagenic activity of the fractions across treatment time and metabolic activation conditions suggests a pattern of formation and transformation of mutagenic compounds that may include a wide range of PAH derivatives such as aromatic amines, oxygenated PAHs, and S-heterocyclic compounds. The prior chemical analyses documented the formation of oxygenated PAHs during the treatment (e.g., 4-oxapyrene-5-one), and the mutagenicity analyses showed high corresponding activity in the semipolar fraction with and without metabolic activation. However, it could not be verified that these specific compounds were the underlying cause of the observed changes in mutagenic activity. The results highlight the need for concurrent chemical and toxicological profiling of contaminated sites undergoing remediation to ensure elimination of priority contaminants as well as a reduction in toxicological hazard. Moreover, the results imply that remediation efficacy and utility be evaluated using both chemical and toxicological metrics. Environ. Mol. Mutagen. 2009. © 2009 Wiley-Liss, Inc. PMID:19274766

Mutagenicity in emissions from coal- and oil-fired boilers.

PubMed Central

Alfheim, I; Bergström, J G; Jenssen, D; Møller, M

1983-01-01

The mutagenicity of emission samples from three oil-fired and four coal-fired boilers have been compared by using the Salmonella/microsome assay. Very little or no mutagenic activity was observed in samples from five of these boilers. The sample from one oil-fired boiler showed mutagenic activity of about 500 revertants/MJ, and the sample from a coal-fired fluidized bed combustor had an activity of 58,000 revertants/MJ measured with strain TA 98 in the absence of metabolic activation. All samples contained substances that were cytotoxic to the test bacteria, thus making it difficult to obtain linear dose-response curves. Mutagenic activity at low levels may remain undetected due to this toxicity of the samples. Samples with mutagenic activity below the detection limit in the Salmonella test have also been tested for forward mutations at the HGPRT locus in V79 hamster cells. Weak mutagenic effects were detected in two of the samples, whereas the sample from one oil-fired boiler remained negative. In this test, as well as in the Salmonella test, a strong cytotoxic effect could be observed with all samples. PMID:6825617

Effect aquadest-extracted Gloriosa superba seed as mutagen on morphology of Artemisia annua

NASA Astrophysics Data System (ADS)

Rahmawati, S. I.; Susilowati, A.; Yunus, A.; Widyastuti, Y.

2018-03-01

Gloriosa superba is a plant that contains colchicine in all parts of organs, especially in the seeds. Its extract is as a mutagen to produce plants with polyploid cells. Artemisia annua is a plant that produces active ingredients artemisinin as malarial drugs, hemorrhoids therapy, aromatherapy, antiviral, anticancer, and anti-bacterial. The aims of this research was to determine the effect aquadest-extracted Gloriosa superba seed as a mutagen to Artemisia annua morphology. Extraction of Gloriosa superba seeds obtained from Sukoharjo using maceration method with aquadest solvent (1: 1). The extracts were diluted (0, 25, 50, 75 and 100%) for Artemisia annua sprinkling with different times (0, 30, 60 and 90 minutes). Observations of morphology Artemisia annua included height, stem circumference, number of branches, number of leaves, leaf width and leaf length. The treatments did not affect plant morphology observation included height, stem circumference, number of branches, number of leaves, leaf width, and leaf length. The EB treatment (100%, 30 minutes) was higher (120 cm) than other. In all treatments stem circumference about 2.5 cm, number of branches ranged between 40-50, leaves width ranged 9-16c m, and leaf length ranged 8-15 cm.

Potential of plant genetic systems for monitoring and screening mutagens

PubMed Central

Nilan, R. A.

1978-01-01

Plants have too long been ignored as useful screening and monitoring systems of environmental mutagens. However, there are about a dozen reliable, some even unique, plant genetic systems that can increase the scope and effectiveness of chemical and physical mutagen screening and monitoring procedures. Some of these should be included in the Tier II tests. Moreover, plants are the only systems now in use as monitors of genetic effects caused by polluted atmosphere and water and by pesticides. There are several major advantages of the plant test systems which relate to their reproductive nature, easy culture and growth habits that should be considered in mutagen screening and monitoring. In addition to these advantages, the major plant test systems exhibit numerous genetic and chromosome changes for determining the effects of mutagens. Some of these have not yet been detected in other nonmammalian and mammalian test systems, but probably occur in the human organism. Plants have played major roles in various aspects of mutagenesis research, primarily in mutagen screening (detection and verification of mutagenic activity), mutagen monitoring, and determining mutagen effects and mechanisms of mutagen action. They have played lesser roles in quantification of mutagenic activity and understanding the nature of induced mutations. Mutagen monitoring with plants, especially in situ on land or in water, will help determine potential genetic hazards of air and water pollutants and protect the genetic purity of crop plants and the purity of the food supply. The Tradescantia stamen-hair system is used in a mobile laboratory for determining the genetic effects of industrial and automobile pollution in a number of sites in the U.S.A. The fern is employed for monitoring genetic effects of water pollution in the Eastern states. The maize pollen system and certain weeds have monitored genetic effects of pesticides. Several other systems that have considerable value and should be

Dietary Mutagen Exposure and Risk of Pancreatic Cancer

PubMed Central

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

2007-01-01

To investigate the association between dietary exposure to food mutagens and risk of pancreatic cancer, we conducted a hospital-based case-control study at the University of Texas M. D. Anderson Cancer Center during June 2002 to May 2006. Atotal of 626 cases and 530 noncancer controls were frequency matched for race, sex and age (±5 years). Dietary exposure information was collected via personal interview using a meat preparation questionnaire. A significantly greater portion of the cases 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 (Ptrend= 0.024). Ahigher 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. Apossible synergistic effect of dietary mutagen exposure and smoking was observed among individuals with the highest level of exposure (top 10%) to PhIP and BaP, Pinteraction= 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. PMID:17416754

Dietary mutagen exposure and risk of pancreatic cancer.

PubMed

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.

Welcome to Ames Research Center (1987 forum on Federal technology transfer)

NASA Technical Reports Server (NTRS)

Ballhaus, William F., Jr.

1988-01-01

NASA Ames Research Center has a long and distinguished history of technology development and transfer. Recently, in a welcoming speech to the Forum on Federal Technology Transfer, Director Ballhouse of Ames described significant technologies which have been transferred from Ames to the private sector and identifies future opportunities.

Effects of diet composition on mutagenic activity in urine.

PubMed

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.

Organic emissions from coal pyrolysis: mutagenic effects.

PubMed Central

Braun, A G; Wornat, M J; Mitra, A; Sarofim, A F

1987-01-01

Four different types of coal have been pyrolyzed in a laminar flow, drop tube furnace in order to establish a relationship between polycyclic aromatic compound (PAC) evolution and mutagenicity. Temperatures of 900K to 1700K and particle residence times up to 0.3 sec were chosen to best simulate conditions of rapid rate pyrolysis in pulverized (44-53 microns) coal combustion. The specific mutagenic activity (i.e., the activity per unit sample weight) of extracts from particulates and volatiles captured on XAD-2 resin varied with coal type according to the order: subbituminous greater than high volatile bituminous greater than lignite greater than anthracite. Total mutagenic activity (the activity per gram of coal pyrolyzed), however, varied with coal type according to the order: high volatile bituminous much greater than subbituminous = lignite much greater than anthracite, due primarily to high organic yield during high volatile bituminous coal pyrolysis. Specific mutagenic activity peaked in a temperature range of 1300K to 1500K and generally appeared at higher temperatures and longer residence times than peak PAC production. PMID:3311724

Ames Research Center Publications-1976

NASA Technical Reports Server (NTRS)

Sherwood, B.

1978-01-01

Bibliography of the publications of Ames Research Center authors and contractors, which appeared in formal NASA publications, journal articles, books, chapters of books, patents, and contractor reports. Covers 1976.

Quantifying Climate Change Hydrologic Risk at NASA Ames Research Center

NASA Astrophysics Data System (ADS)

Mills, W. B.; Bromirski, P. D.; Coats, R. N.; Costa-Cabral, M.; Fong, J.; Loewenstein, M.; Milesi, C.; Miller, N.; Murphy, N.; Roy, S.

2013-12-01

In response to 2009 Executive Order 13514 mandating U.S. federal agencies to evaluate infrastructure vulnerabilities due to climate variability and change we provide an analysis of future climate flood risk at NASA Ames Research Center (Ames) along South S.F. Bay. This includes likelihood analysis of large-scale water vapor transport, statistical analysis of intense precipitation, high winds, sea level rise, storm surge, estuary dynamics, saturated overland flooding, and likely impacts to wetlands and habitat loss near Ames. We use the IPCC CMIP5 data from three Atmosphere-Ocean General Circulation Models with Radiative Concentration Pathways of 8.5 Wm-2 and 4.5 Wm-2 and provide an analysis of climate variability and change associated with flooding and impacts at Ames. Intense storms impacting Ames are due to two large-scale processes, sub-tropical atmospheric rivers (AR) and north Pacific Aleutian low-pressure (AL) storm systems, both of which are analyzed here in terms of the Integrated Water Vapor (IWV) exceeding a critical threshold within a search domain and the wind vector transporting the IWV from southerly to westerly to northwesterly for ARs and northwesterly to northerly for ALs and within the Ames impact area during 1970-1999, 2040-2069, and 2070-2099. We also include a statistical model of extreme precipitation at Ames based on large-scale climatic predictors, and characterize changes using CMIP5 projections. Requirements for levee height to protect Ames are projected to increase and continually accelerate throughout this century as sea level rises. We use empirical statistical and analytical methods to determine the likelihood, in each year from present through 2099, of water level surpassing different threshold values in SF Bay near NASA Ames. We study the sensitivity of the water level corresponding to a 1-in-10 and 1-in-100 likelihood of exceedance to changes in the statistical distribution of storm surge height and ENSO height, in addition to

Silver nanoparticles: correlating nanoparticle size and cellular uptake with genotoxicity

PubMed Central

Butler, Kimberly S.; Peeler, David J.; Casey, Brendan J.; Dair, Benita J.; Elespuru, Rosalie K.

2015-01-01

The focus of this research was to develop a better understanding of the pertinent physico-chemical properties of silver nanoparticles (AgNPs) that affect genotoxicity, specifically how cellular uptake influences a genotoxic cell response. The genotoxicity of AgNPs was assessed for three potential mechanisms: mutagenicity, clastogenicity and DNA strand-break-based DNA damage. Mutagenicity (reverse mutation assay) was assessed in five bacterial strains of Salmonella typhimurium and Echerichia coli, including TA102 that is sensitive to oxidative DNA damage. AgNPs of all sizes tested (10, 20, 50 and 100nm), along with silver nitrate (AgNO3), were negative for mutagenicity in bacteria. No AgNPs could be identified within the bacteria cells using transmission electron microscopy (TEM), indicating these bacteria lack the ability to actively uptake AgNPs 10nm or larger. Clastogenicity (flow cytometry-based micronucleus assay) and intermediate DNA damage (DNA strand breaks as measured in the Comet assay) were assessed in two mammalian white blood cell lines: Jurkat Clone E6-1 and THP-1. It was observed that micronucleus and Comet assay end points were inversely correlated with AgNP size, with smaller NPs inducing a more genotoxic response. TEM results indicated that AgNPs were confined within intracellular vesicles of mammalian cells and did not penetrate the nucleus. The genotoxicity test results and the effect of AgNO3 controls suggest that silver ions may be the primary, and perhaps only, cause of genotoxicity. Furthermore, since AgNO3 was not mutagenic in the gram-negative bacterial Ames strains tested, the lack of bacterial uptake of the AgNPs may not be the major reason for the lack of genotoxicity observed. PMID:25964273

Biochemical mutagens affect the preservation of fungi and biodiversity estimations.

PubMed

Paterson, R Russell M; Lima, Nelson

2013-01-01

Many fungi have significant industrial applications or biosafety concerns and maintaining the original characteristics is essential. The preserved fungi have to represent the situation in nature for posterity, biodiversity estimations, and taxonomic research. However, spontaneous fungal mutations and secondary metabolites affecting producing fungi are well known. There is increasing interest in the preservation of microbes in Biological Resource Centers (BRC) to ensure that the organisms remain viable and stable genetically. It would be anathema if they contacted mutagens routinely. However, for the purpose of this discussion, there are three potential sources of biochemical mutagens when obtaining individual fungi from the environment: (a) mixtures of microorganisms are plated routinely onto growth media containing mutagenic antibiotics to control overgrowth by contaminants, (b) the microbial mixtures may contain microorganisms capable of producing mutagenic secondary metabolites, and (c) target fungi for isolation may produce "self" mutagens in pure culture. The probability that these compounds could interact with fungi undermines confidence in the preservation process and the potential effects of these biochemical mutagens are considered for the first time on strains held in BRC in this review.

Food mutagens: The role of cooked food in genetic changes

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

NONE

1995-07-01

Of all the toxic substances producing during cooking, the most important are likely to be the heterocyclic amines. For 17 years, LLNL researchers have been identifying these food mutagens, measuring their abundance in cooked foods typical of the Western diet, working to understand how they can trigger malignant tumors in laboratory animals that have been exposed to high mutagen doses, and estimating the importance of human exposures. Our success is largely a function of the interdisciplinary approach we have taken to quantify food mutagens and to study their biological effects. LLNL investigators were the first to identify five of themore » most important mutagens in heated food, including PhIP and DiMeIQx. We have shown that fried beef may be the most important single source of heterocyclic amines in the human diet and the PhIP accounts for most of the combined mass of mutagens in fried beef cooked well-done. Most nonmeat foods contain low or undetectable levels of these types of compounds, but some cooked protein-containing foods, such as those high in wheat gluten, have significant levels of unknown aromatic amine mutagens. Cooking time and temperature significantly affect the amounts of mutagens generated. For example, reducing the frying temperature of ground beef from 250 to 200{degrees}C lowers the mutagenic activity by six- to sevenfold. Microwave pretreatment of meat and discarding the liquid that is formed also greatly reduces the formation of heterocyclic amines. Our related work on dose and risk assessment will be described in a forthcoming article.« less

Ames Lab 101: osgBullet

ScienceCinema

McCorkle, Doug

2017-12-27

Ames Laboratory scientist Doug McCorkle explains osgBullet, a 3-D virtual simulation software, and how it helps engineers design complex products and systems in a realistic, real-time virtual environment.

Mutagenicity of airborne particulates in the rubber industry.

PubMed

Barański, B; Indulski, J; Janik-Spiechowicz, E; Palus, J

1989-12-01

The aim of this work was to evaluate the mutagenic activity of airborne particulate matter in the rubber industry. Air was sucked through Whatman glass-fibre filters with Staplex pumps and adsorbed substances and fume particles were extracted with acetone or toluene for 2 h in a ultrasonic cleaner. After separation of the insoluble solid phase by filtration, solvent was evaporated at a temperature of 70 degrees C in an argon atmosphere. The residue was stored at -20 degrees C. Mutagenicity was determined by the Salmonella plate incorporation assay with the tester strain TA98 and activity is related either to the weight of aerosol (rev mg-1) or to the volume of atmospheric sample (rev m-3). The fumes emitted from the tyre tread line, calender feeding, and tyre vulcanizing processes, showed the highest mutagenic activity (55-211 rev mg-1, + S9). At these and at other workplaces (extruder mill, carbon black station, mixer loading), mutagenic activity related to the volume of air was in the range of 22-158 rev m-3, + S9. The results indicate the need to reduce and monitor mutagenic contamination in order to increase the safety of work in the rubber industry.

Predictive Models for Carcinogenicity and Mutagenicity ...

EPA Pesticide Factsheets

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

Changes in mutagenicity of protein pyrolyzates by reaction with nitrite.

PubMed

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.

Genotoxicity in native fish associated with agricultural runoff events

USGS Publications Warehouse

Whitehead, Andrew; Kuivila, Kathryn; Orlando, James L.; Kotelevtsev, S.; Anderson, Susan L.

2004-01-01

The primary objective of the present study was to test whether agricultural chemical runoff was associated with in-stream genotoxicity in native fish. Using Sacramento sucker (Catostomus occidentalis), we combined field-caging experiments in an agriculturally dominated watershed with controlled laboratory exposures to field-collected water samples, and we coupled genotoxicity biomarker measurements in fish with bacterial mutagenicity analysis of water samples. We selected DNA strand breakage as a genotoxicity biomarker and Ames Salmonella mutagenicity tests as a second, supporting indicator of genotoxicity. Data from experiments conducted during rainfall runoff events following winter application of pesticides in 2000 and 2001 indicated that DNA strand breaks were significantly elevated in fish exposed to San Joaquin River (CA, USA) water (38.8, 28.4, and 53.6% DNA strand breakage in year 2000 field, year 2000 lab, and year 2001 field exposures, respectively) compared with a nearby reference site (15.4, 8.7, and 12.6% DNA strand breakage in year 2000 field, year 2000 lab, and year 2001 field exposures, respectively). Time-course measurements in field experiments supported a linkage between induction of DNA strand breakage and the timing of agricultural runoff. San Joaquin River water also caused significant reversion mutation in two Ames Salmonella tester strains. Salmonella mutagenicity corroborated in-stream effects, further strengthening a causal relationship between runoff events and genotoxicity. Potentially responsible agents are discussed in the context of timing of runoff events in the field, concordance between laboratory and field exposures, pesticide application patterns in the drainage, and analytical chemistry data.

Ames Laboratory site environmental report, calendar year 1988

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

Mathison, L.K.

1989-05-01

The summarized data and conclusions from the Ames Laboratory environmental monitoring program are presented in this Annual Site Environmental Report. Ames Laboratory is located on the campus of Iowa State University (ISU) and occupies several buildings owned by the Department of Energy. A study is being conducted to identify environmental sampling methods which can characterize and separate the impact of Ames Laboratory's campus activities and that of ISU. This will enable the Laboratory to determine what possible impact it's operations may be having to the environment, if any. Two Pollution Abatement projects were begun in 1988. They were: removal ofmore » thorium contaminated soil resulting from a historical release of thorium at the Laboratory, to the Ames, Iowa Water Pollution Control (sewage) Plant and demolition of a small Blockhouse'' constructed of concrete block which had been used for low level radioactive waste handling. The contaminated soil has been removed and transported to Hanford, WA for disposal. A final site radiological survey for thorium is pending. In addition, contaminated debris was transported to Hanford, WA for disposal and a final site survey is pending. 7 refs., 4 figs., 1 tab.« less

Prediction of genotoxic potential of cosmetic ingredients by an in silico battery system consisting of a combination of an expert rule-based system and a statistics-based system.

PubMed

Aiba née Kaneko, Maki; Hirota, Morihiko; Kouzuki, Hirokazu; Mori, Masaaki

2015-02-01

Genotoxicity is the most commonly used endpoint to predict the carcinogenicity of chemicals. The International Conference on Harmonization (ICH) M7 Guideline on Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk offers guidance on (quantitative) structure-activity relationship ((Q)SAR) methodologies that predict the outcome of bacterial mutagenicity assay for actual and potential impurities. We examined the effectiveness of the (Q)SAR approach with the combination of DEREK NEXUS as an expert rule-based system and ADMEWorks as a statistics-based system for the prediction of not only mutagenic potential in the Ames test, but also genotoxic potential in mutagenicity and clastogenicity tests, using a data set of 342 chemicals extracted from the literature. The prediction of mutagenic potential or genotoxic potential by DEREK NEXUS or ADMEWorks showed high values of sensitivity and concordance, while prediction by the combination of DEREK NEXUS and ADMEWorks (battery system) showed the highest values of sensitivity and concordance among the three methods, but the lowest value of specificity. The number of false negatives was reduced with the battery system. We also separately predicted the mutagenic potential and genotoxic potential of 41 cosmetic ingredients listed in the International Nomenclature of Cosmetic Ingredients (INCI) among the 342 chemicals. Although specificity was low with the battery system, sensitivity and concordance were high. These results suggest that the battery system consisting of DEREK NEXUS and ADMEWorks is useful for prediction of genotoxic potential of chemicals, including cosmetic ingredients.

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

EPA Pesticide Factsheets

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.

PubMed

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.

Mutagenicity of 1-nitropyrene metabolites from lung S9.

PubMed

King, L C; Kohan, M J; Ball, L M; Lewtas, J

1984-04-01

The mutagenicity of 1-nitropyrene metabolites from rabbit lung S9 incubates was evaluated using the Salmonella typhimurium plate incorporation assay with strain TA98, with and without Aroclor-induced rat liver S9. The following metabolites were isolated, identified and quantitated by HPLC: 1-nitropyrene -4,5- or -9,10-dihydrodiol (K-DHD), N-acetyl-1-aminopyrene ( NAAP ), 1-aminopyrene (1-AMP), 10-hydroxy-1-nitropyrene, 4-, 5-, 6-, 8- or 9-monohydroxy-1-nitropyrene (phenols) and 3-hydroxy-1-nitropyrene. The predominant metabolites formed by lung S9 incubates were K-DHD, 3-OH-1-nitropyrene and phenols. All of the metabolites were mutagenic in the absence of the exogenous rat liver S9 metabolic activation system, and several, including two unidentified metabolites were more potent than the parent 1-nitropyrene. The mutagenicity of 3 of the metabolites ( NAAP , 10-OH-1-nitropyrene and phenols) were enhanced by S9 while most of the other metabolites were less mutagenic in the presence of S9. These results indicate that lung tissue is capable of both oxidative and reductive metabolism which produced mutagenic metabolites, several of which were more potent than the parent compound, 1-NP.

Ames research center publications, 1975

NASA Technical Reports Server (NTRS)

Sherwood, B. R. (Compiler)

1977-01-01

This bibliography cites 851 documents by Ames Research Center personnel and contractors which appeared in formal NASA publications, journals, books, patents, and contractor reports in 1975, or not included in previous annual bibliographies. An author index is provided.

Evaluation of the systemic toxicity and mutagenicity of OLIGOPIN®, procyanidolic oligomers (OPC) extracted from French Maritime Pine Bark extract.

PubMed

Segal, L; Penman, M G; Piriou, Y

2018-01-01

The potential systemic toxicity of Oligopin®, a French Maritime Pine Bark extract (FMPBE) rich in procyanidolic oligomers, was evaluated in an acute oral limit test and a 90-day repeated dose oral toxicity study with Sprague Dawley rats. The potential mutagenicity was assessed in a bacterial reverse mutation assay and in vitro mammalian chromosome aberration assay with human lymphocytes. The results indicate that Oligopin® was nongenotoxic in both bacterial and human cell assays, was not acutely toxic via oral administration at up to 2000 mg/kg and was well tolerated following 90 days of oral administration to SD rats, with a no observed adverse effect level of 1000 mg/kg/day. The lack of significant adverse systemic effects in the 90 day study is concordant with findings from several human clinical trials. The acute toxicity and mutagenicity data are consistent with data reported by AFSSA in a summary of FMPBE safety, in which a NOAEL of 100 mg/kg/day was established. In contrast, the NOAEL derived from the 90-day study with Oligopin® was 1000 mg/kg/day, suggesting that it is less systemically toxic than other FMPBE previously evaluated in subchronic studies, and comparable to proanthocyanidins extracted from grape seeds, which are widely used as nutritional supplement ingredients.

Mutagens and carcinogens - Occurrence and role during chemical and biological evolution

NASA Technical Reports Server (NTRS)

Giner-Sorolla, A.; Oro, J.

1981-01-01

The roles of mutagenic and carcinogenic substances in early biologic evolution is examined, along with terrestrial and extraterrestrial sources of mutagens and carcinogens. UV solar radiation is noted to have served to stimulate prebiotic life while also causing harmful effects in plants and animals. Aromatic compounds have been found in meteorites, and comprise leukemogens, polycyclic hydrocarbons, and nitrasamine precursors. Other mutagenic sources are volcanoes, and the beginning of evolution with mutagenic substances is complicated by the appearance of malignancies due to the presence of carcinogens. The atmosphere of the Precambrian period contained both mutagens and early carcinogens and, combined with volcanic activity discharges, formed an atmospheric chemical background analogous to the background ionizing radiation. Carcinogenesis is concluded to be intrinsic to nature, having initiated evolution and, eventually, cancer cells.

Center Overview and UAV Highlights at NASA Ames Research Center

NASA Technical Reports Server (NTRS)

Feng, Deborah; Yan, Jerry Chi Yiu

2017-01-01

The PowerPoint presentation gives an overview of NASA Ames Research Center and its core competencies, as well as some of the highlights of Unmanned Aerial Vehicle (UAV) and Unmanned Aircraft Systems (UAS) accomplishments and innovations by researchers at Ames.

Brown Adipose Tissue Function Is Enhanced in Long-Lived, Male Ames Dwarf Mice

PubMed Central

McFadden, Samuel; Fang, Yimin; Huber, Joshua A.; Zhang, Chi; Sun, Liou Y.; Bartke, Andrzej

2016-01-01

Ames dwarf mice (Prop1df/df) are long-lived due to a loss of function mutation, resulting in deficiency of GH, TSH, and prolactin. Along with a marked extension of longevity, Ames dwarf mice have improved energy metabolism as measured by an increase in their oxygen consumption and heat production, as well as a decrease in their respiratory quotient. Along with alterations in energy metabolism, Ames dwarf mice have a lower core body temperature. Moreover, Ames dwarf mice have functionally altered epididymal white adipose tissue (WAT) that improves, rather than impairs, their insulin sensitivity due to a shift from pro- to anti-inflammatory cytokine secretion. Given the unique phenotype of Ames dwarf epididymal WAT, their improved energy metabolism, and lower core body temperature, we hypothesized that Ames dwarf brown adipose tissue (BAT) may function differently from that of their normal littermates. Here we use histology and RT-PCR to demonstrate that Ames dwarf mice have enhanced BAT function. We also use interscapular BAT removal to demonstrate that BAT is necessary for Ames dwarf energy metabolism and thermogenesis, whereas it is less important for their normal littermates. Furthermore, we show that Ames dwarf mice are able to compensate for loss of interscapular BAT by using their WAT depots as an energy source. These findings demonstrate enhanced BAT function in animals with GH and thyroid hormone deficiencies, chronic reduction of body temperature, and remarkably extended longevity. PMID:27740871

Transcriptional Characterization of Salmonella TAl00 in Growth and Stationary Phase: Mutagenesis of MX in Both Types of Cells

EPA Science Inventory

The Salmonella (Ames) mutagenicity assay can be performed using cells that are in different growth phases. Thus, the plate-incorporation assay involves plating stationary-phase cells with the mutagen, after which the cells undergo a brief lag phase and, consequently, are exposed ...

NASA Ames Research Center Air Traffic Management Research Overview

NASA Technical Reports Server (NTRS)

Lozito, Sandy

2017-01-01

This is a presentation to the Owl Feather Society, a group of people who are retired from NASA Ames Research Center. I am providing a summary of the ATM research here at NASA Ames to this group as part of a lunch time talk series. The presentation will be at Michael's Restaurant in Mountain View, CA on July 18.

Role of Mutagenicity in Asbestos Fiber-Induced Carcinogenicity and Other Diseases

PubMed Central

Huang, Sarah X. L.; Jaurand, Marie-Claude; Kamp, David W.; Whysner, John; Hei, Tom K.

2011-01-01

The cellular and molecular mechanisms of how asbestos fibers induce cancers and other diseases are not well understood. Both serpentine and amphibole asbestos fibers have been shown to induce oxidative stress, inflammatory responses, cellular toxicity and tissue injuries, genetic changes, and epigenetic alterations in target cells in vitro and tissues in vivo. Most of these mechanisms are believe to be shared by both fiber-induced cancers and noncancerous diseases. This article summarizes the findings from existing literature with a focus on genetic changes, specifically, mutagenicity of asbestos fibers. Thus far, experimental evidence suggesting the involvement of mutagenesis in asbestos carcinogenicity is more convincing than asbestos-induced fibrotic diseases. The potential contributions of mutagenicity to asbestos-induced diseases, with an emphasis on carcinogenicity, are reviewed from five aspects: (1) whether there is a mutagenic mode of action (MOA) in fiber-induced carcinogenesis; (2) mutagenicity/carcinogenicity at low dose; (3) biological activities that contribute to mutagenicity and impact of target tissue/cell type; (4) health endpoints with or without mutagenicity as a key event; and finally, (5) determinant factors of toxicity in mutagenicity. At the end of this review, a consensus statement of what is known, what is believed to be factual but requires confirmation, and existing data gaps, as well as future research needs and directions, is provided. PMID:21534089

Mutagenicity of diesel engine exhaust is eliminated in the gas phase by an oxidation catalyst but only slightly reduced in the particle phase.

PubMed

Westphal, Götz A; Krahl, Jürgen; Munack, Axel; Ruschel, Yvonne; Schröder, Olaf; Hallier, Ernst; Brüning, Thomas; Bünger, Jürgen

2012-06-05

Concerns about adverse health effects of diesel engine emissions prompted strong efforts to minimize this hazard, including exhaust treatment by diesel oxidation catalysts (DOC). The effectiveness of such measures is usually assessed by the analysis of the legally regulated exhaust components. In recent years additional analytical and toxicological tests were included in the test panel with the aim to fill possible analytical gaps, for example, mutagenic potency of polycyclic aromatic hydrocarbons (PAH) and their nitrated derivatives (nPAH). This investigation focuses on the effect of a DOC on health hazards from combustion of four different fuels: rapeseed methyl ester (RME), common mineral diesel fuel (DF), SHELL V-Power Diesel (V-Power), and ARAL Ultimate Diesel containing 5% RME (B5ULT). We applied the European Stationary Cycle (ESC) to a 6.4 L turbo-charged heavy load engine fulfilling the EURO III standard. The engine was operated with and without DOC. Besides regulated emissions we measured particle size and number distributions, determined the soluble and solid fractions of the particles and characterized the bacterial mutagenicity in the gas phase and the particles of the exhaust. The effectiveness of the DOC differed strongly in regard to the different exhaust constituents: Total hydrocarbons were reduced up to 90% and carbon monoxide up to 98%, whereas nitrogen oxides (NO(X)) remained almost unaffected. Total particle mass (TPM) was reduced by 50% with DOC in common petrol diesel fuel and by 30% in the other fuels. This effect was mainly due to a reduction of the soluble organic particle fraction. The DOC caused an increase of the water-soluble fraction in the exhaust of RME, V-Power, and B5ULT, as well as a pronounced increase of nitrate in all exhausts. A high proportion of ultrafine particles (10-30 nm) in RME exhaust could be ascribed to vaporizable particles. Mutagenicity of the exhaust was low compared to previous investigations. The DOC reduced

Mutagenic Activity of Indigofera truxillensis and I. suffruticosa Aerial Parts

PubMed Central

Calvo, Tamara Regina; Cardoso, Cássia Regina Primila; da Silva Moura, Adriana Candido; dos Santos, Lourdes Campaner; Colus, Ilce Mara Syllos; Vilegas, Wagner; Varanda, Eliana Aparecida

2011-01-01

Indigofera truxillensis and I. suffruticosa, are used as a source of indigo dye and to treat several diseases. The mutagenic activity of the methanolic extracts from aerial parts, glycerolipid, flavonoid and alkaloid fractions of the extract were evaluated by means of Salmonella/microsome assays using TA100, TA98, TA102 and TA97a strains. The methanolic extract of I. truxillensis showed mutagenic activity in the TA98 strain without S9 while glycerolipid fraction was devoid of activity. The flavonoid and alkaloid fractions of both plants showed mutagenicity. Chemical analysis of flavonoid fractions of I. truxillensis and I. suffruticosa resulted in the identification of kaempferol, quercetin and their derivatives. The alkaloid fraction of both the species contained indigo and indirubin and indigo was found mainly responsible for the mutagenic activity. PMID:19696193

NASA Administrator Visits Ames Research Center (Reporter Pkg - May 2013)

NASA Image and Video Library

2013-05-24

NASA Administrator Charles Bolden and Congressman Mike Honda (D-San Jose, CA) were special guests at Ames Research Center recently. During their visit, they visited the SpaceShop, where they were shown demonstrations of Ames' contributions to the PhoneSat nano-satellite mission and 3D printing activity

Identification of potential fish carcinogens in sediment from Hamilton Harbour, Ontario, Canada

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

Balch, G.C.; Metcalfe, C.D.; Huestis, S.Y.

1995-01-01

A carcinogenicity- and mutagenicity-directed fractionation approach was used to identify the carcinogenic compounds in contaminated sediments that are putatively responsible for the high prevalence of tumors in bottom-dwelling fish from Hamilton Harbour, Ontario. Mutagenic activity was detected with Ames tester strains (TA98, TA100) in relatively nonpolar fractions of sediment extract containing PAHs and nitrogen-containing aromatic compounds (NCACs). These fractions were also carcinogenic in an in vivo carcinogenicity bioassay with rainbow trout (Oncorhynchus mykiss). When a more polar extract fraction was tested for mutagenicity and carcinogenicity, weak mutagenic activity was detected with an O-acetyltransferase-enriched Ames tester strain (YG1024), and weak carcinogenicmore » activity was detected in the rainbow trout assay. These data indicate that PAHs in contaminated Hamilton Harbour sediments are potent fish carcinogens, but it is also evident that other organic compounds in the sediment, such as NCACs and nitroarenes, may contribute to carcinogenicity.« less

NASA Ames ATM Research

NASA Technical Reports Server (NTRS)

Denery, Dallas G.

2000-01-01

The NASA Ames research Center, in cooperation with the FAA and the industry, has a series of major research efforts underway that are aimed at : 1) improving the flow of traffic in the national airspace system; and 2) helping to define the future air traffic management system. The purpose of this presentation will be to provide a brief summary of some of these activities.

Ozonation of mutagenic and carcinogenic polyaromatic amines and polyaromatic hydrocarbons in water

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

Burleson, G.R.; Caulfield, M.J.; Pollard, M.

1979-06-01

The Salmonella-microsome assay for mutagenesis was used to determine the effect of ozone on the mutagenesis of selected carcinogens and mutagens in water. Short periods of ozonation were shown to completely inactivate the mutagenicity of several polyaromatic amine mutagens including acriflavine, proflavine, and beta-naphthylamine. Selected polyaromatic hydrocarbons were also sensitive to ozonation. Kinetic studies revealed that the mutagenicity of benzo(a)pyrene, 3-methylcholanthrene, and 7,12-dimethylbenz(a)anthracene was destroyed after short periods of ozonation. To correlate loss of mutagenicity with loss of carcinogenicity, two polyaromatic hydrocarbons were treated with ozone, extracted from water with hexane, and tested for carcinogenicity in mice. When 7,12-dimethyl-benz(a)anthracene andmore » 3-methyl-cholanthrene were treated with ozone, there was a substantial reduction in carcinogenicity compared to control groups treated with oxygen alone. However, a small number of tumors developed in the group of animals receiving a hexane extract of ozonated 7,12-dimethylbenz(a)anthracene. This activity may be due to breakdown products of 7,12-dimethylbenz(a)anthracene that are not mutagenic.« less

Evaluation of genetic toxicity of 6-diazo-5-oxo-l-norleucine (DON).

PubMed

Kulkarni, Rohan M; Dakoulas, Emily W; Miller, Ken E; Terse, Pramod S

2017-09-01

DON (6-diazo-5-oxo-l-norleucine), a glutamine antagonist, was demonstrated to exhibit analgesic, antibacterial, antiviral and anticancer properties. The study was performed to characterize its in vitro and in vivo genetic toxicity potential. DON was tested in the bacterial reverse mutation assay (Ames test) using Salmonella typhimurium tester strains (TA98, TA100, TA1535 and TA1537) and Escherichia coli tester strain (WP2 uvrA) with and without S9 and also with reductive S9. In addition, DON was tested for the chromosome aberrations in Chinese hamster ovary (CHO) cells with or without S9 to evaluate the clastogenic potential. Furthermore, DON was also evaluated for its in vivo clastogenic activity by detecting micronuclei in polychromatic erythrocyte (PCE) cells in bone marrow collected from the male mice dosed intravenously with 500, 100, 10, 1 and 0.1 mg/kg at 24 and 48-h post-dose. The Ames mutagenicity assay showed no positive mutagenic responses. However, the in vitro chromosome aberration assay demonstrated dose dependent statistically positive increase in structural aberrations at 4 and 20-h exposure without S9 and also at 4-h exposure with S9. The in vivo micronucleus assay also revealed a statistically positive response for micronucleus formation at 500, 100 and 10 mg/kg at 24 and 48-h post-dose. Thus, DON appears to be negative in the Ames test but positive in the in vitro chromosome aberration assay and in the in vivo micronucleus assay. In conclusion, the results indicate DON is a genotoxic compound with a plausible epigenetic mechanism.

Ames Engineering Directorate

NASA Technical Reports Server (NTRS)

Phillips, Veronica J.

2017-01-01

The Ames Engineering Directorate is the principal engineering organization supporting aerospace systems and spaceflight projects at NASA's Ames Research Center in California's Silicon Valley. The Directorate supports all phases of engineering and project management for flight and mission projects-from R&D to Close-out-by leveraging the capabilities of multiple divisions and facilities.The Mission Design Center (MDC) has full end-to-end mission design capability with sophisticated analysis and simulation tools in a collaborative concurrent design environment. Services include concept maturity level (CML) maturation, spacecraft design and trades, scientific instruments selection, feasibility assessments, and proposal support and partnerships. The Engineering Systems Division provides robust project management support as well as systems engineering, mechanical and electrical analysis and design, technical authority and project integration support to a variety of programs and projects across NASA centers. The Applied Manufacturing Division turns abstract ideas into tangible hardware for aeronautics, spaceflight and science applications, specializing in fabrication methods and management of complex fabrication projects. The Engineering Evaluation Lab (EEL) provides full satellite or payload environmental testing services including vibration, temperature, humidity, immersion, pressure/altitude, vacuum, high G centrifuge, shock impact testing and the Flight Processing Center (FPC), which includes cleanrooms, bonded stores and flight preparation resources. The Multi-Mission Operations Center (MMOC) is composed of the facilities, networks, IT equipment, software and support services needed by flight projects to effectively and efficiently perform all mission functions, including planning, scheduling, command, telemetry processing and science analysis.

AME - Asteroseismology Made Easy. Estimating stellar properties by using scaled models

NASA Astrophysics Data System (ADS)

Lundkvist, Mia; Kjeldsen, Hans; Silva Aguirre, Victor

2014-06-01

Context. Stellar properties and, in particular stellar radii of exoplanet host stars, are essential for measuring the properties of exoplanets, therefore it is becoming increasingly important to be able to supply reliable stellar radii fast. Grid-modelling is an obvious choice for this, but that only offers a low degree of transparency to non-specialists. Aims: Here we present a new, easy, fast, and transparent method of obtaining stellar properties for stars exhibiting solar-like oscillations. The method, called Asteroseismology Made Easy (AME), can determine stellar masses, mean densities, radii, and surface gravities, as well as estimate ages. We present AME as a visual and powerful tool that could be useful, in particular, in light of the large number of exoplanets being found. Methods: AME consists of a set of figures from which the stellar parameters can be deduced. These figures are made from a grid of stellar evolutionary models that cover masses ranging from 0.7 M⊙ to 1.6 M⊙ in steps of 0.1 M⊙ and metallicities in the interval -0.3 dex ≤ [Fe/H] ≤ +0.3 dex in increments of 0.1 dex. The stellar evolutionary models are computed using the Modules for Experiments in Stellar Astrophysics (MESA) code with simple input physics. Results: We have compared the results from AME with results for three groups of stars: stars with radii determined from interferometry (and measured parallaxes), stars with radii determined from measurements of their parallaxes (and calculated angular diameters), and stars with results based on modelling their individual oscillation frequencies. We find that a comparison of the radii from interferometry to those from AME yields a weighted mean of the fractional differences of just 2%. This is also the level of deviation that we find when we compare the parallax-based radii to the radii determined from AME. Conclusions: The comparison between independently determined stellar parameters and those found using AME show that our method

Making Stuff Outreach at the Ames Laboratory and Iowa State University

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

Ament, Katherine; Karsjen, Steven; Leshem-Ackerman, Adah

The U. S. Department of Energy's Ames Laboratory in Ames, Iowa was a coalition partner for outreach activities connected with NOVA's Making Stuff television series on PBS. Volunteers affiliated with the Ames Laboratory and Iowa State University, with backgrounds in materials science, took part in activities including a science-themed Family Night at a local mall, Science Cafes at the Science Center of Iowa, teacher workshops, demonstrations at science nights in elementary and middle schools, and various other events. We describe a selection of the activities and present a summary of their outcomes and extent of their impact on Ames, Desmore » Moines and the surrounding communities in Iowa. In Part 2, results of a volunteer attitude survey are presented, which shed some light on the volunteer experience and show how the volunteers participation in outreach activities has affected their views of materials education.« less

Mutagenic substances in pyrolysate obtained by burning polyvinylchloride-product at 1000 degrees C.

PubMed

Yonezawa, Y; Saigusa, S; Takahagi, M; Nishioka, H

1999-06-25

In order to detect possible mutagenic substances in pyrolysate obtained by burning polyvinyl chloride product (PVC-P) at approximately 1000 degrees C, mutagenicity of rough extracts obtained by extraction with various solvents for the products was investigated by means of reversion mutation assay using Salmonella typhimurium TA98 and TA100 with or without microsomal metabolic activation (S9 mix). Strong mutagenicity in TA98 without S9 mix was observed in acetone-extract of PVC-P. The extract was fractionated into acidic, neutral and basic by liquid-liquid distribution and the mutagenicity in TA98 without S9 mix was found in the neutral fraction. Identification of mutagenic substances in the neutral fraction from acetone extract, which showed the strongest mutagenicity, was attempted by means of thin layer chromatography and capillary gas chromatography. The results suggest that mutagenic substances from pyrolysate of PVC-P are benzanthrone and an isomer of benzo(c)cinnoline. The results also suggest that burning wastes containing plastic products is not always safe even if at 1000 degrees C and further research on the problem is necessary. Copyright 1999 Elsevier Science B.V.

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

PubMed

Barrington, P J; Baker, R S; Truswell, A S; Bonin, A M; Ryan, A J; Paulin, A P

1990-03-01

Mutagen production was examined in lamb and beef in relation to certain common household cooking methods. Mutagenicity was assessed, after extraction of the basic fraction of cooked meat samples, using Salmonella typhimurium strain TA1538 with added rat-liver S-9 homogenate. Little or no mutagenicity was found in barbecued lamb chops, in microwave-cooked lamb chops, sirloin steak, leg of lamb, or rolled beef loaf, in roasted leg of lamb or rolled beef loaf, in stewed blade steak or in boiled chuck steak. However, the basic fraction from well-done, edible fried or grilled meat contained mutagenic activity equivalent to approximately 30,000 TA1538 revertants/100 g cooked meat. It was found tht the mutagenic activity of grilled lamb chops, sirloin and rump steaks was directly related to the average surface temperatures attained during cooking. Use of butter as a frying medium was particularly associated with higher mutagenicity in meat samples. Fried meats (rump and fillet steaks) generally yielded higher mutagenic activity than did grilled meats (rump steak, lamb chops) at comparable temperatures of the cooking medium. Using similar cooking procedures, lamb did not differ markedly from beef in mutagenic activity.

Pointing to potential reference areas to assess soil mutagenicity.

PubMed

Meyer, D D; Da Silva, F M R; Souza, J W M; Pohren, R S; Rocha, J A V; Vargas, V M F

2015-04-01

Several have been performed to evaluate the mutagenicity of soil samples in urban and industrial areas. The use of uncontaminated reference areas has been an obstacle to the study of environmental mutagenesis. The study aimed to indicate a methodology to define reference areas in studies of environmental contamination based on "Ambient Background Concentration" of metallic elements associated with the Salmonella/microsome assay. We looked at three potential reference areas, two of them close by the industrial sources of contamination (São Jerônimo reference, near the coal-fired power plant, and Triunfo reference, near the wood preservative plant), but not directly influenced by them and an area located inside a protected area (Itapuã reference). We also carried out chemical analyses of some metals to plot the metal profile of these potential reference areas and define basal levels of these metals in the soils. After examining the mutagenicity of the inorganic extracts using strains TA98, TA97a, and TA100, in the presence and absence of S9 mix, we indicated the São Jerônimo reference and the Itapuã reference as two sites that could be used in future studies of mutagenicity of soils in southern Brazil. The association between a mutagenicity bioassay and the "Ambient Background Concentration" seems to be a useful method to indicate the reference areas in studies of contamination by environmental mutagens, where these results were corroborated by canonical correspondence analysis.

Ames Research Center cryogenics program

NASA Technical Reports Server (NTRS)

Kittel, Peter

1987-01-01

Viewgraphs describe the Ames Research Center's cryogenics program. Diagrams are given of a fluid management system, a centrifugal pump, a flow meter, a liquid helium test facility, an extra-vehicular activity coupler concept, a dewar support with passive orbital disconnect, a pulse tube refrigerator, a dilution refrigerator, and an adiabatic demagnetization cooler.

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

PubMed Central

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

1986-01-01

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

Monitoring hospital wastewaters for their probable genotoxicity and mutagenicity.

PubMed

Sharma, Pratibha; Mathur, N; Singh, A; Sogani, M; Bhatnagar, P; Atri, R; Pareek, S

2015-01-01

Cancer is a leading cause of death worldwide. Excluding the genetic factors, environmental factors, mainly the pollutants, have been implicated in the causation of the majority of cancers. Wastewater originated from health-care sectors such as hospitals may carry vast amounts of carcinogenic and genotoxic chemicals to surface waters or any other source of drinking water, if discharged untreated. Humans get exposed to such contaminants through a variety of ways including drinking water. The aim of the present study was, thus, to monitor the genotoxic and mutagenic potential of wastewaters from three big hospitals located in Jaipur (Rajasthan), India. One of them was operating an effluent treatment plant (ETP) for treatment of its wastewater and therefore both the untreated and treated effluents from this hospital were studied for their genotoxicity. Two short-term bacterial bioassays namely the Salmonella fluctuation assay and the SOS chromotest were used for the purpose. Results of fluctuation assay revealed the highly genotoxic nature of all untreated effluent samples with mutagenicity ratios (MR) up to 23.13 ± 0.18 and 42.25 ± 0.35 as measured with Salmonella typhimurium strains TA98 and TA100, respectively. As determined with the chromotest, all untreated effluents produced significant induction factors (IF) ranging from 3.29 ± 1.11 to 13.35 ± 3.58 at higher concentrations. In contrast, treated effluent samples were found to be slightly genotoxic in fluctuation test only with an MR = 3.75 ± 0.35 for TA100 at 10 % concentration. Overall, the results indicated that proper treatment of hospital wastewaters may render the effluents safe for disposal contrary to the untreated ones, possessing high genotoxic potential.

Anti-Helicobacter pylori activities of selected N-substituted cinnamamide derivatives evaluated on reference and clinical bacterial strains.

PubMed

Klesiewicz, Karolina; Karczewska, Elżbieta; Nowak, Paweł; Skiba-Kurek, Iwona; Sito, Edward; Pańczyk, Katarzyna; Koczurkiewicz, Paulina; Żelaszczyk, Dorota; Pękala, Elżbieta; Waszkielewicz, Anna M; Budak, Alicja; Marona, Henryk; Gunia-Krzyżak, Agnieszka

2018-05-01

In this study, thirty-five N-substituted derivatives of cinnamic acid amide (cinnamamide) were evaluated for anti-Helicobacter pylori activity using an agar disc-diffusion method. Qualitative screening was performed on a reference H. pylori strain (ATCC 43504), resulting in the identification of the three most active compounds, 8 (R,S-(2E)-3-(4-chlorophenyl)-N-(2-hydroxypropyl)prop-2-enamide, minimal inhibitory concentration, MIC = 7.5 µg/mL), 23 ((2E)-3-(4-chlorophenyl)-N-(2-hydroxycyclohexyl)prop-2-enamide, MIC = 10 µg/mL), and 28 ((2E)-3-(4-chlorophenyl)-N-(4-oxocyclohexyl)prop-2-enamide, MIC = 10 µg/mL). These compounds were further tested on twelve well-characterized clinical strains, yielding MIC values that ranged from 10 to 1000 µg/mL. Preliminary safety assessments of the compounds were made using the MTT viability test for cytotoxicity and Ames test for mutagenicity, which showed them to be generally safe, although compounds 8 and 28 showed mutagenic activity at some of the tested concentrations. The results of this study showed the anti-H. pylori potential of cinnamamide derivatives.

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

PubMed Central

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

2016-01-01

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

Mutagenicity of comfrey (Symphytum Officinale) in rat liver

PubMed Central

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

2005-01-01

Comfrey is a rat liver toxin and carcinogen that has been used as a vegetable and herbal remedy by humans. In order to evaluate the mechanisms underlying its carcinogenicity, we examined the mutagenicity of comfrey in the transgenic Big Blue rat model. Our results indicate that comfrey is mutagenic in rat liver and the types of mutations induced by comfrey suggest that its tumorigenicity results from the genotoxicity of pyrrolizidine alkaloids in the plant. PMID:15726100

Evaluation of the cytotoxicity, genotoxicity, mutagenicity, and antimutagenicity of propolis from Tucuman, Argentina.

PubMed

Nieva Moreno, María I; Zampini, Iris C; Ordóñez, Roxana M; Jaime, Gloria S; Vattuone, Marta A; Isla, María I

2005-11-16

This study evaluates the toxic, genotoxic/mutagenic, and antimutagenic effects of propolis extract from Amaicha del Valle, Tucumán, Argentina. The cytotoxicity assays carried out with the lethality test of Artemia salina revealed that the LD50 was around 100 microg/mL. Propolis extracts showed no toxicity to Salmonella typhimurium TA98 and TA100 strains and Allium cepa at concentrations that have antibiotic and antioxidant activities. Otherwise, for the testing doses, neither genotoxicity nor mutagenicity was found in any sample. The propolis extracts were able to inhibit the mutagenesis of isoquinoline (IQ) and 4-nitro o-phenylenediamine (NPD) with ID50 values of 40 and 20 microg/plate, respectively. From this result, the studied propolis may be inferred to contain some chemical compounds capable of inhibiting the mutagenicity of direct-acting and indirect-acting mutagens. A compound isolated from Amaicha del Valle propolis, 2',4'-dihydroxychalcone, showed cytotoxic activity (LC50 values of 0.5 microg/mL) but was not genotoxic or mutagenic. Furthermore, this compound was able to inhibit the mutagenicity of IQ (ID50 values of 1 microg/plate) but was unable to inhibit the mutagenicity of NPD. Our results suggest a potential anticarcinogenic activity of Amaicha del Valle propolis and the chalcone isolated from it.

Mutagenic effect of freezing on mitochondrial DNA of Saccharomyces cerevisiae.

PubMed

Stoycheva, T; Venkov, P; Tsvetkov, Ts

2007-06-01

Although suggested in some studies, the mutagenic effect of freezing has not been proved by induction and isolation of mutants. Using a well-defined genetic model, we supply in this communication evidence for the mutagenic effect of freezing on mitochondrial DNA (mtDNA) of the yeast Saccharomyces cerevisiae. The cooling for 2 h at +4 degrees C, followed by freezing for 1 h at -10 degrees C and 16 h at -20 degrees C resulted in induction of respiratory mutations. The immediate freezing in liquid nitrogen was without mutagenic effect. The study of the stepwise procedure showed that the induction of respiratory mutants takes place during the freezing at -10 and -20 degrees C of cells pre-cooled at +4 degrees C. The genetic crosses of freeze-induced mutants evidenced their mitochondrial rho- origin. The freeze-induced rho- mutants are most likely free of simultaneous nuclear mutations. The extracellular presence of cryoprotectants did not prevent the mutagenic effect of freezing while accumulation of cryoprotectors inside cells completely escaped mtDNA from cryodamage. Although the results obtained favor the notion that the mutagenic effect of freezing on yeast mtDNA is due to formation and growth of intracellular ice crystals, other reasons, such as impairment of mtDNA replication or elevated levels of ROS production are discussed as possible explanations of the mutagenic effect of freezing. It is concluded that: (i) freezing can be used as a method for isolation of mitochondrial mutants in S. cerevisiae and (ii) given the substantial development in cryopreservation of cells and tissues, special precautions should be made to avoid mtDNA damage during the cryopreservation procedures.

Genotoxicity of quinocetone, cyadox and olaquindox in vitro and in vivo.

PubMed

Ihsan, Awais; Wang, Xu; Zhang, Wei; Tu, Honggang; Wang, Yulian; Huang, Lingli; Iqbal, Zahid; Cheng, Guyue; Pan, Yuanhu; Liu, Zhenli; Tan, Ziqiang; Zhang, Yuanyuan; Yuan, Zonghui

2013-09-01

Quinocetone (QCT) and Cyadox (CYA) are important derivative of heterocyclic N-oxide quinoxaline (QdNO), used actively as antimicrobial feed additives in China. Here, we tested and compared the genotoxic potential of QCT and CYA with olaquindox (OLA) in Ames test, HGPRT gene mutation (HGM) test in V79 cells, unscheduled DNA synthesis (UDS) assay in human peripheral lymphocytes, chromosome aberration (CA) test, and micronucleus (MN) test in mice bone marrow. OLA was found genotoxic in all 5 assays. In Ames test, QCT produced His(+) mutants at 6.9 μg/plate in Salmonella typhimurium TA 97, at 18.2 μg/plate in TA 100, TA 1535, TA 1537, and at 50 μg/plate in TA 98. CYA produced His(+) mutants at 18.2 μg/plate in TA 97, TA 1535, and at 50 μg/plate in TA 98, TA 100 and TA 1537. QCT was found positive in HGM and UDS assay at concentrations ≥10 μg/ml while negative results were reported in CA test and MN test. Collectively, we found that OLA was more genotoxic than QCT and CYA. Genotoxicity of QCT was found at higher concentration levels in Ames test, HGM and UDS assays while CYA showed weak mutagenic potential to bacterial cells in Ames test. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ames Lab 101: Single Crystal Growth

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

Schlagel, Deborah

2013-09-27

Ames Laboratory scientist Deborah Schlagel talks about the Lab's research in growing single crystals of various metals and alloys. The single crystal samples are vital to researchers' understanding of the characteristics of a materials and what gives these materials their particular properties.

Ames Lab 101: Single Crystal Growth

ScienceCinema

Schlagel, Deborah

2018-01-16

Ames Laboratory scientist Deborah Schlagel talks about the Lab's research in growing single crystals of various metals and alloys. The single crystal samples are vital to researchers' understanding of the characteristics of a materials and what gives these materials their particular properties.

Personal thoughts on the future of the Environmental Mutagen Society.

PubMed

Brusick, D

1994-01-01

The Environmental Mutagen Society (EMS) was one of the first professional scientific societies organized to respond to an environmental concern. The threat of environmental pollution stimulated the formation of the organization in 1969. The Society's mission was to create a forum for discussion of methods and strategies to deal with mutagenic agents formed and/or released into the environment. During the past 25 years, EMS has provided a forum for innovation and scientific discussions. The Environmental Mutagen Society, and, in particular, its applied role in genetic toxicology, has had a profound positive impact on many disciplines in toxicology and safety assessment (i.e., carcinogenesis and in vitro alternatives.

Review: putative mutagens and carcinogens in foods. VII. Genetic toxicology of the diet

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

Hatch, F.T.; MacGregor, J.T.; Zeiger, E.

Individual reviews of approximately 30 papers presented at the Fourth International Conference on Environmental Mutagens are presented in this report. Topics covered include diet in cancer epidemiology; cooked and processed food as a source of mutagens and carcinogens; natural genotoxins in plants and beverages; mutagens within the gastrointestinal tract; and modulation of mutagenesis and carcinogenesis.

In vitro genotoxicity of chlorinated drinking water processed from humus-rich surface water

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

Liimatainen, A.; Grummt, T.

Chlorination by-products of drinking waters are capable of inducing sister chromatid exchanges (SCE) and chromosome aberrations (CA) in vitro, in addition to their mutagenic activity in the Ames test. Finnish drinking waters, processed from humus-rich surface water using chlorine disinfection, have been found to be highly mutagenic in the Ames' test. The highest activities have been found in the acidic, non-volatile fraction of the water concentrates using tester strain TA100 without metabolic activation by S9mix. The mutagenicities have varied between 500 and 14,000 induced revertants per liter. These figures are one to two magnitudes higher than those reported elsewhere. Themore » authors studied five Finnish drinking water samples for their potency to exert genotoxic effects, SCEs and CAs, in mammalian cells in vitro (human peripheral lymphocytes and Chinese hamster lung fibroblasts).« less

A novel genotoxic aspect of thiabendazole as a photomutagen in bacteria and cultured human cells.

PubMed

Watanabe-Akanuma, Mie; Ohta, Toshihiro; Sasaki, Yu F

2005-09-15

Thiabendazole (TBZ) is a post-harvest fungicide commonly used on imported citrus fruits. We recently found that TBZ showed photomutagenicity with UVA-irradiation in the Ames test using plate incorporation method. In the present study, potential of DNA-damaging activity, mutagenicity, and clastogenicity were investigated by short pulse treatment for 10 min with TBZ (50-400 microg/ml) and UVA-irradiation (320-400 nm, 250 microW/cm2) in bacterial and human cells. UVA-irradiated TBZ caused DNA damage in Escherichia coli and human lymphoblastoid WTK1 cells assayed, respectively, by the umu-test and the single cell gel electrophoresis (comet) assay. In a modified Ames test using Salmonella typhimurium and E. coli, strong induction of -1 frameshift mutations as well as base-substitution mutations were detected. TBZ at 50-100 microg/ml with UVA-irradiation significantly induced micronuclei in WTK1 cells in the in vitro cytochalasin-B micronucleus assay. Pulse treatment for 10 min with TBZ alone did not show any genotoxicity. Although TBZ is a spindle poison that induces aneuploidy, we hypothesize that the photogenotoxicity of TBZ in the present study was produced by a different mechanism, probably by DNA adduct formation. We concluded that UVA-activated TBZ is genotoxic in bacterial and human cells in vitro.

REVIEW OF THE SALMONELLA TYPHIMURIUM MUTAGENICITY OF BENZIDINE, BENZIDINE ANALOGUES, AND BENZIDINE-BASED DYES

EPA Science Inventory

The mutagenicity of benzidine analogues (including benzidine-based dyes) was reviewed with a primary emphasis on evaluating results of the Salmonella/microsome mutagenicity assay. Many of these amines are mutagenic in tester strains TA98 and TA100 but require exogenous mammalian ...

NASA-Ames vertical gun

NASA Technical Reports Server (NTRS)

Schultz, P. H.

1984-01-01

A national facility, the NASA-Ames vertical gun range (AVGR) has an excellent reputation for revealing fundamental aspects of impact cratering that provide important constraints for planetary processes. The current logistics in accessing the AVGR, some of the past and ongoing experimental programs and their relevance, and the future role of this facility in planetary studies are reviewed. Publications resulting from experiments with the gun (1979 to 1984) are listed as well as the researchers and subjects studied.

Cytotoxic, mutagenicity, and genotoxicity effects of guanylhydrazone derivatives.

PubMed

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

2016-08-01

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

Ames Lab 101: BAM (Boron-Aluminum-Magnesium)

ScienceCinema

Cook, Bruce

2017-12-13

Materials scientist, Bruce Cook, discusses the super hard, low friction, and lubricious alloy know as BAM (Boron-Aluminum-Magnesium). BAM was discovered by Bruce Cook and his team at the Ames Laboratory.

Ames Lab 101: Reinventing the Power Cable

ScienceCinema

Russell, Alan

2018-01-16

Ames Laboratory researchers are working to develop new electrical power cables that are stronger and lighter than the cables currently used in the nation's power grid. Nano Tube animation by Iain Goodyear

Mutagenicity of diesel exhaust particle extracts: influence of fuel composition in two diesel engines

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

Clark, C.R.; Henderson, T.R.; Royer, R.E.

The influence of diesel fuel composition on mutagenicity of exhaust particle associated organic compounds has been investigated using nine fuels varying in aromatic content and distillation properties. The tests were conducted with Oldsmobile Delta-88 and Peugot 504 diesel cars operated according to the EPA Federal Test Procedure. The particulate exhaust from each test was collected on a filter, extracted in dichloromethane and the resulting extract evaluated for mutagenicity in Salmonella strain TA-100. Mutagenicity of extracts of particles collected from the Oldsmobile were highest in the higher aromatic content fuels (> 30%) but similar for intermediate (20%) and low (13%) aromaticmore » content fuels. No influence of aromaticity on mutagenicity was observed in samples collected from the Peugeot under the same conditions. Thus, fuel aromatic content may enhance the production of mutagenic combustion products at higher concentrations, but may be dependent upon engine type. A good correlation was observed between mutagenicity of the particle extracts and the initial boiling point of the fuel (r = 0.89). Gas chromatography/mass spectrometric analysis of the aromatic fraction of the fuels showed that the fuel producing the most mutagenic combustion products was highest in phenanthrene type compounds.« less

NASA Ames Celebrates Curiosity Rover's Landing on Mars (Reporter Package)

NASA Image and Video Library

2012-08-08

Nearly 7,000 people came to NASA Ames Research Center, Moffett Field, Calif., to watch the Mars Science Laboratory rover Curiosity land on Mars. A full day's worth of activities and discussions with local Mars experts informed attendees about the contributions NASA Ames made to the mission. The highlight of the event was the live NASA TV broadcast of MSL's entry, descent and landing on the Martian surface.

Carcinogenicity and Mutagenicity Data: New Initiatives to ...

EPA Pesticide Factsheets

Currents models for prediction of chemical carcinogenicity and mutagenicity rely upon a relatively small number of publicly available data resources, where the data being modeled are highly summarized and aggregated representations of the actual experimental results. A number of new initiatives are underway to improve access to existing public carcinogenicity and mutagenicity data for use in modeling, as well as to encourage new approaches to the use of data in modeling. Rodent bioassay results from the NIEHS National Toxicology Program (NTP) and the Berkeley Carcinogenic Potency Database (CPDB) have provided the largest public data resources for building carcinogenicity prediction models to date. However, relatively few and limited representations of these data have actually informed existing models. Initiatives, such as EPA's DSSTox Database Network, offer elaborated and quality reviewed presentations of the CPDB and expanded data linkages and coverage of chemical space for carcinogenicity and mutagenicity. In particular the latest published DSSTox CPDBAS structure-data file includes a number of species-specific and summary activity fields, including a species-specific normalized score for carcinogenic potency (TD50) and various weighted summary activities. These data are being incorporated into PubChem to provide broad

Exposure related mutagens in urine of rubber workers associated with inhalable particulate and dermal exposure

PubMed Central

Vermeulen, R; Bos, R; Pertijs, J; Kromhout, H

2003-01-01

Aims: To determine the relation of the inhalation and dermal exposure routes and mutagenic activity in the urine of rubber workers (n = 105). Methods: Mutagenic activity of ambient total suspended particulate matter (TSPM), surface contamination wipes, and Sunday and weekday urine samples was assessed with S typhimurium YG1041 in the presence of a metabolic activation system. Each subject was grouped into one of two exposure categories for dermal exposure (high (≥25 revertants/cm2), low (<25 revertants/cm2)) based on the mutagenic activity detected on likely skin contact surfaces and into two airborne mutagenic exposure categories (high (≥210 revertants/m3), low (<210 revertants/m3)). The potential influence of skin aberrations and acetylation status (NAT2) on urinary mutagenicity levels was also evaluated. Results: A non-significant increase of +1605 revertants/g creatinine in urinary mutagenicity during the workweek relative to levels observed on Sunday was observed for the total population. Subsequent multivariate regression analyses, with the subjects' weekday urinary mutagenicity levels as the dependent variable, revealed associations with environmental and mainstream tobacco smoke exposure, with the level of mutagenic contamination on surfaces with which the subjects had likely contact, with the subjects' inhalable particulate exposure level, with observed mild skin aberrations, and when the subjects had a slow acetylation phenotype. Similar associations, although weaker were observed with Sunday urinary mutagenicity levels as well, except for the association with slow acetylation phenotype. Based on measured exposure levels it could be estimated that a high potential for exposure to surface contamination with mutagenic activity increased weekday urinary mutagenicity by about 62% when compared to low exposed workers, while high inhalable particulate exposure levels increased weekday urinary mutagenicity levels by about 21%. Subjects with mild skin

Mutagenicity of streptozotocin and several other nitrosourea compounds in Salmonella typhimurium.

PubMed

Zimmer, D M; Bhuyan, B K

1976-11-01

The following nitrosourea compounds were compared for their ability to induce mutation (to histidine independence) in the histidine-requiring auxotroph Salmonella typhimurium his G46: MNU, streptozotocin (SZ, streptozocin) and its analogs SZA1 and SZA2, and the antitumor drugs BCNU, CCNU and DCNU. At equitoxic doses SZ, SZA1, SZA2 and MNU were almost equally mutagenic causing 150, 42, 140 and 170 mutants/106 survivors at 20% lethal dose (ID20) ALTHOUGH, ON A WIEGHT BASIS, SZ was the most mutagenic of all the compounds tested. At ID20 BCNU, CCNU and DCNU gave about 0.5 mutants/106 survivors. Our results show that these nitrosoureas, in common with many other drugs (such as cyclophosphamide, daunomycin, etc.) used in cancer chemotherapy, are highly mutagenic. The implication of our results in the screening of drugs for their mutagenicity to man is discussed.

Ames Lab 101: Next Generation Power Lines

ScienceCinema

Russell, Alan

2017-12-22

Ames Laboratory scientist Alan Russell discusses the need to develop new power lines that are stronger and more conductive as a way to address the problem of the nation's aging and inadequate power grid.

Cultivating a Grassroots Aerospace Innovation Culture at NASA Ames Research Center

NASA Technical Reports Server (NTRS)

D'Souza, Sarah; Sanchez, Hugo; Lewis, Ryan

2017-01-01

This paper details the adaptation of specific 'knowledge production' methods to implement a first of its kind, grassroots event that provokes a cultural change in how the NASA Ames civil servant community engages in the creation and selection of innovative ideas. Historically, selection of innovative proposals at NASA Ames Research Center is done at the highest levels of management, isolating the views and perspectives of the larger civil servant community. Additionally, NASA innovation programs are typically open to technical organizations and do not engage non-technical organizations to bring forward innovative processes/business practices. Finally, collaboration on innovative ideas and associated solutions tend to be isolated to organizational silos. In this environment, not all Ames employees feel empowered to innovate and opportunities for employee collaboration are limited. In order to address these issues, the 'innovation contest' method was adapted to create the NASA Ames Innovation Fair, a unique, grassroots innovation opportunity for the civil servant community. The Innovation Fair consisted of a physical event with a virtual component. The physical event provided innovators the opportunity to collaborate and pitch their innovations to the NASA Ames community. The civil servant community then voted for the projects that they viewed as innovative and would contribute to NASA's core mission, making this event a truly grassroots effort. The Innovation Fair website provided a location for additional knowledge sharing, discussion, and voting. On March 3rd, 2016, the 'First Annual NASA Ames Innovation Fair' was held with 49 innovators and more than 300 participants collaborating and/or voting for the best innovations. Based on the voting results, seven projects were awarded seed funding for projects ranging from innovative cost models to innovations in aerospace technology. Surveys of both innovators and Fair participants show the Innovation Fair was successful

Mutagenic atmospheres resulting from the photooxidation of aromatic hydrocarbon and NOx mixtures

NASA Astrophysics Data System (ADS)

Riedel, Theran P.; DeMarini, David M.; Zavala, Jose; Warren, Sarah H.; Corse, Eric W.; Offenberg, John H.; Kleindienst, Tadeusz E.; Lewandowski, Michael

2018-04-01

Although many volatile organic compounds (VOCs) are regulated to limit air pollution and the consequent health effects, the photooxidation products generally are not. Thus, we examined the mutagenicity in Salmonella TA100 of photochemical atmospheres generated in a steady-state atmospheric simulation chamber by irradiating mixtures of single aromatic VOCs, NOx, and ammonium sulfate seed aerosol in air. The 10 VOCs examined were benzene; toluene; ethylbenzene; o-, m-, and p-xylene; 1,2,4- and 1,3,5-trimethylbenzene; m-cresol; and naphthalene. Salmonella were exposed at the air-agar interface to the generated atmospheres for 1, 2, 4, 8, or 16 h. Dark-control exposures produced non-mutagenic atmospheres, illustrating that the gas-phase precursor VOCs were not mutagenic at the concentrations tested. Under irradiation, all but m-cresol and naphthalene produced mutagenic atmospheres, with potencies ranging from 2.0 (p-xylene) to 11.4 (ethylbenzene) revertants m3 mgC-1 h-1. The mutagenicity was due exclusively to direct-acting late-generation products of the photooxidation reactions. Gas-phase chemical analysis showed that a number of oxidized organic chemical species enhanced during the irradiated exposure experiments correlated (r ≥ 0.81) with the mutagenic potencies of the atmospheres. Molecular formulas assigned to these species indicated that they likely contained peroxy acid, aldehyde, alcohol, and other functionalities.

Addition Polyimides from Non-Mutagenic Diamines

NASA Technical Reports Server (NTRS)

Delvigs, Peter; Klopotek, David L.; Hardy-Green, DeNise; Meador, Michael A. (Technical Monitor)

2001-01-01

Studies were conducted to find an acceptable non-mutagenic diamine to replace 4,4'-methylenedianiline (MDA), a suspect carcinogen, which is currently being used in PMR-15 polyimide applications. Several diamines containing fluorine and trifluoromethyl substituent groups were synthesized. The diamines were polymerized with the dimethyl ester of 3,3',4,4'-benzophenone tetracarboxylic acid (BTDE), using the monomethyl ester of nadic acid (NE) as an endcap. The effect of diamine structure on rheological properties, glass transition temperature, and thermo-oxidative stability was investigated. Unidirectional laminates were fabricated from selected resins, using carbon fiber as the reinforcement. The results indicate that some of the diamines containing trifluoromethyl groups are non-mutagenic, and have potential to replace MDA in PMR polyimides for long-term applications at temperatures up to 300 C.

Ames-2016 line lists for 13 isotopologues of CO2: Updates, consistency, and remaining issues

NASA Astrophysics Data System (ADS)

Huang (黄新川), Xinchuan; Schwenke, David W.; Freedman, Richard S.; Lee, Timothy J.

2017-12-01

A new 626-based Ames-2 PES refinement and Ames-2016 line lists for 13 CO2 isotopologues are reported. A consistent σRMS = ±0.02 cm-1 is established for hundreds of isotopologue band origins using the Ames-2 PES. Ames-2016 line lists are computed at 296 K, 1000 K and 4000 K using the Ames-2 PES and the same DMS-N2 dipole surface used previously, with J up to 150, E‧ up to 24,000 cm-1 or 18,000 cm-1 and appropriate intensity cutoffs. The lists are compared to the CDSD-296, CDSD-4000 databases, UCL line lists, and a few recent highly accurate CO2 intensity measurements. Both agreements and discrepancies are discussed. Compared to the old Ames CO2 lists, the Ames-2016 line lists have line position deviations reduced by 50% or more, which consequently leads to more reliable intensities. The line shape parameters in the Ames-2016 line lists are predicted using the newly assigned conventional vibrational polyad quantum numbers for rovibrational levels below 12,000 cm-1 so the quality of the line shape parameters is similar to that of CDSD or HITRAN. This study further proves that a semi-empirically refined PES (Ames-1 and Ames-2) coupled with a high quality ab initio DMS (DMS-N2 and UCL) may generate IR predictions with consistent accuracy and is thus helpful in the analysis of laboratory spectra and simulations of various isotopologues. The Ames-2016 lists based on DMS-N2 have reached the ∼1% intensity prediction accuracy level for the recent 626 30013-00001 and 20013-00001 bands, but further quantification and improvements require sub-percent or sub-half-percent accurate experimental intensities. The inter-isotopologue consistency of the intensity prediction accuracies should have reached better than 1-3% for regular bands not affected by resonances. Since the Effective Dipole Models (EDM) in CDSD and HITRAN have 1-20% or even larger uncertainties, we show that the Ames lists can provide better alternative IR data for many hard-to-determine isotopologue bands

Environmental nitration processes enhance the mutagenic potency of aromatic compounds.

PubMed

Bonnefoy, Aurélie; Chiron, Serge; Botta, Alain

2012-05-01

This work is an attempt to establish if aromatic nitration processes are always associated with an increase of genotoxicity. We determined the mutagenic and genotoxic effects of Benzene (B), Nitrobenzene (NB), Phenol (P), 2-Nitrophenol (2-NP), 2,4-Dinitrophenol (2,4-DNP), Pyrene (Py), 1-Nitropyrene (1-NPy), 1,3-Dinitropyrene (1,3-DNPy), 1,6-Dinitropyrene (1,6-DNPy), and 1,8-Dinitropyrene (1,8-DNPy). The mutagenic activities were evaluated with umuC test in presence and in absence of metabolic activation with S9 mix. Then, we used both cytokinesis-blocked micronucleus (CBMN) assay, in combination with fluorescent in situ hybridization (FISH) of human pan-centromeric DNA probes on human lymphocytes in order to evaluate the genotoxic effects. Analysis of all results shows that nitro polycyclic aromatic hydrocarbons (PAHs) are definitely environmental genotoxic/mutagenic hazards and confirms that environmental aromatic nitration reactions lead to an increase in genotoxicity and mutagenicity properties. Particularly 1-NPy and 1,8-DNPy can be considered as human potential carcinogens. They seem to be significant markers of the genotoxicity, mutagenicity, and potential carcinogenicity of complex PAHs mixtures present in traffic emission and industrial environment. In prevention of environmental carcinogenic risk 1-NPy and 1,8-DNPy must therefore be systematically analyzed in environmental complex mixtures in association with combined umuC test, CBMN assay, and FISH on cultured human lymphocytes. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012. Copyright © 2010 Wiley Periodicals, Inc.

Mutagenicity of diesel exhaust particle extracts: influence of fuel composition in two diesel engines

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

Clark, C.R.; Henderson, T.R.; Royer, R.E.

The influence of diesel fuel composition on mutagenicity of exhaust particle associated organic compounds has been investigated using nine fuels varying in aromatic content and distillation properties. The tests were conducted with Oldsmobile Delta-88 and Peugot 504 diesel cars operated according to the EPA Federal Test Procedure. The particulate exhaust from each test was collected on a filter, extracted in dichloromethane and the resulting extract evaluated for mutagenicity in Salmonella strain TA-100. Mutagenicity of extracts of particles collected from the Oldsmobile were highest in the higher aromatic content fuels (greater than 30%) but similar for intermediate (20%) and low (13%)more » aromatic content fuels. No influence of aromaticity on mutagenicity was observed in samples collected from the Peugeot under the same conditions. Thus, fuel aromatic content may enhance the production of mutagenic combustion products at higher concentrations, but may be dependent upon engine type. A good correlation was observed between mutagenicity of the particle extracts and the initial boiling point of the fuel (r . 0.89). Gas chromatography/mass spectrometric analysis of the aromatic fraction of the fuels showed that the fuel producing the most mutagenic combustion products was highest in phenanthrene type compounds.« less

Investigation of repeated dose (90 day) oral toxicity, reproductive/developmental toxicity and mutagenic potential of 'Calebin A'.

PubMed

Majeed, Muhammed; Nagabhushanam, Kalyanam; Natarajan, Sankaran; Bani, Sarang; Pandey, Anjali; Karri, Suresh Kumar

2015-01-01

The present work investigated repeated dose and reproductive toxicity of Calebin A in Wistar rats. A study for assessing the mutagenic potential of Calebin A through an AMES test is also described. Calebin A was orally administered to groups of 10 male and/or 10 female Wistar rats each, assigned to three dose levels (20, 50 and 100 mg/kg/body weight) once daily for 90 consecutive days. None of the animals in any of the treatment/control groups exhibited any abnormal clinical signs/behavioral changes, reproductive as well as developmental parameters, or gross and microscopic changes in both male and female rats. Calebin A was also evaluated for its ability to induce reverse mutations at selected loci of Salmonella typhimurium in the presence and absence of Aroclor 1254 induced rat liver S9 cell lines. In conclusion, 100 mg/kg/d of Calebin A is not likely to produce any significant toxic effects in male and female Wistar rats and no reproductive or developmental toxicity was observed at the same dose and hence Calebin A at 100 mg/kg was determined as "No Observed Adverse Effect Level (NOAEL)" under the test conditions.

Is the Moon Illusion a Celestial Ames Demonstration?

NASA Astrophysics Data System (ADS)

Brecher, Kenneth

2010-01-01

To most naked eye observers, the Moon appears larger when seen near the horizon than it does when seen near the zenith. This "Moon Illusion” has been reported from as early as the fourth century BC and has been the subject of hundreds of papers and two books. Its explanation does not lie in the realm of physics (atmospheric refraction) or astronomy (eccentric lunar orbit) but, rather, in the realm of visual perception. Theories for the cause of the effect abound but, at present, there is no universally accepted explanation. Because the effect can be easily observed in many locations and during the course of an academic year, the moon illusion can provide a nice astronomical example that involves both direct observations and theoretical analysis. As part of the NSF funded "Project LITE: Light Inquiry Through Experiments", we have been developing inexpensive experiments and demonstrations that can be done at home. One of these is a miniature version of the classic "Ames Room". The life size version was originally developed by Adelbert Ames, Jr. and can be seen in many science museums. Our "digital” Ames Room has been designed to be printed on heavy paper using an inexpensive inkjet printer from a PDF file that is posted on the Project LITE web site http://lite.bu.edu and then cut and folded to make the room. When viewed through one wall using a commonly available door viewer, it dramatically demonstrates how the eye and brain system assesses the relative size of objects by making comparisons with the surrounding environment in which the objects are placed. In this presentation we will discuss some insights that the Ames Room provides that may offer clues to the correct explanation for the Moon Illusion. Project LITE is supported by the NSF through DUE Grant # 0715975.

Mutagenicity and human chromosomal effect of stevioside, a sweetener from Stevia rebaudiana Bertoni.

PubMed Central

Suttajit, M; Vinitketkaumnuen, U; Meevatee, U; Buddhasukh, D

1993-01-01

Leaves of Stevia rebaudiana Bertoni have been popularly used as a sweetener in foods and beverages for diabetics and obese people due to their potent sweetener stevioside. In this report, stevioside and steviol were tested for mutagenicity in Salmonella typhimurium strains TA98 and TA100 and for chromosomal effects on cultured human lymphocytes. Stevioside was not mutagenic at concentrations up to 25 mg/plate, but showed direct mutagenicity to only TA98 at 50 mg/plate. However, steviol did not exhibit mutagenicity in either TA98 or TA100, with or without metabolic activation. No significant chromosomal effect of stevioside and steviol was observed in cultured blood lymphocytes from healthy donors (n = 5). This study indicates that stevioside and steviol are neither mutagenic nor clastogenic in vitro at the limited doses; however, in vivo genotoxic tests and long-term effects of stevioside and steviol are yet to be investigated. PMID:8143647

Exposure of pharmacy personnel to mutagenic antineoplastic drugs

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

Nguyen, T.V.; Theiss, J.C.; Matney, T.S.

1981-01-01

The Salmonella reversion test was used to measure the mutagenic activities of urine concentrates from individuals preparing cancer chemotherapy agents for intravenous administration. Longitudinal studies were performed in which the total urine produced in 24 hour periods was collected, starting on a Sunday at 7:00 p.m. after a duty-free weekend and extending over an eight day period. There was no detectable increase in mutagenic activity in the urine concentrates of three pharmacy administrators who had no contact with these drugs. All six individuals admixing drugs in open-faced, horizontal laminar flow hoods displayed a two-fold increase in mutagenesis by the fourthmore » day with peak values of 2.7 to 24-fold occurring on days five and six, reduced values by day seven with a return to the spontaneous level by day eight. When four of the six positive individuals in the preceding experiment admixed comparable amounts of chemotherapeutic drugs in a closed-faced, vertical laminar flow hood, no increase in mutagenic activity was detected in their urine concentrates over the eight day period.« less

A note on the revised galactic neutron spectrum of the Ames collaborative study

NASA Technical Reports Server (NTRS)

Schaefer, H. J.

1980-01-01

Energy distributions of the neutron dose equivalents in the 0.1 to 300 Mev interval for the Ames and Hess spectra are compared. The Ames spectrum shows no evaporation peak, moves the bulk of the flux away from the region of elastic collision and spreads it more evenly over higher energies. The neutron spectrum in space does not seem to hear out the Ames model. Emulsion findings on all manned missions of the past consistently indicate that evaporation events are a prolific source of neutrons in space.

Lack of mutagens in deep-fat-fried foods obtained at the retail level.

PubMed

Taylor, S L; Berg, C M; Shoptaugh, N H; Scott, V N

1982-04-01

The basic methylene chloride extract from 20 of 30 samples of foods fried in deep fat failed to elicit any mutagenic response that could be detected in the Salmonella typhimurium/mammalian microsome assay. The basic extracts of the remaining ten samples (all three chicken samples studied, two of the four potato-chip samples, one of four corn-chip samples, the sample of onion rings, two of six doughnuts, and one of three samples of french-fried potato) showed evidence of weak mutagenic activity. In these samples, amounts of the basic extract equivalent to 28.5-57 g of the original food sample were required to produce revertants at levels of 2.6-4.8 times the background level. Only two of the acidic methylene chloride extracts from the 30 samples exhibited mutagenic activity greater than 2.5 times the background reversion level, and in both cases (one corn-chip and one shrimp sample) the mutagenic response was quite weak. The basic extract of hamburgers fried in deep fat in a home-style fryer possessed higher levels of mutagenic activity (13 times the background reversion level). However, the mutagenic activity of deep-fried hamburgers is some four times lower than that of pan-fried hamburgers.

(New) NASA Administrator Sean O'Keefe comes to Ames for employee briefing and tour. Meets with

NASA Technical Reports Server (NTRS)

2002-01-01

(New) NASA Administrator Sean O'Keefe comes to Ames for employee briefing and tour. Meets with Roberto Cruz, National Hispanic University (seated, right) and Ames Center Director Dr. Henry McDonald follow the signing of the educational MOU between NHU and Ames.

A comparison of mutagen production in fried ground chicken and beef: effect of supplemental creatine.

PubMed

Knize, M G; Shen, N H; Felton, J S

1988-11-01

Ground chicken breast and ground beef with either endogenous or a 10-fold increase in the concentration of creatine were fried at 220 degrees C for 10 min per side. One patty (100 g) of chicken meat yielded 120,000 Salmonella (TA1538) revertants following metabolic activation. The pan residues had 39% of the total activity. Added creatine (10-fold the endogenous level) increased mutagen yields an average of 2-fold. Beef cooked under identical conditions yielded 150,000 revertants/100 g for the meat patties and pan residues combined. Added creatine to beef prior to cooking increased mutagen yields 3-fold. The mutagenic profiles following initial HPLC separation showed that chicken samples with endogenous or added creatine were remarkably similar. Chicken and beef HPLC mutagenicity profiles were also similar to each other, but not identical. This suggests that the general mutagen-forming reactions with the two different types of muscle are qualitatively similar with only minor quantitative differences. The pan residues from both meat types with and without added creatine showed some significant differences in the mutagen peak profile. This work suggests that the types of mutagens formed in chicken are similar to those formed in beef and that creatine appears to be involved in the formation of all the mutagenic compounds produced from fried muscle tissue.

Sperm shape abnormality and urine mutagenicity in mice treated with niclosamide.

PubMed

Vega, S G; Guzmán, P; García, L; Espinosa, J; Cortinas de Nava, C

1988-02-01

Niclosamide, a widely used anthelmintic drug in underdeveloped countries, is known to be mutagenic in the Salmonella typhimurium microsomal test system. The urine obtained from mice treated with niclosamide is mutagenic in the TA98 and TA1538 strains. Its effects on mouse-sperm morphology were evaluated in CD1 and (BALB/cJ x DBA/2J) F1 mice after 5 daily oral niclosamide doses of either 60, 80, 100 or 120 mg/kg. A statistically significant increase in abnormal sperm morphology was detected in both CD1 and (BALB/cJ x DBA/2J) F1 mice. No drug-related effects on testis weight nor on sperm count were observed in either genotype. Urine samples obtained from niclosamide-treated F1 mice were assayed with the Salmonella typhimurium strain TA1538 both in the absence and presence of beta-glucuronidase. In the absence of glucuronidase, urine mutagenicity increased with increasing dose and the highest doses were toxic. In the presence of glucuronidase, urine mutagenicity and toxicity also increased. Only at the highest dose (120 mg/kg), however, was there a positive correlation between the urine mutagenic activity and an increase in the number of abnormal sperm. The results of this study suggest that the increase in abnormal sperm depends on the systemic presence of non-conjugated niclosamide metabolites.

The AME2016 atomic mass evaluation (I). Evaluation of input data; and adjustment procedures

NASA Astrophysics Data System (ADS)

Huang, W. J.; Audi, G.; Wang, Meng; Kondev, F. G.; Naimi, S.; Xu, Xing

2017-03-01

This paper is the first of two articles (Part I and Part II) that presents the results of the new atomic mass evaluation, AME2016. It includes complete information on the experimental input data (also including unused and rejected ones), as well as details on the evaluation procedures used to derive the tables of recommended values given in the second part. This article describes the evaluation philosophy and procedures that were implemented in the selection of specific nuclear reaction, decay and mass-spectrometric results. These input values were entered in the least-squares adjustment for determining the best values for the atomic masses and their uncertainties. Details of the calculation and particularities of the AME are then described. All accepted and rejected data, including outweighted ones, are presented in a tabular format and compared with the adjusted values obtained using the least-squares fit analysis. Differences with the previous AME2012 evaluation are discussed and specific information is presented for several cases that may be of interest to AME users. The second AME2016 article gives a table with the recommended values of atomic masses, as well as tables and graphs of derived quantities, along with the list of references used in both the AME2016 and the NUBASE2016 evaluations (the first paper in this issue). AMDC: http://amdc.impcas.ac.cn/ Contents The AME2016 atomic mass evaluation (I). Evaluation of input data; and adjustment proceduresAcrobat PDF (1.2 MB) Table I. Input data compared with adjusted valuesAcrobat PDF (1.3 MB)

EVALUATION OF NEW 2,2-DIMETHYL-5,5-DIPROPOXYBENZIDINE- AND 3,3-DIPROPOXYBENZIDINE-BASED DIRECT DYE ANALOGS FOR MUTAGENIC ACTIVITY BY USE OF THE SALMONELLA/MAMMALIAN MUTAGENICITY ASSAY

EPA Science Inventory

A series of new metallized and unmetallized direct dyes based on benzidine analogs, 2,2'dimethyl-5,5'-dipropoxybenzidine and 3,3'-dipropoxybenzidine, were evaluated for mutagenicity in Salmonella typhimurium strains TA98 and TA100. All of the dyes examined were judged non-mutagen...

Harrison Ford Tapes Climate Change Show at Ames (Reporter Package)

NASA Image and Video Library

2014-04-11

Hollywood legend Harrison Ford made a special visit to NASA's Ames Research Center to shoot an episode for a new documentary series about climate change called 'Years of Living Dangerously.' After being greeted by Center Director Pete Worden, Ford was filmed meeting with NASA climate scientists and discussed global temperature prediction data processed using one of the world's fastest supercomputers at Ames. Later he flew in the co-pilot seat in a jet used to gather data for NASA air quality studies.

Ames Lab 101: C6: Virtual Engineering

ScienceCinema

McCorkle, Doug

2018-01-01

Ames Laboratory scientist Doug McCorkle explains the importance of virtual engineering and talks about the C6. The C6 is a three-dimensional, fully-immersive synthetic environment residing in the center atrium of Iowa State University's Howe Hall.

Riboregulation of bacterial and archaeal transposition.

PubMed

Ellis, Michael J; Haniford, David B

2016-05-01

The coexistence of transposons with their hosts depends largely on transposition levels being tightly regulated to limit the mutagenic burden associated with frequent transposition. For 'DNA-based' (class II) bacterial transposons there is growing evidence that regulation through small noncoding RNAs and/or the RNA-binding protein Hfq are prominent mechanisms of defense against transposition. Recent transcriptomics analyses have identified many new cases of antisense RNAs (asRNA) that potentially could regulate the expression of transposon-encoded genes giving the impression that asRNA regulation of DNA-based transposons is much more frequent than previously thought. Hfq is a highly conserved bacterial protein that plays a central role in posttranscriptional gene regulation and stress response pathways in many bacteria. Three different mechanisms for Hfq-directed control of bacterial transposons have been identified to date highlighting the versatility of this protein as a regulator of bacterial transposons. There is also evidence emerging that some DNA-based transposons encode RNAs that could regulate expression of host genes. In the case of IS200, which appears to have lost its ability to transpose, contributing a regulatory RNA to its host could account for the persistence of this mobile element in a wide range of bacterial species. It remains to be seen how prevalent these transposon-encoded RNA regulators are, but given the relatively large amount of intragenic transcription in bacterial genomes, it would not be surprising if new examples are forthcoming. WIREs RNA 2016, 7:382-398. doi: 10.1002/wrna.1341 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice

PubMed Central

Csiszar, Anna; Labinskyy, Nazar; Perez, Viviana; Recchia, Fabio A.; Podlutsky, Andrej; Mukhopadhyay, Partha; Losonczy, Gyorgy; Pacher, Pal; Austad, Steven N.; Bartke, Andrzej; Ungvari, Zoltan

2008-01-01

Hypopituitary Ames dwarf mice have low circulating growth hormone (GH)/IGF-I levels, and they have extended longevity and exhibit many symptoms of delayed aging. To elucidate the vascular consequences of Ames dwarfism we compared endothelial O2•− and H2O2 production, mitochondrial reactive oxygen species (ROS) generation, expression of antioxidant enzymes, and nitric oxide (NO) production in aortas of Ames dwarf and wild-type control mice. In Ames dwarf aortas endothelial O2•− and H2O2 production and ROS generation by mitochondria were enhanced compared with those in vessels of wild-type mice. In Ames dwarf aortas there was a less abundant expression of Mn-SOD, Cu,Zn-SOD, glutathione peroxidase (GPx)-1, and endothelial nitric oxide synthase (eNOS). NO production and acetylcholine-induced relaxation were also decreased in aortas of Ames dwarf mice. In cultured wild-type mouse aortas and in human coronary arterial endothelial cells treatment with GH and IGF significantly reduced cellular O2•− and H2O2 production and ROS generation by mitochondria and upregulated expression of Mn-SOD, Cu,Zn-SOD, GPx-1, and eNOS. Thus GH and IGF-I promote antioxidant phenotypic changes in the endothelial cells, whereas Ames dwarfism leads to vascular oxidative stress. PMID:18757483

The AME2016 atomic mass evaluation (II). Tables, graphs and references

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

Wang, Meng; Audi, G.; Kondev, F. G.

This paper is the second part of the new evaluation of atomic masses, Ame2016. Using least-squares adjustments to all evaluated and accepted experimental data, described in Part I, we derive tables with numerical values and graphs to replace those given in Ame2012. The first table lists the recommended atomic mass values and their uncertainties. It is followed by a table of the influences of data on primary nuclides, a table of various reaction and decay energies, and finally, a series of graphs of separation and decay energies. The last section of this paper lists all references of the input datamore » used in the Ame2016 and the Nubase2016 evaluations (first paper in this issue). Amdc: http://amdc.impcas.ac.cn/« less

Ames Lab 101: Ultrafast Magnetic Switching

ScienceCinema

Wang; Jigang

2018-01-01

Ames Laboratory physicists have found a new way to switch magnetism that is at least 1000 times faster than currently used in magnetic memory technologies. Magnetic switching is used to encode information in hard drives, magnetic random access memory and other computing devices. The discovery potentially opens the door to terahertz and faster memory speeds.

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

PubMed

Yamamoto, Akiko; Kohyama, Yuko; Hanawa, Takao

2002-01-01

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

Some innovations and accomplishments of Ames Research Center since its inception

NASA Technical Reports Server (NTRS)

1987-01-01

The innovations and accomplishments of Ames Research Center from 1940 through 1966 are summarized and illustrated. It should be noted that a number of accomplishments were begun at the NASA Dryden Flight Research Facility before that facility became part of the Ames Research Center. Such accomplishments include the first supersonic flight, the first hypersonic flight, the lunar landing research vehicle, and the first digital fly-by-wire aircraft.

TOXICITY REDUCTION EVALUATION (TRE) AT A MUNICIPAL WASTEWATER TREATMENT PLANT USING MUTAGENICITY AS AN END- POINT

EPA Science Inventory

Previous work revealed substantial levels of mutagenicity in effluents from certain municipal wastewater treatment plants. One of these treatment plants was selected for further study to track the effluent mutagenicity to its sources, to chemically characterize the mutagenicity, ...

NASA Ames Fluid Mechanics Laboratory research briefs

NASA Technical Reports Server (NTRS)

Davis, Sanford (Editor)

1994-01-01

The Ames Fluid Mechanics Laboratory research program is presented in a series of research briefs. Nineteen projects covering aeronautical fluid mechanics and related areas are discussed and augmented with the publication and presentation output of the Branch for the period 1990-1993.

Terminal Area ATM Research at NASA Ames

NASA Technical Reports Server (NTRS)

Tobias, Leonard

1997-01-01

The presentation will highlight the following: (1) A brief review of ATC research underway 15 years ago; (2) A summary of Terminal Area ATM Tool Development ongoing at NASA Ames; and (3) A projection of research activities 10-15 years from now.

Application of CFD in aeronautics at NASA Ames Research Center

NASA Astrophysics Data System (ADS)

Maksymiuk, Catherine M.; Enomoto, Francis Y.; Vandalsem, William R.

1995-03-01

The role of Computational Fluid Dynamics (CFD) at Ames Research Center has expanded to address a broad range of aeronautical problems, including wind tunnel support, flight test support, design, and analysis. Balancing the requirements of each new problem against the available resources - software, hardware, time, and expertise - is critical to the effective use of CFD. Several case studies of recent applications highlight the depth of CFD capability at Ames, the tradeoffs involved in various approaches, and lessons learned in the use of CFD as an engineering tool.

Ames Lab 101: Rare-Earth Recycling

ScienceCinema

Ryan Ott

2017-12-22

Recycling keeps paper, plastics, and even jeans out of landfills. Could recycling rare-earth magnets do the same? Perhaps, if the recycling process can be improved. Scientists at the U.S. Department of Energy's Ames Laboratory are working to more effectively remove the neodymium, a rare earth, from the mix of other materials in a magnet.

The AME2016 atomic mass evaluation (I). Evaluation of input data; and adjustment procedures

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

Huang, W. J.; Audi, G.; Wang, Meng

This paper is the first of two articles (Part I and Part II) that presents the results of the new atomic mass evaluation, Ame2016. It includes complete information on the experimental input data (also including unused and rejected ones), as well as details on the evaluation procedures used to derive the tables of recommended values given in the second part. This article describes the evaluation philosophy and procedures that were implemented in the selection of specific nuclear reaction, decay and mass-spectrometric results. These input values were entered in the least-squares adjustment for determining the best values for the atomic massesmore » and their uncertainties. Details of the calculation and particularities of the Ame are then described. All accepted and rejected data, including outweighted ones, are presented in a tabular format and compared with the adjusted values obtained using the least-squares fit analysis. Differences with the previous Ame2012 evaluation are discussed and specific information is presented for several cases that may be of interest to Ame users. The second Ame2016 article gives a table with the recommended values of atomic masses, as well as tables and graphs of derived quantities, along with the list of references used in both the Ame2016 and the Nubase2016 evaluations (the first paper in this issue). Amdc: http://amdc.impcas.ac.cn/« less

Computational Fluid Dynamics Program at NASA Ames Research Center

NASA Technical Reports Server (NTRS)

Holst, Terry L.

1989-01-01

The Computational Fluid Dynamics (CFD) Program at NASA Ames Research Center is reviewed and discussed. The technical elements of the CFD Program are listed and briefly discussed. These elements include algorithm research, research and pilot code development, scientific visualization, advanced surface representation, volume grid generation, and numerical optimization. Next, the discipline of CFD is briefly discussed and related to other areas of research at NASA Ames including experimental fluid dynamics, computer science research, computational chemistry, and numerical aerodynamic simulation. These areas combine with CFD to form a larger area of research, which might collectively be called computational technology. The ultimate goal of computational technology research at NASA Ames is to increase the physical understanding of the world in which we live, solve problems of national importance, and increase the technical capabilities of the aerospace community. Next, the major programs at NASA Ames that either use CFD technology or perform research in CFD are listed and discussed. Briefly, this list includes turbulent/transition physics and modeling, high-speed real gas flows, interdisciplinary research, turbomachinery demonstration computations, complete aircraft aerodynamics, rotorcraft applications, powered lift flows, high alpha flows, multiple body aerodynamics, and incompressible flow applications. Some of the individual problems actively being worked in each of these areas is listed to help define the breadth or extent of CFD involvement in each of these major programs. State-of-the-art examples of various CFD applications are presented to highlight most of these areas. The main emphasis of this portion of the presentation is on examples which will not otherwise be treated at this conference by the individual presentations. Finally, a list of principal current limitations and expected future directions is given.

Briefing to University of Porto on NASA Airborne Science Program and Ames UAVs

NASA Technical Reports Server (NTRS)

Fladeland, Matthew

2015-01-01

NASA Ames is exploring a partnership with the University of Portugal to jointly develop and test new autonomous vehicle technologies. As part of the discussions I will be briefing the University of Portugal faculty on the NASA Airborne Science Program (ASP) and associated activities at NASA Ames Research Center. The presentation will communicate the requirements that drive the program, the assets available to NASA researchers, and discuss research projects that have used unmanned aircraft systems including MIZOPEX, Surprise Valley, and Florida Keys Coral Reef assessment. Other topics will include the SIERRA and Dragon Eye UAV projects operated at Ames.

Air Traffic Management Research at NASA Ames Research Center

NASA Technical Reports Server (NTRS)

Lee, Katharine

2005-01-01

Since the late 1980's, NASA Ames researchers have been investigating ways to improve the air transportation system through the development of decision support automation. These software advances, such as the Center-TRACON Automation System (eTAS) have been developed with teams of engineers, software developers, human factors experts, and air traffic controllers; some ASA Ames decision support tools are currently operational in Federal Aviation Administration (FAA) facilities and some are in use by the airlines. These tools have provided air traffic controllers and traffic managers the capabilities to help reduce overall delays and holding, and provide significant cost savings to the airlines as well as more manageable workload levels for air traffic service providers. NASA is continuing to collaborate with the FAA, as well as other government agencies, to plan and develop the next generation of decision support tools that will support anticipated changes in the air transportation system, including a projected increase to three times today's air-traffic levels by 2025. The presentation will review some of NASA Ames' recent achievements in air traffic management research, and discuss future tool developments and concepts currently under consideration.

Evaluation of Anti-HIV-1 Mutagenic Nucleoside Analogues*

PubMed Central

Vivet-Boudou, Valérie; Isel, Catherine; El Safadi, Yazan; Smyth, Redmond P.; Laumond, Géraldine; Moog, Christiane; Paillart, Jean-Christophe; Marquet, Roland

2015-01-01

Because of their high mutation rates, RNA viruses and retroviruses replicate close to the threshold of viability. Their existence as quasi-species has pioneered the concept of “lethal mutagenesis” that prompted us to synthesize pyrimidine nucleoside analogues with antiviral activity in cell culture consistent with an accumulation of deleterious mutations in the HIV-1 genome. However, testing all potentially mutagenic compounds in cell-based assays is tedious and costly. Here, we describe two simple in vitro biophysical/biochemical assays that allow prediction of the mutagenic potential of deoxyribonucleoside analogues. The first assay compares the thermal stabilities of matched and mismatched base pairs in DNA duplexes containing or not the nucleoside analogues as follows. A promising candidate should display a small destabilization of the matched base pair compared with the natural nucleoside and the smallest gap possible between the stabilities of the matched and mismatched base pairs. From this assay, we predicted that two of our compounds, 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine, should be mutagenic. The second in vitro reverse transcription assay assesses DNA synthesis opposite nucleoside analogues inserted into a template strand and subsequent extension of the newly synthesized base pairs. Once again, only 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine are predicted to be efficient mutagens. The predictive potential of our fast and easy first line screens was confirmed by detailed analysis of the mutation spectrum induced by the compounds in cell culture because only compounds 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine were found to increase the mutation frequency by 3.1- and 3.4-fold, respectively. PMID:25398876

Evaluation of anti-HIV-1 mutagenic nucleoside analogues.

PubMed

Vivet-Boudou, Valérie; Isel, Catherine; El Safadi, Yazan; Smyth, Redmond P; Laumond, Géraldine; Moog, Christiane; Paillart, Jean-Christophe; Marquet, Roland

2015-01-02

Because of their high mutation rates, RNA viruses and retroviruses replicate close to the threshold of viability. Their existence as quasi-species has pioneered the concept of "lethal mutagenesis" that prompted us to synthesize pyrimidine nucleoside analogues with antiviral activity in cell culture consistent with an accumulation of deleterious mutations in the HIV-1 genome. However, testing all potentially mutagenic compounds in cell-based assays is tedious and costly. Here, we describe two simple in vitro biophysical/biochemical assays that allow prediction of the mutagenic potential of deoxyribonucleoside analogues. The first assay compares the thermal stabilities of matched and mismatched base pairs in DNA duplexes containing or not the nucleoside analogues as follows. A promising candidate should display a small destabilization of the matched base pair compared with the natural nucleoside and the smallest gap possible between the stabilities of the matched and mismatched base pairs. From this assay, we predicted that two of our compounds, 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine, should be mutagenic. The second in vitro reverse transcription assay assesses DNA synthesis opposite nucleoside analogues inserted into a template strand and subsequent extension of the newly synthesized base pairs. Once again, only 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine are predicted to be efficient mutagens. The predictive potential of our fast and easy first line screens was confirmed by detailed analysis of the mutation spectrum induced by the compounds in cell culture because only compounds 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine were found to increase the mutation frequency by 3.1- and 3.4-fold, respectively. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

ACTION OF MUTAGENIC AGENTS ON AUXOTROPHIC STRAINS OF STREPTOMYCES

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

Jarai, M.

1962-01-01

The mutagenic effect on Streptomyces auxotrophs of uv and x irradiation and of some chemical agerts was studied. From the observed reverse mutations it was concluded that uv and probably x irradiation have an optimal mutagenic dose. With nine auxotrophic strains it was shown that under the same conditions different gene loci reacted differently to the same mutagenic agent. With uy radiation, mutations occurred most frequently at doses falling within the range of 3500 to 4000 erg/mm/sup 2/. With such doses, the average mutation frequency for singly deficient mutants was 0.8 x 10/sup -6/, for doubly deficient mutants 8.4 xmore » 10/sup -8/. An analysis of the number of mutations as compared to the number of survivors in two biochemical mutants (N-4 and N-11) showed that with N- 4 the highest number of mutations was obtained at doses of 3500 to 4500 erg/mm/ sup 2/, namely, 12 to 15 per 10 surviving conidia, and with strain N-11, the highest frequency was obtained in the same dose range, namely, three to four mutations per 10/sup 6/ surviving conidia. The optimal dose of irradiation corresponds to 90 to 97% lethality. It was shown that, unlike the results with uv irradiation, with x rays no such definite relation existed between optimal dose and frequency of mutations. The highest mutation frequency occurred at doses of 20,000 to 25,000 r, which corresponded to 85 to 91% lethality. Of the chemical substances examined, a definite mutagenic action was exerted by acridine orange, streptomycin, hydroxylamine, phenyl, isocyannte, and 8-quinolinol. The maximum mutagenic frequency for survivors was 41.4 x 10/sup -6/ after uv irradiation (biochemical mutant arg 3-; frequency of sportaneous back mutation, 0.041 x 10/sup -6/). With x irradiation the maximum mutagenic frequency was 3.42 x 10/sup -6/ (biochemical mutant meth 1-; frequency of spontaneous back mutation, 0.28 X 10/sup -6/). With chemical agents the maximum mutation frequencies for the initial conidia number were as

Loss of heterocyclic amine mutagens by insoluble hemicellulose fiber and high-molecular-weight soluble polyphenolics of coffee.

PubMed

Kato, T; Takahashi, S; Kikugawa, K

1991-01-01

The presence of 2 kinds of components in brewed and instant coffee that could remove and destroy heterocyclic amine mutagens was demonstrated. The component that could remove the mutagens was insoluble fiber composed of hemicellulose. The fiber could tightly adsorb the mutagens Trp-P-1, Trp-P-2, Glu-P-1 and A alpha C, and those generated in roasted coffee beans. The component that could destroy the mutagens was high-molecular-weight soluble polyphenolics. They might be converted into quinone derivatives in the presence of molecular oxygen. The quinone derivatives might destroy the mutagens. The fibers and the polyphenolics in one cup of brewed or instant coffee had the capacity to remove and destroy a substantial amount of the mutagens in pyrolysates of foodstuffs.

Synthesis of (±)-Tetrapetalone A-Me Aglycon**

PubMed Central

Carlsen, Peter N.; Mann, Tyler J.; Hoveyda, Amir H.

2014-01-01

The first synthesis of (±)-tetrapetalone A-Me aglycon is described. Key bond-forming reactions include Nazarov cyclization, a ring-closing metathesis (RCM) promoted with complete diastereoselectivity by a chiral Mo-based complex, tandem conjugate reduction-intramolecular aldol cyclization, and oxidative dearomatization. PMID:25045072

URINARY MUTAGENICITY AND COLORECTAL ADENOMA RISK

EPA Science Inventory

Abstract

We investigated urinary mutagenicity and colorectal adenoma risk in a clinic-based, case-control study of currently nonsmoking cases (n = 143) and controls (n = 156). Urinary organics were extracted by C18/methanol from 12-h overnight urine samples, and mutagenici...

Separation of mutagenic components in synthetic crudes

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

Guerin, M. R.; Ho, C. H.; Clark, B. R.

1978-01-01

Mutagenic, basic constituents of a synthetic coal oil and a shale oil were isolated from the crude mixtures. In arriving at an efficient isolation procedure, several liquid chromatographic packing-eluent combinations were tried and the fractions bioassayed to determine the distributions of the mutagenic components. The most effective separation was achieved using a sequential elution scheme with first an alumina-benzene combination followed by a Sephadex LH-20 gel-isopropanol-acetone system. About 75 to 80% of an ether soluble base is eluted with benzene through alumina (activity I). Analysis of this fraction has revealed a wide range of alkyl substituted quinolines and pyridines. Materialmore » remaining on the alumina column was eluted with ethanol, dried and placed on the Sephadex column. Isopropanol (approximately 250 ml) and acetone (approximately 600 ml) were used in that order to elute the material quantitatively. About 12% of the ether-soluble base is eluted with the isopropanol while the rest (approximately 10%) is eluted with the acetone. Additional alkyl pyridine compounds are eluted with isopropanol while the acetone fractions are predominantly multi-ring nitrogen heterocyclic compounds, according to mass spectral analyses. Bioassay data show excellent isolation of the mutagenic activities into the acetone fractions. Negligible activity is found in the sum of the other (90% wt) fractions.« less

(New) NASA Director Sean O'Keefe comes to Ames for employee briefing and tour. Meets with Roberto

NASA Technical Reports Server (NTRS)

2002-01-01

(New) NASA Director Sean O'Keefe comes to Ames for employee briefing and tour. Meets with Roberto Cruz, National Hispanic University (seated, right) and Ames Center Director Dr. Henry McDonald follow the signing of the educational MOU between NHU and Ames.

HAZARD IDENTIFICATION: EFFICIENCY OF SHORT-TERM TESTS IN IDENTIFYING GERM CELL MUTAGENS AND PUTATIVE NONGENOTOXIC CARCINOGENS

EPA Science Inventory

For more than a decade, mutagenicity tests have had a clearly defined role in the identification of potential human mutagens and an ancillary role in the identification of potential human carcinogens. he efficiency of short-term tests in identifying germ cell mutagens has been ex...

A core in vitro genotoxicity battery comprising the Ames test plus the in vitro micronucleus test is sufficient to detect rodent carcinogens and in vivo genotoxins.

PubMed

Kirkland, David; Reeve, Lesley; Gatehouse, David; Vanparys, Philippe

2011-03-18

In vitro genotoxicity testing needs to include tests in both bacterial and mammalian cells, and be able to detect gene mutations, chromosomal damage and aneuploidy. This may be achieved by a combination of the Ames test (detects gene mutations) and the in vitro micronucleus test (MNvit), since the latter detects both chromosomal aberrations and aneuploidy. In this paper we therefore present an analysis of an existing database of rodent carcinogens and a new database of in vivo genotoxins in terms of the in vitro genotoxicity tests needed to detect their in vivo activity. Published in vitro data from at least one test system (most were from the Ames test) were available for 557 carcinogens and 405 in vivo genotoxins. Because there are fewer publications on the MNvit than for other mammalian cell tests, and because the concordance between the MNvit and the in vitro chromosomal aberration (CAvit) test is so high for clastogenic activity, positive results in the CAvit test were taken as indicative of a positive result in the MNvit where there were no, or only inadequate data for the latter. Also, because Hprt and Tk loci both detect gene-mutation activity, a positive Hprt test was taken as indicative of a mouse-lymphoma Tk assay (MLA)-positive, where there were no data for the latter. Almost all of the 962 rodent carcinogens and in vivo genotoxins were detected by an in vitro battery comprising Ames+MNvit. An additional 11 carcinogens and six in vivo genotoxins would apparently be detected by the MLA, but many of these had not been tested in the MNvit or CAvit tests. Only four chemicals emerge as potentially being more readily detected in MLA than in Ames+MNvit--benzyl acetate, toluene, morphine and thiabendazole--and none of these are convincing cases to argue for the inclusion of the MLA in addition to Ames+MNvit. Thus, there is no convincing evidence that any genotoxic rodent carcinogens or in vivo genotoxins would remain undetected in an in vitro test battery

Interrelationships among carcinogenicity, mutagenicity, acute toxicity, and chemical structure in a genotoxicity data base

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

Benigni, R.; Andreoli, C.; Giuliani, A.

1989-01-01

The interrelationships among carcinogenicity, mutagenicity, acute toxicity (LD50), and a number of molecular descriptors were studied by computerized data analysis methods on the data base generated by the International Program for the Evaluation of Short-Term Test for Carcinogens (IPESTTC). With the use of statistical regression methods, three main associations were evidenced: (1) the well-known correlation between carcinogenicity and mutagenicity; (2) a correlation between mutagenicity and toxicity (LD50 ip in mice); and (3) a correlation between toxicity and a recently introduced estimator of the free energy of binding of the molecules to biological receptors. As expected on the basis of themore » large variety of chemical classes represented in the IPESTTC data base, no simple relationship between mutagenicity or carcinogenicity and chemical descriptors was found. To overcome this problem, a new pattern recognition method (REPAD), developed by us for structure-activity studies of noncongeneric chemicals, has been used. This allowed us to highlight a significant difference between the whole patterns of relationships among chemicophysical variables in the two groups to active (mutagenicity and/or carcinogenic) and inactive chemicals. This approach generated a classification rule able to correctly assign about 80% of carcinogens or mutagens.« less

Transformation Systems at NASA Ames

NASA Technical Reports Server (NTRS)

Buntine, Wray; Fischer, Bernd; Havelund, Klaus; Lowry, Michael; Pressburger, TOm; Roach, Steve; Robinson, Peter; VanBaalen, Jeffrey

1999-01-01

In this paper, we describe the experiences of the Automated Software Engineering Group at the NASA Ames Research Center in the development and application of three different transformation systems. The systems span the entire technology range, from deductive synthesis, to logic-based transformation, to almost compiler-like source-to-source transformation. These systems also span a range of NASA applications, including solving solar system geometry problems, generating data analysis software, and analyzing multi-threaded Java code.

NASA AMES Remote Operations Center for 2001

NASA Technical Reports Server (NTRS)

Sims, M.; Marshall, J.; Cox, S.; Galal, K.

1999-01-01

There is a Memorandum of Agreement between NASA Ames, JPL, West Virginia University and University of Arizona which led to funding for the MECA microscope and to the establishment of an Ames facility for science analysis of microscopic and other data. The data and analysis will be by agreement of the Mars Environmental Compatibility Assessment (MECA), Robotic Arm Camera (RAC) and other PI's. This facility is intended to complement other analysis efforts with one objective of this facility being to test the latest information technologies in support of actual mission science operations. Additionally, it will be used as a laboratory for the exploration of collaborative science activities. With a goal of enhancing the science return for both Human Exploration and Development of Space (HEDS) and Astrobiology we shall utilize various tools such as superresolution and the Virtual Environment Vehicle Interface (VEVI) virtual reality visualization tools. In this presentation we will describe the current planning for this facility.

ASSOCIATION BETWEEN URINARY MUTAGENICITY AND RISK OF COLORECTAL ADENOMAS IN A CLINIC-BASED CASE-CONTROL STUDY

EPA Science Inventory

ASSOCIATION BETWEEN URINARY MUTAGENICITY AND RISK OF COLORECTAL ADENOMAS IN A CLINIC-BASED CASE-CONTROL STUDY

Humans are exposed to a variety of mutagens from diet, smoking, or occupation. To explore if exposure to mutagens was related to the risk of colorectal adenomas i...

Antimutagenicity and catechin content of soluble instant teas.

PubMed

Constable, A; Varga, N; Richoz, J; Stadler, R H

1996-03-01

The antimutagenic properties of soluble instant teas were examined using the bacterial Ames assay. Inhibition of the numbers of revertants induced from a number of known mutagens indicates that aqueous extracts of instant teas have antimutagenic activity and antioxidative properties, and can inhibit nitrosation reactions. Despite a significant reduction in the amounts of major green tea catechins, quantified using reversed-phase HPLC with electro-chemical detection, no differences in antimutagenicity were observed between the instant teas, a black fermented tea and a green tea. Oxidation of polyphenolic compounds which occurs during the production of instant tea does not therefore decrease the antioxidant, free radical scavenging and antimutagenic properties. This suggests that catechins are not the only compounds responsible for the protective effects of teas.

MUTAGENIC CHARACTERISTICS OF RIVER WATERS FLOWING THROUGH LARGE METROPOLITAN AREAS IN NORTH AMERICA

EPA Science Inventory

Mutagenic characteristics of river waters flowing through large metropolitan areas in North America

The hanging technique using blue rayon, which specifically adsorbs mutagens with multicyclic planar structures, has the advantages over most conventional methods of not havi...

Ames Lab 101: Real-Time 3D Imaging

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

Zhang, Song

2010-08-02

Ames Laboratory scientist Song Zhang explains his real-time 3-D imaging technology. The technique can be used to create high-resolution, real-time, precise, 3-D images for use in healthcare, security, and entertainment applications.

Ames Lab 101: Real-Time 3D Imaging

ScienceCinema

Zhang, Song

2017-12-22

Ames Laboratory scientist Song Zhang explains his real-time 3-D imaging technology. The technique can be used to create high-resolution, real-time, precise, 3-D images for use in healthcare, security, and entertainment applications.

Mutagenicity and cytoxicity of irradiated foods and food components*

PubMed Central

Schubert, Jack

1969-01-01

The preservation of foods by treatment with ionizing radiation can significantly increase the world's food resources by reducing spoilage and waste. However, irradiation can bring about chemical transformations in food and food components resulting in the formation of potential mutagens, particularly hydrogen peroxide and various organic peroxides. In order to evaluate the safety of irradiated foods for general consumption by the public, and, indeed, the safety of all foods subjected to environmental factors such as food additives, pesticides, drugs, air and water pollutants, etc., it is necessary to supplement the usual feeding tests with procedures designed to detect all classes of genetic damage. This article includes a comprehensive critical review of (1) the experimental evidence relating to the presence of mutagenic and cytotoxic agents in irradiated media, as detected by their effects on mammalian and non-mammalian cells; (2) the chemical changes produced in irradiated media, especially those which produce known mutagenic substances; and (3) new and convenient in vivo methods for the detection and evaluation of genetic damage in mammals. PMID:4908553

Survey of the mutagenicity of surface water, sediments, and drinking water from the Penobscot Indian Nation.

PubMed

Warren, Sarah H; Claxton, Larry D; Diliberto, Janet; Hughes, Thomas J; Swank, Adam; Kusnierz, Daniel H; Marshall, Valerie; DeMarini, David M

2015-02-01

U.S. Environmental Protection Agency (US EPA) Regional Applied Research Effort (RARE) projects address the effects of environmental pollutants in a particular region on the health of the population in that region. This report is part of a RARE project that addresses this for the Penobscot Indian Nation (PIN), Penobscot Island, Maine, U.S., where the Penobscot River has had fish advisories for many years due to high levels of mercury. We used the Salmonella mutagenicity assay with strains TA100, TA98, YG1041, and YG1042 with and without metabolic activation to assess the mutagenic potencies of organic extracts of the Penobscot River water and sediment, as well as drinking-water samples, all collected by the PIN Department of Natural Resources. The source water for the PIN drinking water is gravel-packed groundwater wells adjacent to the Penobscot River. Most samples of all extracts were either not mutagenic or had low to moderate mutagenic potencies. The average mutagenic potencies (revertants/L-equivalent) were 337 for the drinking-water extracts and 177 for the river-water extracts; the average mutagenic potency for the river-sediment extracts was 244 revertants(g-equivalent)(-1). This part of the RARE project showed that extracts of the Penobscot River water and sediments and Penobscot drinking water have little to no mutagenic activity that might be due to the classes of compounds that the Salmonella mutagenicity assay detects, such as polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs (nitroarenes), and aromatic amines. This study is the first to examine the mutagenicity of environmental samples from a tribal nation in the U.S. Published by Elsevier Ltd.

Extending (Q)SARs to incorporate proprietary knowledge for regulatory purposes: A case study using aromatic amine mutagenicity.

PubMed

Ahlberg, Ernst; Amberg, Alexander; Beilke, Lisa D; Bower, David; Cross, Kevin P; Custer, Laura; Ford, Kevin A; Van Gompel, Jacky; Harvey, James; Honma, Masamitsu; Jolly, Robert; Joossens, Elisabeth; Kemper, Raymond A; Kenyon, Michelle; Kruhlak, Naomi; Kuhnke, Lara; Leavitt, Penny; Naven, Russell; Neilan, Claire; Quigley, Donald P; Shuey, Dana; Spirkl, Hans-Peter; Stavitskaya, Lidiya; Teasdale, Andrew; White, Angela; Wichard, Joerg; Zwickl, Craig; Myatt, Glenn J

2016-06-01

Statistical-based and expert rule-based models built using public domain mutagenicity knowledge and data are routinely used for computational (Q)SAR assessments of pharmaceutical impurities in line with the approach recommended in the ICH M7 guideline. Knowledge from proprietary corporate mutagenicity databases could be used to increase the predictive performance for selected chemical classes as well as expand the applicability domain of these (Q)SAR models. This paper outlines a mechanism for sharing knowledge without the release of proprietary data. Primary aromatic amine mutagenicity was selected as a case study because this chemical class is often encountered in pharmaceutical impurity analysis and mutagenicity of aromatic amines is currently difficult to predict. As part of this analysis, a series of aromatic amine substructures were defined and the number of mutagenic and non-mutagenic examples for each chemical substructure calculated across a series of public and proprietary mutagenicity databases. This information was pooled across all sources to identify structural classes that activate or deactivate aromatic amine mutagenicity. This structure activity knowledge, in combination with newly released primary aromatic amine data, was incorporated into Leadscope's expert rule-based and statistical-based (Q)SAR models where increased predictive performance was demonstrated. Copyright © 2016 Elsevier Inc. All rights reserved.

AmeriFlux US-Br1 Brooks Field Site 10- Ames

DOE Data Explorer

Parkin, Tim [USDA; Prueger, John [National Laboratory for Agriculture and the Environment

2016-01-01

This is the AmeriFlux version of the carbon flux data for the site US-Br1 Brooks Field Site 10- Ames. Site Description - The Brooks Field Site 10 - Ames Site is one of three sites (Brooks Field Site 11 and Brooks Field Site 1011) located in a corn/soybean agricultural landscape of central Iowa. The farming systems, associated tillage, and nutrient management practices for soybean/corn production are typical of those throughout Upper Midwest Corn Belt. All three sites are members of the AmeriFlux network. Information for all three can be found in synchronous pages of this website.

AmeriFlux US-Br3 Brooks Field Site 11- Ames

DOE Data Explorer

Parkin, Tim [USDA; Prueger, John [National Laboratory for Agriculture and the Environment

2016-01-01

This is the AmeriFlux version of the carbon flux data for the site US-Br3 Brooks Field Site 11- Ames. Site Description - The Brooks Field Site 11 - Ames Site is one of three sites (Brooks Field Site 10 and Brooks Field Site 1011) located in a corn/soybean agricultural landscape of central Iowa. The farming systems, associated tillage, and nutrient management practices for soybean/corn production are typical of those throughout Upper Midwest Corn Belt. All three sites are members of the AmeriFlux network. Information for all three can be found in synchronous pages of this website.

Mutagenicity of chalks. A case in which the test results led to the improvement of the quality of commercial goods.

PubMed

Hayatsu, H; Ohara, Y; Hayatsu, T; Togawa, K

1983-10-01

Mutagenicity testing, of methanolic extracts of chalks, by the Salmonella/mammalian-microsome system revealed that the blue and the green chalks contained mutagens. A positive mutagenic response was observed on Salmonella typhimurium strain TA98, both in the presence and absence of the microsome system (S9). The source of the mutagenicity was traced to the blue pigment used for manufacturing these chalks. The pigment, copper phthalocyanine, a product of a Japanese chemical industrial company, was found to contain impurities that were mutagenic. The mutagenic principle giving positive response in the TA98 in the presence of S9 was purified 10(5)-fold from the original pigment. Although its structure is yet to be elucidated, this indirect frame-shift mutagen had a strong activity: 5700 His+ revertants per microgram. This information, delivered in the beginning of 1981, prompted the manufacturer to start supplying a mutagen-free product. As a result, the blue chalks on the market became no longer mutagenic in the summer of 1982.

DNA replication after mutagenic treatment in Hordeum vulgare.

PubMed

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

2016-12-01

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

A non-randomized [corrected] controlled trial of the active music engagement (AME) intervention on children with cancer.

PubMed

Robb, Sheri L; Clair, Alicia A; Watanabe, Masayo; Monahan, Patrick O; Azzouz, Faouzi; Stouffer, Janice W; Ebberts, Allison; Darsie, Emily; Whitmer, Courtney; Walker, Joey; Nelson, Kirsten; Hanson-Abromeit, Deanna; Lane, Deforia; Hannan, Ann

2008-07-01

Coping theorists argue that environmental factors affect how children perceive and respond to stressful events such as cancer. However, few studies have investigated how particular interventions can change coping behaviors. The active music engagement (AME) intervention was designed to counter stressful qualities of the in-patient hospital environment by introducing three forms of environmental support. The purpose of this multi-site randomized controlled trial was to determine the efficacy of the AME intervention on three coping-related behaviors (i.e. positive facial affect, active engagement, and initiation). Eighty-three participants, ages 4-7, were randomly assigned to one of three conditions: AME (n = 27), music listening (ML; n = 28), or audio storybooks (ASB; n = 28). Conditions were videotaped to facilitate behavioral data collection using time-sampling procedures. After adjusting for baseline differences, repeated measure analyses indicated that AME participants had a significantly higher frequency of coping-related behaviors compared with ML or ASB. Positive facial affect and active engagement were significantly higher during AME compared with ML and ASB (p<0.0001). Initiation was significantly higher during AME than ASB (p<0.05). This study supports the use of the AME intervention to encourage coping-related behaviors in hospitalized children aged 4-7 receiving cancer treatment. (c) 2007 John Wiley & Sons, Ltd.

Human Robotic Study at Houghton Crater - virtual reality study from NASA Ames (FFC) Future Fight

NASA Technical Reports Server (NTRS)

2002-01-01

Human Robotic Study at Houghton Crater - virtual reality study from NASA Ames (FFC) Future Fight Central simulator tower L-R: Dr Geoffrey Briggs; Jen Jasper (seated); Dr Jan Akins and Mr. Tony Gross, Ames

NASA Ames Science Instrument Launches Aboard New Mars Rover (CheMin)

NASA Image and Video Library

2011-11-23

When NASA's Mars Science Laboratory lands in a region known as Gale Crater in August of 2012, it will be poised to carry out the most sophisticated chemical analysis of the Martian surface to date. One of the 10 instruments on board the rover Curiosity will be CheMin - short for chemistry and mineralogy. Developed by Ames researcher David Blake and his team, it will use new technology to analyze and identify minerals in the Martian rocks and soil. Youtube: NASA Ames Scientists Develop MSL Science Instrument

Positive selection of mutants with deletions of the gal-chl region of the Salmonella chromosome as a screening procedure for mutagens that cause deletions.

PubMed Central

Alper, M D; Ames, B N

1975-01-01

We have developed a convenient and specific positive selection for long deletions through the gal region of the chromosomes of Salmonella typhimurium and Escherichia coli. Through simultaneous selection for mutations in the two closely linked genes, gal and chlA, a variety of deletions of varying length, some extending through as much as 1 min of the chromosome, could be readily obtained. Many of these deletions resulted in the loss of a gene, which we named dhb, concerned with the ability of the bacterium to synthesize the iron chelating agent enterobactin. The selection was adapted for the screening of mutagens for their ability to generate long deletions in the bacterial deoxyribonucleic acid. Forty agents were screened for this capability. Nitrous acid, previously reported to be an efficient mutagen for this purpose, increased the frequency of deletion mutations 50-fold in our system. Three others, nitrogen mustard, mitomycin C, and fast neutrons, were shown to increase the frequency of long deletions between five- and eightfold. The remainder were found to be incapable of generating these deletions. PMID:1090571

A Novel Antifungal Is Active against Candida albicans Biofilms and Inhibits Mutagenic Acetaldehyde Production In Vitro

PubMed Central

Nieminen, Mikko T.; Novak-Frazer, Lily; Rautemaa, Vilma; Rajendran, Ranjith; Sorsa, Timo; Ramage, Gordon; Bowyer, Paul; Rautemaa, Riina

2014-01-01

The ability of C. albicans to form biofilms is a major virulence factor and a challenge for management. This is evident in biofilm-associated chronic oral-oesophageal candidosis, which has been shown to be potentially carcinogenic in vivo. We have previously shown that most Candida spp. can produce significant levels of mutagenic acetaldehyde (ACH). ACH is also an important mediator of candidal biofilm formation. We have also reported that D,L-2-hydroxyisocaproic acid (HICA) significantly inhibits planktonic growth of C. albicans. The aim of the present study was to investigate the effect of HICA on C. albicans biofilm formation and ACH production in vitro. Inhibition of biofilm formation by HICA, analogous control compounds or caspofungin was measured using XTT to measure biofilm metabolic activity and PicoGreen as a marker of biomass. Biofilms were visualised by scanning electron microscopy (SEM). ACH levels were measured by gas chromatography. Transcriptional changes in the genes involved in ACH metabolism were measured using RT-qPCR. The mean metabolic activity and biomass of all pre-grown (4, 24, 48 h) biofilms were significantly reduced after exposure to HICA (p<0.05) with the largest reductions seen at acidic pH. Caspofungin was mainly active against biofilms pre-grown for 4 h at neutral pH. Mutagenic levels (>40 µM) of ACH were detected in 24 and 48 h biofilms at both pHs. Interestingly, no ACH production was detected from D-glucose in the presence of HICA at acidic pH (p<0.05). Expression of genes responsible for ACH catabolism was up-regulated by HICA but down-regulated by caspofungin. SEM showed aberrant hyphae and collapsed hyphal structures during incubation with HICA at acidic pH. We conclude that HICA has potential as an antifungal agent with ability to inhibit C. albicans cell growth and biofilm formation. HICA also significantly reduces the mutagenic potential of C. albicans biofilms, which may be important when treating bacterial-fungal biofilm

Mutagenic effect of extracts from particulate matter collected with sediment traps in the archipelago of Stockholm and the open northern Baltic

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

Broman, D.; Naef, C.; Rannug, U.

The load of various hydrophobic organic compounds (HOCs) on the Baltic Sea aquatic environment is considerable. This investigation samples the water area around Stockholm, of special concern since it is one of the most densely populated urban areas in the Baltic region. Stockholm also houses several power plants, municipal waste incinerators, waste water treatment plants, ports and oil terminals. The runoff from a large lake also passes through the estuarine-like archipelago of Stockholm. Due to the high particulate-water partition coefficients (K[sub p]) of most ecotoxicologically relevant HOCs, particulate matter (PM) becomes very important for occurrence and distribution in the aquaticmore » environment. This PM is the basic food source for important organisms in the benthic, pelagic and littoral parts of the aquatic ecosystem. The load of various HOCs such as petrogenic hydrocarbons (PHCs), various polynuclear aromatic compounds (PACs), and chlorinated hydrocarbons such as polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in association with PM in the aquatic environment of the Stockholm area is well documented. However, the ecotoxicological relevance of organic extracts of PM, including the above identified compounds and various unidentified HOCs, is not fully evaluated. To evaluate the genotoxic potential of extracts of PM, collected with sediment traps in the Stockholm water area and in the open northern Baltic, we used the Ames test on Salmonella typhimurium strain TA100, with and without a metabolizing system. After extraction and before the mutagenicity tests all PM samples were fractionated on an HPLC-system into three fractions containing aliphatic/monoaromatic-, diaromatic, (containing, e.g., PCDD/Fs and PCBs) and polyaromatic compounds (containing various PACs). The relative mutagenic potential of these fractions at the different sediment trap sampling stations are discussed and evaluated. 13 refs., 1

Evaluating Fatigue in Operational Settings: The NASA Ames Fatigue Countermeasures Program

NASA Technical Reports Server (NTRS)

Rosekind, Mark R.; Gregory, Kevin; Miller, Donna; Webbon, Lissa; Oyung, Ray

1996-01-01

In response to a 1980 Congressional request, NASA Ames initiated a program to examine fatigue in flight operations. The Program objectives are to examine fatigue, sleep loss, and circadian disruption in flight operations, determine the effects of these factors on flight crew performance, and the development of fatigue countermeasures. The NASA Ames Fatigue Countermeasures Program conducts controlled laboratory experiments, full-mission flight simulations, and field studies. A range of subjective, behavioral, performance, physiological, and environmental measures are used depending on study objectives. The Program has developed substantial expertise in gathering data during actual flight operations and in other work settings. This has required the development of ambulatory and other measures that can be carried throughout the world and used at 41,000 feet in aircraft cockpits. The NASA Ames Fatigue Countermeasures Program has examined fatigue in shorthaul, longhaul, overnight cargo, and helicopter operations. A recent study of planned cockpit rest periods demonstrated the effectiveness of a brief inflight nap to improve pilot performance and alertness. This study involved inflight reaction time/vigilance performance testing and EEG/EOG measures of physiological alertness. The NASA Ames Fatigue Countermeasures Program has applied scientific findings to the development of education and training materials on fatigue countermeasures, input to federal regulatory activities on pilot flight, duty, and rest requirements, and support of National Transportation Safety Board accident investigations. Current activities are examining fatigue in nonaugmented longhaul flights, regional/commuter flight operations, corporate/business aviation, and psychophysiological variables related to performance.

Intoxication-Related AmED (Alcohol Mixed with Energy Drink) Expectancies Scale: Initial Development and Validation

PubMed Central

Miller, Kathleen E.; Dermen, Kurt H.; Lucke, Joseph F.

2017-01-01

BACKGROUND Young adult use of alcohol mixed with energy drinks (AmEDs) has been linked with elevated risks for a constellation of problem behaviors. These risks may be conditioned by expectancies regarding the effects of caffeine in conjunction with alcohol consumption. The aim of this study was to describe the construction and psychometric evaluation of the Intoxication-Related AmED Expectancies Scale (AmED_EXPI), 15 self-report items measuring beliefs about how the experience of AmED intoxication differs from the experience of noncaffeinated alcohol (NCA) intoxication. METHODS Scale development and testing were conducted using data from a U.S. national sample of 3,105 adolescents and emerging adults aged 13–25. Exploratory and confirmatory factor analyses were conducted to evaluate the factor structure and establish factor invariance across gender, age, and prior experience with AmED use. Cross-sectional and longitudinal analyses examining correlates of AmED use were used to assess construct and predictive validity. RESULTS In confirmatory factor analyses, fit indices for the hypothesized four-factor structure (i.e., Intoxication Management [IM], Alertness [AL], Sociability [SO], and Jitters [JT]) revealed a moderately good fit to the data. Together, these factors accounted for 75.3% of total variance. The factor structure was stable across male/female, teen/young adult, and AmED experience/no experience subgroups. The resultant unit-weighted subscales showed strong internal consistency and satisfactory convergent validity. Baseline scores on the IM, SO, and JT subscales predicted changes in AmED use over a subsequent three-month period. CONCLUSIONS The AmED_EXPI appears to be a reliable and valid tool for measuring expectancies about the effects of caffeine during alcohol intoxication. PMID:28421613

Toxicological and mutagenic analysis of Artemisia dracunculus (tarragon) extract.

PubMed

Kalantari, Heibatullah; Galehdari, Hamid; Zaree, Zahra; Gesztelyi, Rudolf; Varga, Balazs; Haines, David; Bombicz, Mariann; Tosaki, Arpad; Juhasz, Bela

2013-01-01

Mutagenicity and liver toxicity of the herb tarragon (Artemisia dracunculus) were evaluated using single cell gel (comet) electrophoresis. Ten microlitres aliquots of peripheral venous human blood were incubated with tarragon extract, saline, or the mutagen sodium dichromate. Cell suspensions dispersed in low-melting agarose were electrophoresed in ethidium bromide. The resulting DNA migration trails were obtained using fluorescent microscopy at 400× magnification, and graded according to the mutagenicity index (MI) for each cell incubation condition. The in vivo liver toxicity of Artemisia dracunculus was assessed in the blood of mice treated orally with the extract of the herb, using alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as liver function indicators. Liver morphology was assessed using hematoxylin and eosin (HE) staining of liver tissue. The present study demonstrated a direct correlation between tarragon extract dosage and three major outcome variables: MI; serum liver enzyme activity; and liver histopathology. These outcomes are possibly due to the presence in tarragon of methylchavicol and other genotoxic compounds. These findings provide a preliminary guide for risk assessment of tarragon in diet and in possible therapeutic applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

Selected Topics in Overset Technology Development and Applications At NASA Ames Research Center

NASA Technical Reports Server (NTRS)

Chan, William M.; Kwak, Dochan (Technical Monitor)

2002-01-01

This paper presents a general overview of overset technology development and applications at NASA Ames Research Center. The topics include: 1) Overview of overset activities at NASA Ames; 2) Recent developments in Chimera Grid Tools; 3) A general framework for multiple component dynamics; 4) A general script module for automating liquid rocket sub-systems simulations; and 5) Critical future work.

Bioassay-directed fractionation and salmonella mutagenicity of automobile and forklift diesel exhaust particles.

PubMed Central

DeMarini, David M; Brooks, Lance R; Warren, Sarah H; Kobayashi, Takahiro; Gilmour, M Ian; Singh, Pramila

2004-01-01

Many pulmonary toxicity studies of diesel exhaust particles (DEPs) have used an automobile-generated sample (A-DEPs) whose mutagenicity has not been reported. In contrast, many mutagenicity studies of DEPs have used a forklift-generated sample (SRM 2975) that has been evaluated in only a few pulmonary toxicity studies. Therefore, we evaluated the mutagenicity of both DEPs in Salmonella coupled to a bioassay-directed fractionation. The percentage of extractable organic material (EOM) was 26.3% for A-DEPs and 2% for SRM 2975. Most of the A-EOM (~55%) eluted in the hexane fraction, reflecting the presence of alkanes and alkenes, typical of uncombusted fuel. In contrast, most of the SRM 2975 EOM (~58%) eluted in the polar methanol fraction, indicative of oxygenated and/or nitrated organics derived from combustion. Most of the direct-acting, base-substitution activity of the A-EOM eluted in the hexane/dichloromethane (DCM) fraction, but this activity eluted in the polar methanol fraction for the SRM 2975 EOM. The direct-acting frameshift mutagenicity eluted across fractions of A-EOM, whereas > 80% eluted only in the DCM fraction of SRM 2975 EOM. The A-DEPs were more mutagenic than SRM 2975 per mass of particle, having 227 times more polycyclic aromatic hydrocarbon-type and 8-45 more nitroarene-type mutagenic activity. These differences were associated with the different conditions under which the two DEP samples were generated and collected. A comprehensive understanding of the mechanisms responsible for the health effects of DEPs requires the evaluation of DEP standards for a variety of end points, and our results highlight the need for multidisciplinary studies on a variety of representative samples of DEPs. PMID:15175166

Emission of polycyclic aromatic hydrocarbons, toxicity, and mutagenicity from domestic cooking using sawdust briquettes, wood, and kerosene.

PubMed

Kim, OanhNguyenThi; Nghiem, Le Hoang; Phyu, Yin Latt

2002-03-01

Smoke samples, in both gas and particulate matter (PM) phases, of the three domestic stoves were collected using U.S. EPA modified method 5 and were analyzed for 17 PAH (HPLC-UV), acute toxicity (Microtox test), and mutagenicity (Amestest). The gas phase of smoke contributed > or = 95% of 17 PAH, > or = 96% of toxicity, and > or = 60% of mutagenicity. The highest emission factor of 17 PAH was from sawdust briquettes (260 mg/kg), but the highest emission of 11 genotoxic PAH was from kerosene (28 mg/kg). PM samples of kerosene smoke were not toxic. The total toxicity emission factor was the highest from sawdust, followed by kerosene and wood fuel. Smoke samples from the kerosene stove were not mutagenic. TA98 indicated the presence of both direct and indirect mutagenic activities in PM samples of sawdust and wood fuel but only direct mutagenic activities in the gas phase. TA100 detected only direct mutagenic activities in both PM and gas-phase samples. The higher mutagenicity emission factor was from wood fuel, 12 x 10(6) revertants/kg (TA100-S9) and 3.5 x 10(6) (TA98-S9), and lower from sawdust, 2.9 x 10(6) (TA100-S9) and 2.8 x 10(6) (TA98-S9). The low burning rate and high efficiency of a kerosene stove have resulted in the lowest PAH, toxicity, and mutagenicity emissions from daily cooking activities. The bioassays produced toxicity and mutagenicity results in correspondence with the PAH content of samples. The tests could be used for a quick assessment of potential health risks.

Antimutagenicity of Methanolic Extracts from Anemopsis californica in Relation to Their Antioxidant Activity

PubMed Central

Del-Toro-Sánchez, Carmen Lizette; Bautista-Bautista, Nereyda; Blasco-Cabal, José Luis; Gonzalez-Ávila, Marisela; Gutiérrez-Lomelí, Melesio; Arriaga-Alba, Myriam

2014-01-01

Anemopsis californica has been used empirically to treat infectious diseases. However, there are no antimutagenic evaluation reports on this plant. The present study evaluated the antioxidant activity in relation to the mutagenic and antimutagenic activity properties of leaf (LME) and stem (SME) methanolic extracts of A. californica collected in the central Mexican state of Querétaro. Antioxidant properties and total phenols of extracts were evaluated using DPPH (1,1-diphenyl-2-picrylhydrazyl) and Folin-Ciocalteu methods, respectively. Mutagenicity was evaluated using the Ames test employing Salmonella enterica serovar Typhimurium strains (TA98, TA100, and TA102), with and without an aroclor 1254 (S9 mixture). Antimutagenesis was performed against mutations induced on the Ames test with MNNG, 2AA, or 4NQO. SME presented the highest antioxidant capacity and total phenolic content. None of the extracts exhibited mutagenicity in the Ames test. The extracts produced a significant reduction in 2AA-induced mutations in S. typhimurium TA98. In both extracts, mutagenesis induced by 4NQO or methyl-N′-nitro-N-nitrosoguanidine (MNNG) was reduced only if the exposure of strains was <10 μg/Petri dish. A. californca antioxidant properties and its capacity to reduce point mutations render it suitable to enhance medical cancer treatments. The significant effect against antimutagenic 2AA suggests that their consumption would provide protection against carcinogenic polycyclic aromatic compounds. PMID:25152760

Absence of genotoxic effects of the chalcone (E)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one) and its potential chemoprevention against DNA damage using in vitro and in vivo assays

PubMed Central

2017-01-01

The chalcone (E)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one), or 2HMC, displays antileishmanial, antimalarial, and antioxidant activities. The aim of this study was to investigate the cytotoxic, genotoxic, mutagenic, and protective effects of 2HMC using the Ames mutagenicity test, the mouse bone marrow micronucleus test, and the comet assay in mice. In the assessment using the Ames test, 2HMC did not increase the number of His+ revertants in Salmonella typhimurium strains, demonstrating lack of mutagenicity. 2HMC showed no significant increase in micronucleated polychromatic erythrocyte frequency (MNPCE) in the micronucleus test, or in DNA strand breaks using the comet assay, evidencing absence of genotoxicity. Regarding cytotoxicity, 2HMC exhibited moderate cytotoxicity in mouse bone marrow cells by micronucleus test. 2HMC showed antimutagenic action in co-administration with the positive controls, sodium azide (SA) and 4-nitroquinoline-1-oxide (4NQO), in the Ames test. Co-administered and mainly pre-administered with cyclophosphamide (CPA), 2HMC caused a decrease in the frequency of MNPCE using the micronucleus test and in DNA strand breaks using the comet assay. Thus, 2HMC exhibited antimutagenic and antigenotoxic effects, displaying a DNA-protective effect against CPA, SA, and 4NQO carcinogens. In conclusion, 2HMC presented antimutagenic, antigenotoxic and moderate cytotoxic effects; therefore it is a promising molecule for cancer prevention. PMID:28207781

Absence of genotoxic effects of the chalcone (E)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one) and its potential chemoprevention against DNA damage using in vitro and in vivo assays.

PubMed

Lima, Débora Cristina da Silva; Vale, Camila Regina do; Véras, Jefferson Hollanda; Bernardes, Aline; Pérez, Caridad Noda; Chen-Chen, Lee

2017-01-01

The chalcone (E)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one), or 2HMC, displays antileishmanial, antimalarial, and antioxidant activities. The aim of this study was to investigate the cytotoxic, genotoxic, mutagenic, and protective effects of 2HMC using the Ames mutagenicity test, the mouse bone marrow micronucleus test, and the comet assay in mice. In the assessment using the Ames test, 2HMC did not increase the number of His+ revertants in Salmonella typhimurium strains, demonstrating lack of mutagenicity. 2HMC showed no significant increase in micronucleated polychromatic erythrocyte frequency (MNPCE) in the micronucleus test, or in DNA strand breaks using the comet assay, evidencing absence of genotoxicity. Regarding cytotoxicity, 2HMC exhibited moderate cytotoxicity in mouse bone marrow cells by micronucleus test. 2HMC showed antimutagenic action in co-administration with the positive controls, sodium azide (SA) and 4-nitroquinoline-1-oxide (4NQO), in the Ames test. Co-administered and mainly pre-administered with cyclophosphamide (CPA), 2HMC caused a decrease in the frequency of MNPCE using the micronucleus test and in DNA strand breaks using the comet assay. Thus, 2HMC exhibited antimutagenic and antigenotoxic effects, displaying a DNA-protective effect against CPA, SA, and 4NQO carcinogens. In conclusion, 2HMC presented antimutagenic, antigenotoxic and moderate cytotoxic effects; therefore it is a promising molecule for cancer prevention.

The strains recommended for use in the bacterial reverse mutation test (OECD guideline 471) can be certified as non-genetically modified organisms.

PubMed

Sugiyama, Kei-Ichi; Yamada, Masami; Awogi, Takumi; Hakura, Atsushi

2016-01-01

The bacterial reverse mutation test, commonly called Ames test, is used worldwide. In Japan, the genetically modified organisms (GMOs) are regulated under the Cartagena Domestic Law, and organisms obtained by self-cloning and/or natural occurrence would be exempted from the law case by case. The strains of Salmonella typhimurium and Escherichia coli recommended for use in the bacterial reverse mutation test (OECD guideline 471), have been considered as non-GMOs because they can be constructed by self-cloning or naturally occurring bacterial strains, or do not disturb the biological diversity. The present article explains the reasons why these tester strains should be classified as non-GMOs.

(New) NASA Administrator Sean O'Keefe comes to Ames for employee briefing and tour. Meets with

NASA Technical Reports Server (NTRS)

2002-01-01

(New) NASA Administrator Sean O'Keefe comes to Ames for employee briefing and tour. Meets with Roberto Cruz, National Hispanic University (left) at Amesto sign the educational MOU between NHU and Ames.

EFFECT OF THE DECHLORINATING AGENT, ASCORBIC ACID, ON THE MUTAGENICITY OF CHLORINATED WATER SAMPLES

EPA Science Inventory

XAD resin adsorption has been widely used to concentrate the organic compounds present in chlorinated drinking waters prior to mutagenicity testing. Previous work has shown that mutagenic artifcats can arise due to the reaction of residual chlorine with the resins. Althrough the ...

History of the science of mutagenesis from a personal perspective.

PubMed

Malling, Heinrich V

2004-01-01

A career in the study of mutagenesis spanning 50 years is a gift few scientists have been bestowed. My tenure in the field started in 1953, the year the structure of DNA became known (Watson and Crick [1953]: Nature 171:737). Before that time, it was suspected that DNA was the genetic material based on the research of Oswald T. Avery (Avery et al. [1944]: J Exp Med 79:137), but many scientists still believed that proteins or polysaccharides could be the genetic material. The present article describes a lifetime of personal experience in the field of chemical mutagenesis. The methods used to treat viruses with chemical mutagens were well developed in the 1950s. Here I review the early use of nitrous acid and hydroxylamine as mutagens in eukaryotes, the development of methods for the metabolic activation of mutagens by microsomal preparations, and the selection of a mutant tester set for the qualitative characterization of the mutagenic activity of chemicals. These studies provided critical background information that was used by Bruce Ames in the development of his Salmonella/microsome assay, widely known as the Ames test (Ames et al. [1973]: Proc Nat Acad Sci USA 70:2281-2285). This article also describes how a set of diagnostic chemical mutagens was selected and used to identify the molecular nature of gene mutations. Today, DNA sequencing has replaced the use of diagnostic mutagens, but studies of this kind formed the foundation of modern mutation research. They also helped set the stage for the organization of the Environmental Mutagen Society and the Environmental Mutagen Information Center, which are described. The article ends with the development of mammalian single-cell mutation assays, the first system for studying in vivo mutagenesis using recoverable vectors in transgenic animals, other mutation assays in intact mammals, and my thoughts on the critically important area of germ cell mutagenesis. This narrative is not a complete autobiographical account

Evaluation of mutagenic and antimutagenic activities of oligorutin and oligoesculin.

PubMed

Ben Rhouma, Ghada; Chebil, Latifa; Krifa, Mounira; Ghoul, Mohamed; Chekir-Ghedira, Leila

2012-12-01

Rutin and esculin have been polymerised by laccase. Five fractions with M(w)¯ between 2127.42 and 8331.85g/mol for oligorutins, and between 688.12 and 6973g/mol for oligoesculins, were obtained. Fourier transformed infrared analysis showed that oligorutins were formed through C-C, C-O and CO linkages, while oligoesculins were obtained through C-C linkages. Monomers, their oligomers and their metabolites exhibited no mutagenic effect. Oligorutins and oligoesculins were more efficient in reducing the mutagenicity of methyl methanesulphonate, by, respectively, 69% and 64.8% in the presence of Salmonella typhimurium TA104, and 79.7% and 68.9% in the presence of S. typhimurium TA102, than were their monomers. The same oligomers revealed greater significant inhibitory effect of 2-aminoanthracene mutagenicity (respectively 82.4% and 79.3% in the presence of S. typhimurium TA104, and 89.2% and 82.9% in the presence of S. typhimurium TA102), than their monomers. Our results strongly suggest the enhancement of the tested monomer antimutagenicity after polymerisation. Copyright © 2012 Elsevier Ltd. All rights reserved.

The 1994 Ames Research Center publications: A bibliography

NASA Technical Reports Server (NTRS)

Scarich, Shelley J. (Editor)

1995-01-01

This document is a compilation of the scientific and technical information that Ames Research Center has produced during the calendar year 1994. Included are citations for formal reports, high-number conference publications, high-number technical memorandums, contractor reports, journal articles, meeting presentation, tech briefs, patents, and translations.

A reaction mechanism-based prediction of mutagenicity: α-halo carbonyl compounds adduct with DNA by SN2 reaction.

PubMed

Haranosono, Yu; Ueoka, Hiroki; Kito, Gakushi; Nemoto, Shingo; Kurata, Masaaki; Sakaki, Hideyuki

2018-01-01

Most of the α-halo carbonyl (AHC) compounds tend to be predicted as mutagenic by structure-activity relationship based on structural category only, because they have an alkyl halide structure as a structural alert of mutagenicity. However, some AHC compounds are not mutagenic. We hypothesized that AHC reacts with DNA by S N 2 reaction, and the reactivity relates to mutagenicity. As an index of S N 2 reactivity, we focused on molecular orbitals (MOs), as the direction and position of two molecules in collision are important in the S N 2 reaction. The MOs suitable for S N 2 reaction (SN2MOs) were selected by chemical-visual inspection based on the shape of the MO. We used the level gap and the energy gap between SN2MO and the lowest unoccupied molecular orbital as the descriptors of S N 2 reactivity. As the results, S N 2 reactivity related to mutagenicity and we were able to predict mutagenicity of 20 AHC compounds with 95.0% concordance. It was suggested that S N 2 reaction is a reaction mechanism of AHC compounds and DNA in the mutagenic process. The method allows for discrimination among structurally similar compounds by combination with quantitative structure-activity relationships. The combination approach is expected to be useful for the mutagenic assessment of pharmaceutical impurities.

OVERVIEW OF THE MUTAGENICITY OF URBAN AIR

EPA Science Inventory

For the past 25 years, there has been great interest in the mutagenicity and carcinogenicity of ambient air and in the sources of those genotoxicants. Prior to the 1980's, the evaluation of airborne toxicants was done on a pollutant-by-pollutant basis. However, the assessment of ...

Ames Research Center Publications: A Continuing Bibliography

NASA Technical Reports Server (NTRS)

1981-01-01

The Ames Research Center Publications: A Continuing Bibliography contains the research output of the Center indexed during 1981 in Scientific and Technical Aerospace Reports (STAR), Limited Scientific and Technical Aerospace Reports (LSTAR), International Aerospace Abstracts (IAA), and Computer Program Abstracts (CPA). This bibliography is published annually in an attempt to effect greater awareness and distribution of the Center's research output.

Cell-Based Genotoxicity Testing

NASA Astrophysics Data System (ADS)

Reifferscheid, Georg; Buchinger, Sebastian

Genotoxicity test systems that are based on bacteria display an important role in the detection and assessment of DNA damaging chemicals. They belong to the basic line of test systems due to their easy realization, rapidness, broad applicability, high sensitivity and good reproducibility. Since the development of the Salmonella microsomal mutagenicity assay by Ames and coworkers in the early 1970s, significant development in bacterial genotoxicity assays was achieved and is still a subject matter of research. The basic principle of the mutagenicity assay is a reversion of a growth inhibited bacterial strain, e.g., due to auxotrophy, back to a fast growing phenotype (regain of prototrophy). Deeper knowledge of the ­mutation events allows a mechanistic understanding of the induced DNA-damage by the utilization of base specific tester strains. Collections of such specific tester strains were extended by genetic engineering. Beside the reversion assays, test systems utilizing the bacterial SOS-response were invented. These methods are based on the fusion of various SOS-responsive promoters with a broad variety of reporter genes facilitating numerous methods of signal detection. A very important aspect of genotoxicity testing is the bioactivation of ­xenobiotics to DNA-damaging compounds. Most widely used is the extracellular metabolic activation by making use of rodent liver homogenates. Again, genetic engineering allows the construction of highly sophisticated bacterial tester strains with significantly enhanced sensitivity due to overexpression of enzymes that are involved in the metabolism of xenobiotics. This provides mechanistic insights into the toxification and detoxification pathways of xenobiotics and helps explaining the chemical nature of hazardous substances in unknown mixtures. In summary, beginning with "natural" tester strains the rational design of bacteria led to highly specific and sensitive tools for a rapid, reliable and cost effective �

The mutagenicities of safrole, estragole, eugenol, trans-anethole, and some of their known or possible metabolites for Salmonella typhimurium mutants.

PubMed

Swanson, A B; Chambliss, D D; Blomquist, J C; Miller, E C; Miller, J A

1979-04-01

Safrole, estragole, anethole, and eugenol and some of their known or possible metabolites were tested for mutagenic activity for S. typhimurium TA1535, TA100, and TA98. Highly purified 1'-hydroxyestragole and 1'-hydroxysafrole were mutagenic (approximately 15 and 10 revertants/micromole, respectively) for strain TA100 in the absence of fortified liver microsomes; trans-anethole and estragole appeared to have very weak activity. 3'-Hydroxyanethole was too toxic for an adequate test. Supplementation with NADPH-fortified rat-liver microsomes and cytosol converted 3'-hydroxyanethole to a mutagen(s) and increased the mutagenic activities for strain TA100 of 1'-hydroxyestragole, 1'-hydroxysafrole, estragole, and anethole. No mutagenicity was detected for safrole or eugenol with or without added NADPH-fortified liver preparations. The electrophilic 2',3'-oxides of safrole, 1'-hydroxysafrole, 1'-acetoxysafrole, 1'-oxosafrole, estragole, 1'-hydroxyestragole, and eugenol showed dose-dependent mutagenic activities for strain TA1535 in the absence of fortified liver microsomes. These mutagenic activities ranged from about 330 revertants/micromole for 1'-oxosafrole-2',3'-oxide to about 7000 revertants/micromole for safrole-2',3'-oxide. The arylalkenes, their hydroxylated derivatives, or their epoxides did not show mutagenic activity for strain TA98, except for 1'-oxosafrole-2',3'-oxide, which had weak activity. Since the arylalkenes are hydroxylated and/or epoxidized by hepatic microsomes, hydroxy and epoxide derivatives appear to be proximate and ultimate mutagenic metabolites, respectively, of the arylalkenes.

Spectroscopic characterization and biological studies in vitro of a new silver complex with furosemide: Prospective of application as an antimicrobial agent

NASA Astrophysics Data System (ADS)

Lustri, Wilton R.; Lazarini, Silmara C.; Lustri, Bruna Cardinali; Corbi, Pedro P.; Silva, Maria Aline C.; Resende Nogueira, Flávia Aparecida; Aquino, Renata; Amaral, André C.; Treu Filho, Oswaldo; Massabni, Antonio Carlos; da Silva Barud, Hernane

2017-04-01

The present article describes the synthesis and biological studies in vitro of a novel silver complex with furosemide (Ag-FSE). Elemental, thermal and mass spectrometric analysis indicated a 1:1 metal/ligand composition, with the molecular formula AgC12H10ClN2O5S. Infrared and nuclear magnetic resonance studies suggest coordination of the ligand to the silver ion by the oxygen atoms of the carboxylate group. Additional Density Functional Theory (DFT) studies led to the proposition of the structure of the Ag-FSE complex. The antibacterial activities of the complex were primarily evaluated by antibiogram assays using the disc diffusion method and minimum inhibitory concentrations (MIC). Moreover, the mutagenicity of the complex was also evaluated to ensure that it is safe for subsequent application. The Ag-FSE complex has shown a significant in vitro antibacterial activity against Gram-positive Staphylococcus aureus (ATCC 25923), Gram negative Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853), and yeast Candida albicans (ATCC 90028). The absence of a mutagenic activity of Ag-FSE against Salmonella Typhimurium bacterial strains in the Ames assay is an extremely important finding for its future use as a drug in medicine.

Ames Research Center Publications, July 1971 through December 1973

NASA Technical Reports Server (NTRS)

1975-01-01

A bibliography of the publications of Ames Research Center authors and contractors which appeared as formal NASA publications, journal articles, books, chapters of books, patents, and contractor reports is presented. Years covered are July 1971 through December 1973.

NASA Ames Sonic Boom Testing

NASA Technical Reports Server (NTRS)

Durston, Donald A.; Kmak, Francis J.

2009-01-01

Multiple sonic boom wind tunnel models were tested in the NASA Ames Research Center 9-by 7-Foot Supersonic Wind Tunnel to reestablish related test techniques in this facility. The goal of the testing was to acquire higher fidelity sonic boom signatures with instrumentation that is significantly more sensitive than that used during previous wind tunnel entries and to compare old and new data from established models. Another objective was to perform tunnel-to-tunnel comparisons of data from a Gulfstream sonic boom model tested at the NASA Langley Research Center 4-foot by 4-foot Unitary Plan Wind Tunnel.

Mutagenic activities of heterocyclic amines in Chinese hamster lung cells in culture

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

Terada, M.; Nagao, M.; Nakayasu, M.

1986-01-01

A mutation assay system with Chinese hamster lung cells (CHL) using diphtheria toxin resistance as a selective marker has been established. The mutagenic activities of heterocyclic amines, originally isolated from pyrolyzates of amino acids and proteins, broiled fish and fried beef were assayed in cultured CHL cells in the absence and presence of a metabolic activation system, with diphtheria toxin resistance as a marker. All the heterocyclic amines tested except 3-amino-1,4-dimethyl-5H-pyrido (4,3-b)indole (Trp-P-1) required the presence of a metabolic activation system for mutagenicity on CHL cells. 3-Amino-1-methyl-5H-pyrido(4,3-b)indole (Trp-P-2) was the most mutagenic among the heterocyclic amines tested. Other compounds weremore » also mutagenic in the following order of decreasing potency: Trp-P-1, 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ), 2-amino-3-methylimidazo(4,5-f)quinoline (IQ), 2-amino-9H-pyrido(2,3-b)indole (A..cap alpha..C), 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx), 2-amino-6-methyldipyrido(1,2-a:3',2'-d)imidazole (Glu-P-1) and 2-aminodipyrido(1,2--a:3',2'-d)imidazole (Glu-P-2).« less

Mutagens in urine of non-smoking and smoking workers in an aircraft tyre retreading plant. Skin exposure as a causal factor?

PubMed

Bos, R P; Kromhout, H; Ikink, H; de Haan, W; Koppejan, J; Theuws, J L

1989-05-01

In an aircraft type retreading plant environmental samples taken at several departments showed mutagenic properties. Thursday urine samples of non-smoking and smoking workers showed higher urinary mutagenicity than urine samples collected on Sundays, thus suggesting occupational exposure to mutagenic substances. A relation between urinary mutagenicity on Thursdays and skin contamination measured on Wednesdays was observed. The data suggest that intake through the skin plays an important role in the occupational exposure to mutagenic compounds of rubber workers.

Oxygen radical-mediated mutagenic effect of asbestos on human lymphocytes: suppression by oxygen radical scavengers.

PubMed

Korkina, L G; Durnev, A D; Suslova, T B; Cheremisina, Z P; Daugel-Dauge, N O; Afanas'ev, I B

1992-02-01

The mutagenic effect of chrysotile asbestos fibers and zeolite and latex particles on human lymphocytes in whole blood has been studied. It was concluded that their mutagenic activities were mediated by oxygen radicals because they were inhibited by antioxidant enzymes (SOD and catalase) and oxygen radical scavengers (rutin, ascorbic acid, and bemitil). It was proposed that oxygen radicals were released by phagocytes activated upon exposure to mineral dusts and fibers. The study of lucigenin- and luminol-amplified chemiluminescence of peritoneal macrophages stimulated by chrysotile fibers and zeolite and latex particles has shown that their mutagenic action is probably mediated by different oxygen species, namely, by the iron-oxygen complexes (perferryl ions) plus hydrogen peroxide, hydrogen peroxide, and superoxide ion, respectively. From the oxygen radical scavengers studied, rutin was the most effective inhibitor of the mutagenic effect of mineral fibers and dusts.

Overview of FIREMEN program at Ames Research Center

NASA Technical Reports Server (NTRS)

Kourtides, D. A.

1978-01-01

The Ames Firemen Program is described. The key elements of the program include: (1) the development and evaluation of aircraft interior composite panels; (2) the thermochemical and flammability characterization of thermoset and thermoplastic resins; and (3) the evolution of fire resist aircraft seat components. The first two elements are presented.

Evaluation of cytotoxicity, genotoxicity, and apoptosis of wastewater before and after disinfection with performic acid.

PubMed

Ragazzo, Patrizia; Feretti, Donatella; Monarca, Silvano; Dominici, Luca; Ceretti, Elisabetta; Viola, Gaia; Piccolo, Valentina; Chiucchini, Nicoletta; Villarini, Milena

2017-06-01

Disinfection with performic acid (PFA) represents an emerging technology in wastewater treatment. Many recent studies indicate its effectiveness and suitability as a disinfectant for different applications; several have demonstrated its reliability as an alternative to chlorine for disinfecting secondary effluents from urban wastewater treatment plants (WWTPs). Some disinfection technologies, in relation to their oxidative power, lead to the formation of disinfection by-products (DBPs), some of which are of concern for their toxic and carcinogenic potential. The aim of this study was to investigate potential genotoxic, cytotoxic, and mutagenic effects of this disinfection agent on treated secondary effluent coming from a municipal WWTP. A strategy with multiple short-term tests and different target cells (bacterial, plant, and mammalian) was adopted to explore a relatively wide range of potential genotoxic events. The Ames test (point mutation in Salmonella), the micronucleus (chromosomal damage) and Comet tests (primary DNA damage) on human hepatic cells (HepG2) were conducted to detect mutagenicity and chromosomal DNA alterations. DNA fragmentation and mitochondrial potential assays were conducted to evaluate apoptosis in the same kinds of cells. Mutagenic and clastogenic effect potentials were evaluated by examining micronucleus formation in Allium cepa root cells. In all the in vitro tests, carried out on both disinfected and non-disinfected effluents, negative results were always obtained for mutagenic and genotoxic effects. In the Allium cepa tests, however, some non-concentrated wastewater samples after PFA treatment induced a slight increase in micronucleus frequencies in root cells, but not in a dose-related manner. In conclusion, PFA applied for disinfection to a secondary effluent from a municipal wastewater treatment plant did not contribute to the release of genotoxic or mutagenic compounds. Further studies are required to establish to which extent

The 10th anniversary of the publication of genes and environment: memoir of establishing the Japanese environmental mutagen society and a proposal for a new collaborative study on mutagenic hormesis.

PubMed

Sutou, Shizuyo

2017-01-01

The Japanese Environmental Mutagen Society (JEMS) was established in 1972 by 147 members, 11 of whom are still on the active list as of May 1, 2016. As one of them, I introduce some historic topics here. These include 1) establishment of JEMS, 2) the issue of 2-(2-furyl)-3-(3-nitro-2-furyl)acrylamide (AF-2), 3) the Mammalian Mutagenicity Study Group (MMS) and its achievements, and 4) the Collaborative Study Group of the Micronucleus Test (CSGMT) and its achievements. In addition to these historic matters, some of which are still ongoing, a new collaborative study is proposed on adaptive response or hormesis by mutagens. There is a close relationship between mutagens and carcinogens, the dose-response relationship of which has been thought to follow the linear no-threshold model (LNT). LNT was fabricated on the basis of Drosophila sperm experiments using high dose radiation delivered in a short period. The fallacious 60 years-old LNT is applied to cancer induction by radiation without solid data and then to cancer induction by carcinogens also without solid data. Therefore, even the smallest amount of carcinogens is postulated to be carcinogenic without thresholds now. Radiation hormesis is observed in a large variety of living organisms; radiation is beneficial at low doses, but hazardous at high doses. There is a threshold at the boundary between benefit and hazard. Hormesis denies LNT. Not a few papers report existence of chemical hormesis. If mutagens and carcinogens show hormesis, the linear dose-response relationship in mutagenesis and carcinogenesis is denied and thresholds can be introduced.

Antimicrobial and Genotoxicity Effects of Zero-valent Iron Nanoparticles

PubMed Central

Barzan, Elham; Mehrabian, Sedigheh; Irian, Saeed

2014-01-01

Background: In a world of nanotechnology, the first concern is the potential environmental impact of nanoparticles. An efficient way to estimate nanotoxicity is to monitor the responses of bacteria exposed to these particles. Objectives: The current study explored the antimicrobial properties of nZVI (zero-valent Iron nanoparticles) on the Gram-negative bacterial systems Erwinia amylovora, Xanthomonas oryzae and the Gram-positive bacterial systems Bacillus cereus and Streptomyces spp. The genotoxicity potential of nZVI was also assayed. Materials and Methods: The toxicity of nZVI was tested by two different methods: Growing bacteria in liquid (broth dilution) and agar media (challenge test) containing different nZVI concentrations for 24-72 hours. The genotoxicity of nZVI was assessed using the preincubation version of the Ames test. Results: The lowest concentrations of nZVI that inhibited the visible growth (MIC) of E. amylovora, X. oryzae, B. cereus and Streptomyces spp. were 625, 550, 1250 and 1280 ppm, respectively. The minimum bactericidal concentration (MBC) for E. amylovora and X. oryzae were 10,000 and 5,000 ppm of nZVI, respectively. MBC was not observed for the Gram positive bacteria. No bacteriostatic and bactericidal effects were observed for oxidized nZVI. Mutant frequency did not increase according to the vehicle control at the concentrations assayed, indicating a lack of mutagenicity associated with nZVI. Conclusions: nZVI nanoparticles are not mutagenic at low concentrations, therefore they can be used without detrimental effects on soil bacteria. PMID:25147712

NASA Ames aerospace systems directorate research

NASA Technical Reports Server (NTRS)

Albers, James A.

1991-01-01

The Aerospace Systems Directorate is one of four research directorates at the NASA Ames Research Center. The Directorate conducts research and technology development for advanced aircraft and aircraft systems in intelligent computational systems and human-machine systems for aeronautics and space. The Directorate manages research and aircraft technology development projects, and operates and maintains major wind tunnels and flight simulation facilities. The Aerospace Systems Directorate's research and technology as it relates to NASA agency goals and specific strategic thrusts are discussed.

Semantic Web Infrastructure Supporting NextFrAMES Modeling Platform

NASA Astrophysics Data System (ADS)

Lakhankar, T.; Fekete, B. M.; Vörösmarty, C. J.

2008-12-01

Emerging modeling frameworks offer new ways to modelers to develop model applications by offering a wide range of software components to handle common modeling tasks such as managing space and time, distributing computational tasks in parallel processing environment, performing input/output and providing diagnostic facilities. NextFrAMES, the next generation updates to the Framework for Aquatic Modeling of the Earth System originally developed at University of New Hampshire and currently hosted at The City College of New York takes a step further by hiding most of these services from modeler behind a platform agnostic modeling platform that allows scientists to focus on the implementation of scientific concepts in the form of a new modeling markup language and through a minimalist application programming interface that provide means to implement model processes. At the core of the NextFrAMES modeling platform there is a run-time engine that interprets the modeling markup language loads the module plugins establishes the model I/O and executes the model defined by the modeling XML and the accompanying plugins. The current implementation of the run-time engine is designed for single processor or symmetric multi processing (SMP) systems but future implementation of the run-time engine optimized for different hardware architectures are anticipated. The modeling XML and the accompanying plugins define the model structure and the computational processes in a highly abstract manner, which is not only suitable for the run-time engine, but has the potential to integrate into semantic web infrastructure, where intelligent parsers can extract information about the model configurations such as input/output requirements applicable space and time scales and underlying modeling processes. The NextFrAMES run-time engine itself is also designed to tap into web enabled data services directly, therefore it can be incorporated into complex workflow to implement End-to-End application

A Survey of Knowledge Management Research & Development at NASA Ames Research Center

NASA Technical Reports Server (NTRS)

Keller, Richard M.; Clancy, Daniel (Technical Monitor)

2002-01-01

This chapter catalogs knowledge management research and development activities at NASA Ames Research Center as of April 2002. A general categorization scheme for knowledge management systems is first introduced. This categorization scheme divides knowledge management capabilities into five broad categories: knowledge capture, knowledge preservation, knowledge augmentation, knowledge dissemination, and knowledge infrastructure. Each of nearly 30 knowledge management systems developed at Ames is then classified according to this system. Finally, a capsule description of each system is presented along with information on deployment status, funding sources, contact information, and both published and internet-based references.

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

NASA Astrophysics Data System (ADS)

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.

Energy Remote Sensing Applications Projects at the NASA Ames Research Center

NASA Technical Reports Server (NTRS)

Norman, S. D.; Likens, W. C.; Mouat, D. A.

1982-01-01

The NASA Ames Research Center is active in energy projects primarily in the role of providing assistance to users in the solution of a number of problems related to energy. Data bases were produced which can be used, in combination with other sources of information, to solve spatially related energy problems. Six project activities at Ames are described which relate to energy and remote sensing. Two projects involve power demand forecasting and estimations using remote sensing and geographic information systems; two others involve transmission line routing and corridor analysis; one involves a synfuel user needs assessment through remote sensing; and the sixth involves the siting of energy facilities.

NASA Ames and Traveling Space Museum Host Space Day at Bay Area Schools (Version 2 - Final)

NASA Image and Video Library

2010-08-10

NASA Ames and the Traveling Space Museum visited under-represented students in the Bay Area in an effort to excite them to the possibilities in science, technology, engineering and mathematics. Includes soundbites from Lewis Braxton III (NASA Ames) and actress Nichelle Nichols (TSM).

Genotoxicity studies on DNA-interactive telomerase inhibitors with application as anti-cancer agents.

PubMed

Harrington, Dean J; Cemeli, Eduardo; Carder, Joanna; Fearnley, Jamie; Estdale, Sian; Perry, Philip J; Jenkins, Terence C; Anderson, Diana

2003-01-01

Telomerase-targeted strategies have aroused recent interest in anti-cancer chemotherapy, because DNA-binding drugs can interact with high-order tetraplex rather than double-stranded (duplex) DNA targets in tumour cells. However, the protracted cell-drug exposure times necessary for clinical application require that telomerase inhibitory efficacy must be accompanied by both low inherent cytotoxicity and the absence of mutagenicity/genotoxicity. For the first time, the genotoxicity of a number of structurally diverse DNA-interactive telomerase inhibitors is examined in the Ames test using six Salmonella typhimurium bacterial strains (TA1535, TA1537, TA1538, TA98, TA100, and TA102). DNA damage induced by each agent was also assessed using the Comet assay with human lymphocytes. The two assay procedures revealed markedly different genotoxicity profiles that are likely to reflect differences in metabolism and/or DNA repair between bacterial and mammalian cells. The mutational spectrum for a biologically active fluorenone derivative, shown to be mutagenic in the TA100 strain, was characterised using a novel and rapid assay method based upon PCR amplification of a fragment of the hisG46 allele, followed by RFLP analysis. Preliminary analysis indicates that the majority (84%) of mutations induced by this compound are C --> A transversions at position 2 of the missense proline codon of the hisG46 allele. However, despite its genotoxic bacterial profile, this fluorenone agent gave a negative response in the Comet assay, and demonstrates how unwanted systemic effects (e.g., cytotoxicity and genotoxicity) can be prevented or ameliorated through suitable molecular fine-tuning of a candidate drug in targeted human tumour cells. Copyright 2003 Wiley-Liss, Inc.

Long-range transport of mutagens and other air pollutants from mainland East Asia to western Japan.

PubMed

Coulibaly, Souleymane; Minami, Hiroki; Abe, Maho; Hasei, Tomohiro; Oro, Tadashi; Funasaka, Kunihiro; Asakawa, Daichi; Watanabe, Masanari; Honda, Naoko; Wakabayashi, Keiji; Watanabe, Tetsushi

2015-01-01

Asian dust events, transport of dust particles from arid and semi-arid areas in China and Mongolia to the east by prevailing westerlies, are often observed in Japan in spring. In recent decades, consumption of fossil fuels has markedly increased in mainland East Asia with rapid economic growth, and severe air pollution has occurred. A part of air pollutants including mutagens, such as polycyclic aromatic hydrocarbons (PAHs), generated in mainland East Asia are thought to be transported to Japan by the prevailing westerlies, like Asian dust, and winter monsoon. The objective of this study was to clarify the long-range transport of mutagens and other air pollutants in East Asia. Thus, we collected total suspended particles (TSP) at a rural town in western Japan, namely, Yurihama in Tottori Prefecture, for 1 year (June 2012-May 2013), and investigated their chemical constituents and mutagenicity. Many TSP collected from January to March showed high mutagenicity toward Salmonella typhimurium YG1024 with and without S9 mix, and high levels of lead (Pb) and sulfate ions (SO4 (2-)), which are indicators of transboundary air pollutions from mainland East Asia, were detected in those TSP. A large amount of iron, which is an indicator of sand, was found in highly mutagenic TSP collected in March, but not in TSP collected in January and February. High levels of PAHs were detected in highly mutagenic TSP collected from January to March. The ratios of the concentration of fluoranthene to those of fluoranthene and pyrene suggested that the main source of PAHs in TSP collected in winter and spring was coal and biomass combustion. Backward trajectories of air masses on days when high levels of mutagenicity were found indicated that these air masses had traveled from eastern or northern China to Yurihama. These results suggest that high levels of mutagens were transported from mainland East Asia to western Japan, and this transportation accompanied Asian dust in March, but not in

Urinary mutagenicity and N-acetylation phenotype in textile industry workers exposed to arylamines

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

Sinues, B.; Perez, J.; Bernal, M.L.

1992-09-15

Primary aromatic amines have been identified epidemiologically as human carcinogens. It has been suggested that the target organ affected by aromatic amines is dependent on the rate of metabolic activation. Epidemiological studies have shown an association between low acetyl transferase activity and bladder cancer risk. On this basis, our working hypothesis was that the slow acetylators could follow in a higher extent the metabolic pathway independent of N-acetylation, leading to the excretion of conjugates of electrophyles with glucuronic acid. The instability of these glucuronides could be responsible for the association between arylamine-induced bladder cancer and slow acetylator phenotype. A totalmore » of 153 individuals were included in this study: 70 exposed to arylamines (working in textile industry) and 83 nonexposed. The following parameters were determined in urine: mutagenic index in the absence of metabolic activation, S9; mutagenic index in the presence of S9; and the mutagenic index after incubation of the urine with beta-glucuronidase. All individuals were phenotyped according to their capacity of N-acetylation by using isoniazid as drug test. The results show that the mutagenic index after incubation of the urine with beta-glucuronidase is statistically higher in exposed subjects when compared with nonexposed individuals (P less than 0.001), this parameter being statistically higher among exposed subjects who were slow acetylators than among rapid metabolizers, independent of the fact that they were smokers or nonsmokers. There were no significant differences between groups for the mutagenicity in urine not incubated with beta-glucuronidase.« less

Mutagenic effect of accelerated heavy ions on bacterial cells

NASA Astrophysics Data System (ADS)

Boreyko, A. V.; Krasavin, E. A.

2011-11-01

features of energy transfer of the radiations that affect the character of induced DNA damage, and the efficiency inducible and constitutive cell repair systems. The growth of relative biological efficiency of heavy charged particles is determined by the growth of the damage yield of the DNA participating in the formation of radiation-induced effects, and higher efficiency of inducible repair systems. It was established that the LET value ( L max) for which the maximum (according to the applied irradiation criteria) coefficients of relative biological efficiency are observed varies depending on the character of the registered radiation induced effect. It was demonstrated that for gene mutations and induction of precision excision of mobile elements the values of L max are realized in a LET range of ≈20 keV/μm. For lethal effects of irradiation and induction of deletion mutations the value of L max is ≈ 100 and 50 keV/μm, respectively. The differences in the L max for the studied radiation gene effectis are determined by the different type of DNA damage participating in the mutation process. A molecular model of the formation of gene mutations in Escherichia coli cells under the action of ionizing radiation was proposed. Basic DNA radiation damage and main repair ways were considered in the framework of this model. The basis is the idea of the decisive role of mutagenic, error-prone, branch of SOS repair in fixing premutation DNA damage into point mutations. It was demonstrated that the central mechanism in this process is the formation of an inducible multi-enzymatic complex including the DNA polymerase V (Umu C), RecA-protease, SSB proteins, subunits of DNA polymerase III, performing erroneous DNA synthesis on the damaged matrix. A mathematical model of induction of gene mutations under ultraviolet cell irradiation was developed based on the molecular model.

Developing questionnaires for educational research: AMEE Guide No. 87

PubMed Central

La Rochelle, Jeffrey S.; Dezee, Kent J.; Gehlbach, Hunter

2014-01-01

In this AMEE Guide, we consider the design and development of self-administered surveys, commonly called questionnaires. Questionnaires are widely employed in medical education research. Unfortunately, the processes used to develop such questionnaires vary in quality and lack consistent, rigorous standards. Consequently, the quality of the questionnaires used in medical education research is highly variable. To address this problem, this AMEE Guide presents a systematic, seven-step process for designing high-quality questionnaires, with particular emphasis on developing survey scales. These seven steps do not address all aspects of survey design, nor do they represent the only way to develop a high-quality questionnaire. Instead, these steps synthesize multiple survey design techniques and organize them into a cohesive process for questionnaire developers of all levels. Addressing each of these steps systematically will improve the probabilities that survey designers will accurately measure what they intend to measure. PMID:24661014

Developing questionnaires for educational research: AMEE Guide No. 87.

PubMed

Artino, Anthony R; La Rochelle, Jeffrey S; Dezee, Kent J; Gehlbach, Hunter

2014-06-01

In this AMEE Guide, we consider the design and development of self-administered surveys, commonly called questionnaires. Questionnaires are widely employed in medical education research. Unfortunately, the processes used to develop such questionnaires vary in quality and lack consistent, rigorous standards. Consequently, the quality of the questionnaires used in medical education research is highly variable. To address this problem, this AMEE Guide presents a systematic, seven-step process for designing high-quality questionnaires, with particular emphasis on developing survey scales. These seven steps do not address all aspects of survey design, nor do they represent the only way to develop a high-quality questionnaire. Instead, these steps synthesize multiple survey design techniques and organize them into a cohesive process for questionnaire developers of all levels. Addressing each of these steps systematically will improve the probabilities that survey designers will accurately measure what they intend to measure.

Unique life sciences research facilities at NASA Ames Research Center

NASA Technical Reports Server (NTRS)

Mulenburg, G. M.; Vasques, M.; Caldwell, W. F.; Tucker, J.

1994-01-01

The Life Science Division at NASA's Ames Research Center has a suite of specialized facilities that enable scientists to study the effects of gravity on living systems. This paper describes some of these facilities and their use in research. Seven centrifuges, each with its own unique abilities, allow testing of a variety of parameters on test subjects ranging from single cells through hardware to humans. The Vestibular Research Facility allows the study of both centrifugation and linear acceleration on animals and humans. The Biocomputation Center uses computers for 3D reconstruction of physiological systems, and interactive research tools for virtual reality modeling. Psycophysiological, cardiovascular, exercise physiology, and biomechanical studies are conducted in the 12 bed Human Research Facility and samples are analyzed in the certified Central Clinical Laboratory and other laboratories at Ames. Human bedrest, water immersion and lower body negative pressure equipment are also available to study physiological changes associated with weightlessness. These and other weightlessness models are used in specialized laboratories for the study of basic physiological mechanisms, metabolism and cell biology. Visual-motor performance, perception, and adaptation are studied using ground-based models as well as short term weightlessness experiments (parabolic flights). The unique combination of Life Science research facilities, laboratories, and equipment at Ames Research Center are described in detail in relation to their research contributions.

The enhancing effect of ethanol on the mutagenic activation of N-nitrosomethylbenzylamine by cytochrome P450 2A in the rat oesophagus.

PubMed

Tatematsu, Kenjiro; Koide, Akihiro; Morimura, Keiichirou; Fukushima, Shoji; Mori, Yukio

2013-03-01

Alcohol consumption is frequently associated with various cancers and the enhancement of the metabolic activation of carcinogens has been proposed as a mechanism underlying this relationship. The ethanol-induced enhancement of N-nitrosodiethylamine (DEN)-mediated carcinogenesis can be attributed to an increase in hepatic activity. However, the mechanism of elevation of N-nitrosomethylbenzylamine (NMBA)-induced tumorigenesis remains unclear. To elucidate the mechanism underlying the role of ethanol in the enhancement of NMBA-induced oesophageal carcinogenesis, we evaluated the hepatic and extrahepatic levels of the cytochrome P450 (CYP) and mutagenic activation of environmental carcinogens by immunoblot analyses and Ames preincubation test, respectively, in F344 rats treated with ethanol. Five weeks of treatment with 10% ethanol added to the drinking water or two intragastric treatments with 50% ethanol, both resulted in elevated levels of CYP2E1 (1.5- to 2.3-fold) and mutagenic activities of DEN, N-nitrosodimethylamine and N-nitrosopyrrolidine in the presence of rat liver S9 (1.5- to 2.4-fold). This was not the case with CYP1A1/2, CYP2A1/2, CYP2B1/2 or CYP3A2, nor with the activities of 2-amino-3-methylimidazo[4,5-f]quinoline, 3-amino-1-methyl-5H-pyrido[4,3-b]indole, aflatoxin B(1) or other N-nitroso compounds (NOCs), including NMBA. Ethanol-induced elevations of CYP2A and CYP2E1 were observed in the oesophagus (up to 1.7- and 2.3-fold) and kidney (up to 1.5- and 1.8-fold), but not in the lung or colon. In oesophagus and kidney, the mutagenic activities of NMBA and four NOCs were markedly increased (1.3- to 2.4-fold) in treated rats. The application of several CYP inhibitors revealed that CYP2A were likely to contribute to the enhancing effect of ethanol on NMBA activation in the rat oesophagus and kidney, but that CYP2E1 failed to do so. These results showed that the enhancing effect of ethanol on NMBA-induced oesophageal carcinogenesis could be attributed to an

Declaring the Existence of Human Germ-Cell Mutagens

EPA Science Inventory

After more than 80 years of searching for human germ-cell mutagens, I think that sufficient evidence already exists for a number of agents to be so considered, and definitive confirmation seems imminent due to the application ofrecently developed genomic techniques. In preparatio...

Visualization of fluid dynamics at NASA Ames

NASA Technical Reports Server (NTRS)

Watson, Val

1989-01-01

The hardware and software currently used for visualization of fluid dynamics at NASA Ames is described. The software includes programs to create scenes (for example particle traces representing the flow over an aircraft), programs to interactively view the scenes, and programs to control the creation of video tapes and 16mm movies. The hardware includes high performance graphics workstations, a high speed network, digital video equipment, and film recorders.

17. Woodworking Mill (basement): view looking north showing Ames Iron ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

17. Woodworking Mill (basement): view looking north showing Ames Iron Works steam boiler; note turbine control handle in middle right of photo - Ben Thresher's Mill, State Aid No. 1, Barnet, Caledonia County, VT

Peregrine Rocket Motor Test at the Ames Outdoor Aerodynamic Rese

NASA Image and Video Library

2017-02-15

(Left): Kyle Botteon (front) and Hunjpp Kim (Behind), NASA JPL. (Right): Gregory Zilliac, Advance Propulsion Technician. NASA Ames, preparing the Peregrine Hybrid Rocket Engine at the Outdoor Aerodynamic Research Facility (OARF, N-249).

Practical aspects of mutagenicity testing strategy: an industrial perspective.

PubMed

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.

Evaluation of antioxidant and mutagenic activities of honey-sweetened cashew apple nectar.

PubMed

da Silva, Robson Alves; Dihl, Rafael Rodrigues; Nascimento e Santos, Débora; de Abreu, Bianca Regina Ribas; de Lima, Alessandro; de Andrade, Heloisa Helena Rodrigues; Lehmann, Mauricio

2013-12-01

In vitro chemical properties and antioxidant potential and in vivo mutagenic activity of honey-sweetened cashew apple nectar (HSCAN), a beverage produced from the cashew pseudo-fruit (Anacardium occidentale L.) and of its constituents were assessed. Analytical procedures were carried out to investigate the honey used in the HSCAN preparation, and the results observed are in accordance with Brazilian legal regulations, except for diastase number. HSCAN and pulp were investigated for ascorbic acid, carotenoid, anthocyanin and total phenolic contents, and both showed high acid ascorbic concentrations. Antioxidant capacity using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and/or β-carotene/linoleic acid systems were applied and demonstrated a weak antioxidant capacity of honey and HSCAN, but cashew apple pulp demonstrated high antioxidant capacity. A weakly positive mutagenic effect of cashew pulp 20% was observed using the somatic mutation and recombination test (SMART) in Drosophila melanogaster only in the high-bioactivation (HB) cross. On the contrary, HSCAN was not mutagenic in both standard and high bioactivation crosses. HSCAN exhibited slight antioxidant activity, which could be associated with the high amount of ascorbic acid found in the samples evaluated. The beverage prepared did not induce DNA damage in somatic cells of D. melanogaster, which means that it is neither mutagenic nor recombinagenic in this test system. Copyright © 2013 Elsevier Ltd. All rights reserved.

The microRNA ame-miR-279a regulates sucrose responsiveness of forager honey bees (Apis mellifera).

PubMed

Liu, Fang; Shi, Tengfei; Yin, Wei; Su, Xin; Qi, Lei; Huang, Zachary Y; Zhang, Shaowu; Yu, Linsheng

2017-11-01

Increasing evidence demonstrates that microRNAs (miRNA) play an important role in the regulation of animal behaviours. Honey bees (Apis mellifera) are eusocial insects, with honey bee workers displaying age-dependent behavioural maturation. Many different miRNAs have been implicated in the change of behaviours in honey bees and ame-miR-279a was previously shown to be more highly expressed in nurse bee heads than in those of foragers. However, it was not clear whether this difference in expression was associated with age or task performance. Here we show that ame-miR-279a shows significantly higher expression in the brains of nurse bees relative to forager bees regardless of their ages, and that ame-miR-279a is primarily localized in the Kenyon cells of the mushroom body in both foragers and nurses. Overexpression of ame-miR-279a attenuates the sucrose responsiveness of foragers, while its absence enhances their sucrose responsiveness. Lastly, we determined that ame-miR-279a directly target the mRNA of Mblk-1. These findings suggest that ame-miR-279a plays important roles in regulating honey bee division of labour. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antimutagenic and anticarcinogenic effects of betel leaf extract against the tobacco-specific nitrosamine 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK).

PubMed

Bhide, S V; Padma, P R; Amonkar, A J

1991-01-01

Earlier studies showed that betel leaf inhibits the mutagenic action of standard mutagens like benzo[a]pyrene and dimethylbenz[a]anthracene. Since tobacco-specific nitrosamines are the major carcinogens present in unburnt forms of tobacco, we studied the effect of an extract of betel leaf on the mutagenic and carcinogenic actions of one of the most potent, 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK). Betel-leaf extract and hydroxychavicol suppressed the mutagenicity of NNK in both the Ames and the micronucleus test. In studies in mice, betel-leaf extract reduced the tumorigenic effects of NNK by 25%. Concurrent treatment with the extract also inhibited the decreases in levels of vitamin A in liver and plasma induced by NNK. Betel leaf thus has protective effects against the mutagenic, carcinogenic and adverse metabolic effects of NNK in mice.

Mutagenicity and Pollutant Emission Factors of Solid-Fuel Cookstoves: Comparison with Other Combustion Sources

PubMed Central

Mutlu, Esra; Warren, Sarah H.; Ebersviller, Seth M.; Kooter, Ingeborg M.; Schmid, Judith E.; Dye, Janice A.; Linak, William P.; Gilmour, M. Ian; Jetter, James J.; Higuchi, Mark; DeMarini, David M.

2016-01-01

Background: 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. Objective: We evaluated two categories of solid-fuel cookstoves for eight pollutant and four mutagenicity emission factors, correlated the mutagenicity emission factors, and compared them to those of other combustion emissions. Methods: We burned red oak in a 3-stone fire (TSF), a natural-draft stove (NDS), and a forced-draft stove (FDS), and 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. Results: With the exception of NOx, the emission factors per MJd were highly correlated (r ≥ 0.97); the correlation for NOx with the other emission factors was 0.58–0.76. Excluding NOx, the NDS and FDS reduced the emission factors an average of 68 and 92%, respectively, relative to the TSF. Nevertheless, the mutagenicity emission factor based on fuel energy used (MJthermal) for the most efficient stove (FDS) was between those of a large diesel bus engine and a small diesel generator. Conclusions: Both mutagenicity and pollutant emission factors may be informative for characterizing cookstove performance. However, mutagenicity emission factors may be especially useful for characterizing potential health effects and should be evaluated in relation to health outcomes in future research. An FDS operated as intended by the manufacturer is safer than a TSF, but without adequate ventilation, it will still result in poor indoor air quality. Citation: Mutlu E, Warren SH, Ebersviller SM, Kooter IM, Schmid JE, Dye JA, Linak WP, Gilmour MI, Jetter

Ames Hybrid Combustion Facility

NASA Technical Reports Server (NTRS)

Zilliac, Greg; Karabeyoglu, Mustafa A.; Cantwell, Brian; Hunt, Rusty; DeZilwa, Shane; Shoffstall, Mike; Soderman, Paul T.; Bencze, Daniel P. (Technical Monitor)

2003-01-01

The report summarizes the design, fabrication, safety features, environmental impact, and operation of the Ames Hybrid-Fuel Combustion Facility (HCF). The facility is used in conducting research into the scalability and combustion processes of advanced paraffin-based hybrid fuels for the purpose of assessing their applicability to practical rocket systems. The facility was designed to deliver gaseous oxygen at rates between 0.5 and 16.0 kg/sec to a combustion chamber operating at pressures ranging from 300 to 900. The required run times were of the order of 10 to 20 sec. The facility proved to be robust and reliable and has been used to generate a database of regression-rate measurements of paraffin at oxygen mass flux levels comparable to those of moderate-sized hybrid rocket motors.

The Impact on DoD of the Toxic Substances Control Act

DTIC Science & Technology

1980-06-01

reconcile a limit of 10 ppm in the gasoline area where there is a potential for 400,000 exposures while in the rubber industry the potential is only 150,000...that the Ames test and other mutagenic tests are predictive of tumor producing potential. Many of us in toxi - cology are not impressed with this...also be completely different; so much for generic toxi - cology and for the possibility that short term testing for mutagenic effects is predictive of

(New) NASA Administrator Sean O'Keefe comes to Ames for employee briefing and tour. Here he welcomes

NASA Technical Reports Server (NTRS)

2002-01-01

(New) NASA Administrator Sean O'Keefe comes to Ames for employee briefing and tour. Here he welcomes JASON kids to NASA while handing out patches and pins. Tom Clausen and Donald James, Ames Education Office in background.

Mutagenicity testing of the antiparasitic drug entizol (polfa) in the detection system of Salmonella typhimurium mutants.

PubMed

Dobiás, L

1980-02-01

The mutagenic activity was tested of a clinically used drug Entizol (Polfa) which contains metronidazole as an active substance. The mutagenicity of the compound was detected for Salmonella typhimurium indicator strains TA100, TA1535, TA1950, and TA1538 in tests in vitro without metabolic activation at the concentration range of 180 to 1600 microgram per plate. Metabolic conversion of the preparation studied in vivo gave rise to mutagenic metabolites detectable in the blood of mice after both intraperitoneal and per-oral application. The presence of the products of drug metabolism in the blood of experimental animals was tested at 1-40 h intervals after application. Blood samples of mice treated intraperitoneally with single doses of 1470 and 35 mg/kg were tested in strains TA100 and TA98. There were differences in the times of occurrence of mutagenic metabolites. The development of two mutagenicity maxima, detected in the blood withdrawn within the interval of 60-120 min (Rt/Rc 3.1) and 19 h (Rt/Rc 24.8) after the application of a dose of 1470 mg/kg in the strain TA100, is characteristic. The mutagenic effect of the blood of animals treated with a dose of 35 mg/kg, which approximately corresponds to standard therapeutic values, also had an analogous character. The highest mutagenic effect was detected in blood samples withdrawn 19 h after application (Rt/Rc 15.8). The frameshift mutation-detecting strain TA98 reverted at a lower frequency (about 5 times) under the above conditions, but only during analysis of the blood samples of animals treated with a dose of 1470 mg/kg. These results indicate that, for assessing the mutagenicity of 5-nitroimidazole compounds and their metabolites in blood, it is necessary to analyse blood samples withdrawn at least up to 24 h after application of the compound. This relationship was not proved to exist between the frequencies of induced revertants during the testing of blood withdrawn within 1-24 h after single per

RESIDUAL MUTAGENICITY OF THE ALASKAN OIL SPILL ORGANICS

EPA Science Inventory

RESIDUAL MUTAGENICITY OF THE ALASKAN OIL SPILL ORGANICS. L.D.

The Exxon Valdez, on March 24, 1989, spilled approximately eleven million gallons of Prudhoe Bay crude oil into the waters of Prince William Sound. Approximately 300 miles of
contaminated beach are potential...

Comparison of Heat Flux Gages for High Enthalpy Flows - NASA Ames and IRS

NASA Technical Reports Server (NTRS)

Loehle, Stefan; Nawaz, Anuscheh; Herdrich, Georg; Fasoulas, Stefanos; Martinez, Edward; Raiche, George

2016-01-01

This article is a companion to a paper on heat flux measurements as initiated under a Space Act Agreement in 2011. The current focus of this collaboration between the Institute of Space Systems (IRS) of the University of Stuttgart and NASA Ames Research Center is the comparison and refinement of diagnostic measurements. A first experimental campaign to test different heat flux gages in the NASA Interaction Heating Facility (IHF) and the Plasmawindkanaele (PWK) at IRS was established. This paper focuses on the results of the measurements conducted at IRS. The tested gages included a at face and hemispherical probe head, a 4" hemispherical slug calorimeter, a null-point calorimeter from Ames and a null-point calorimeter developed for this purpose at IRS. The Ames null-point calorimeter was unfortunately defective upon arrival. The measured heat fluxes agree fairly well with each other. The reason for discrepancies can be attributed to signal-to-noise levels and the probe geometry.

Mutagenic effect of freezing on nuclear DNA of Saccharomyces cerevisiae.

PubMed

Todorova, T; Pesheva, M; Stamenova, R; Dimitrov, M; Venkov, P

2012-05-01

Although fragmentation of DNA has been observed in cells undergoing freezing procedures, a mutagenic effect of sub-zero temperature treatment has not been proved by induction and isolation of mutants in nuclear DNA (nDNA). In this communication we supply evidence for mutagenicity of freezing on nDNA of Saccharomyces cerevisiae cells. In the absence of cryoprotectors, cooling for 2 h at +4°C and freezing for 1 h at -10°C and 16 h at -20°C, with a cooling rate of 3°C/min, resulted in induction of frame-shift and reverse mutations in microsatellite and coding regions of nDNA. The sub-zero temperature exposure also has a strong recombinogenic effect, evidenced by induction of gene-conversion and crossing-over events. Freezing induces mutations and enhances recombination with a frequency equal to or higher than that of methylmethanesulphonate at comparable survival rates. The signals for the appearance of nDNA lesions induced by freezing are detected and transduced by the DNA damage pathway. Extracellular cryoprotectors did not prevent the mutagenic effect of freezing, while accumulation of trehalose inside cells reduced nDNA cryodamage. Freezing of cells is accompanied by generation of high ROS levels, and the oxidative stress raised during the freeze-thaw process is the most likely reason for the DNA damaging effect. Experiments with mitochondrial rho⁻ mutants or scavengers of ROS indicated that mutagenic and recombinogenic effects of sub-zero temperatures can be decreased but not eliminated by reduction of ROS level. The complete protection against cryodamage in nDNA required simultaneous usage of intracellular cryoprotector and ROS scavenger during the freeze-thaw process. Copyright © 2012 John Wiley & Sons, Ltd.

Toxicity, uptake, and mutagenicity of particulate and soluble nickel compounds.

PubMed Central

Fletcher, G G; Rossetto, F E; Turnbull, J D; Nieboer, E

1994-01-01

Toxicity testing in AS52 cells (24-hr exposures) gave LC50 values of 2 to 130 micrograms Ni/ml for particulate nickel compounds and 45 to 60 micrograms Ni/ml for water-soluble salts (NiCl2, NiSO4, Ni(CH3COO)2). The Ni(OH)2, NiCO3, and sulfides (Ni3S2, Ni7S6, "amorphous NiS") exhibited similar toxicities (LC50's of 2 to 8 micrograms Ni/ml), while three nickel oxides were more variable and less toxic (LC50's of 18 to 130 micrograms Ni/ml). Most compounds displayed nuclear to cytoplasmic nickel ratios of approximately 1:1.5 to 1:5 (except approximately 1:20 for nickel salts). At the LC50's, a 75-fold range in exposure levels occurred compared to a 10-fold range in cytoplasmic and nuclear nickel concentrations, [Ni]. Cellular nickel distribution indicated three groupings: inert compounds (green NiO, lithium nickel oxide, relatively low nuclear and cytosolic [Ni]); water-soluble salts (very low nuclear [Ni]; high cytosolic [Ni]), and slightly soluble compounds (relatively high cytosolic and nuclear [Ni]). Nickel compounds are considered to be only weak or equivocal mutagens. In this study, a low but significant increase in mutation rate at the gpt locus was shown. Although the results would not be sufficient to deem nickel compounds mutagenic by traditional criteria, characterization by PCR analysis indicated that the spontaneous and nickel-induced mutants exhibited different and compound-specific mutational spectra (thus confirming nickel compound involvement). The results reported illustrate some of the methodologic problems involved in testing "weak" mutagens and indicate that alternative approaches may be necessary in classifying the mutagenicity of nickel and other compounds. PMID:7843140

Study of optical techniques for the Ames unitary wind tunnel, part 7

NASA Technical Reports Server (NTRS)

Lee, George

1993-01-01

A summary of optical techniques for the Ames Unitary Plan wind tunnels are discussed. Six optical techniques were studied: Schlieren, light sheet and laser vapor screen, angle of attack, model deformation, infrared imagery, and digital image processing. The study includes surveys and reviews of wind tunnel optical techniques, some conceptual designs, and recommendations for use of optical methods in the Ames Unitary Plan wind tunnels. Particular emphasis was placed on searching for systems developed for wind tunnel use and on commercial systems which could be readily adapted for wind tunnels. This final report is to summarize the major results and recommendations.

Studies on the contributions of smoke constituents, individually and in mixtures, in a range of in vitro bioactivity assays.

PubMed

Stabbert, Regina; Dempsey, Ruth; Diekmann, Joerg; Euchenhofer, Christian; Hagemeister, Timo; Haussmann, Hans-Juergen; Knorr, Arno; Mueller, Boris P; Pospisil, Pavel; Reininghaus, Wolf; Roemer, Ewald; Tewes, Franz J; Veltel, Detlef J

2017-08-01

Tobacco smoke is a complex mixture with over 8700 identified constituents. Smoking causes many diseases including lung cancer, cardiovascular disease, and chronic obstructive pulmonary disease. However, the mechanisms of how cigarette smoke impacts disease initiation or progression are not well understood and individual smoke constituents causing these effects are not generally agreed upon. The studies reported here were part of a series of investigations into the contributions of selected smoke constituents to the biological activity of cigarette smoke. In vitro cytotoxicity measured by the neutral red uptake (NRU) assay and in vitro mutagenicity determined in the Ames bacterial mutagenicity assay (BMA) were selected because these assays are known to produce reproducible, quantitative results for cigarette smoke under standardized exposure conditions. In order to determine the contribution of individual cigarette smoke constituents, a fingerprinting method was developed to semi-quantify the mainstream smoke yields. For cytotoxicity, 90% of gas vapor phase (GVP) cytotoxicity of the Kentucky Reference cigarette 1R4F was explained by 3 aldehydes and 40% of the 1R4F particulate phase cytotoxicity by 10 smoke constituents, e.g., hydroquinone. In the microsuspension version of the BMA, 4 aldehydes accounted for approximately 70% of the GVP mutagenicity. Finally, the benefits of performing such studies along with the difficulties in interpretation in the context of smoking are discussed. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Carcinogenicity and mutagenicity of chromium.

PubMed

Léonard, A; Lauwerys, R R

1980-11-01

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

Systematic and comprehensive investigation of the toxicity of curcuminoid‑essential oil complex: A bioavailable turmeric formulation.

PubMed

Aggarwal, Madan L; Chacko, Karampendethu M; Kuruvilla, Binu T

2016-01-01

Curcumin, the active component present in Curcuma longa of the family Zingiberaceae, has a number of pharmacological effects, including potential anti‑inflammatory activity. One of the major limitations of curcumin/turmeric extract is its poor absorption through the gastrointestinal tract. Several approaches have been adopted to increase the bioavailability of curcumin, including loading curcumin into liposomes or nanoparticles, complexation with phospholipids, addition of essential oils and synthesizing structural analogues of curcumin. In the present study, the toxicity and safety of one such bioavailable turmeric formulation, curcuminoid‑essential oil complex (CEC), the toxicity profile of which has not been reported, were examined using in vivo and in vitro models, as per the guidelines of the Organisation for Economic Co-operation and Development. Investigations of acute toxicity study were performed in rats and mice, and the results revealed no signs and symptoms or toxicity or mortality in any of the animals at the maximum recommended dose level of 5,000 mg/kg body weight. The repeated administration of CEC for 90 days in Wistar rats at a dose of 1,000 mg/kg body weight did not induce any observable toxic effects, compared with corresponding control animals. Mutagenicity/genotoxicity investigations were also performed using a bacterial reverse mutation assay (Ames test), a mammalian bone marrow chromosome aberration test and a mammalian erythrocyte micronucleus test in mice. CEC was found to be non‑mutagenic in all three mutagenic investigations. Consequently, the present study indicated that CEC elicited no toxic effects in animals or in vitro. Therefore, following investigations of acute toxicity, repeated dose toxicity and mutagenicity, CEC was deemed a safe, non‑toxic pharmacological formulation.

Mutagenic, cytotoxic, and teratogenic effects of 2-acetylaminofluorene and reactive metabolites in vitro.

PubMed

Faustman-Watts, E M; Yang, H Y; Namkung, M J; Greenaway, J C; Fantel, A G; Juchau, M R

1984-01-01

The embryotoxic, mutagenic, and cytotoxic properties of 2-acetylaminofluorene (AAF) and two of its reactive metabolites, N-acetoxy-2-acetylaminofluorene (AAAF) and 2-nitrosofluorene (NF) were assessed in vitro. A combined embryo culture/biotransformation system was used to determine the ability of these compounds to produce embryonic malformations, growth retardation, and/or embryolethality. Salmonella typhimurium auxotrophs (his-) were utilized to measure the mutagenic and cytotoxic potentials of these compounds. The parent compound, AAF, did not produce embryonic malformations or mutagenicity in the absence of an added cytochrome P-450-dependent monooxygenase system. Both metabolites produced each of the measured toxic effects without supplementation of a bioactivation system. However, the three chemicals each elicited a different spectrum of malformations. Bioactivated AAF produced neural tube abnormalities, whereas embryos treated with AAAF primarily exhibited prosencephalic malformations, and NF produced abnormalities of axial rotation or flexure. NF was approximately ten times more potent than AAAF as a direct-acting mutagen but only slightly more active in producing embryonic malformations in vitro. The results indicated that differential effects on the various measured parameters could be produced by these chemicals. The results indicated further that neither NF nor AAAF appeared to be individually responsible for the neural tube abnormalities generated by biotransformed AAF.

Peregrine Rocket Motor Test at the Ames Outdoor Aerodynamic Rese

NASA Image and Video Library

2017-02-15

Ashley Karp, NASA JPL (Left) and Hunjoo Kim, NASA JPL (Right) attaching heat sensors the Peregrine Hybrid Rocket Engine prior to its test at the Outdoor Aerodynamic Research Facility (OARF, N-249) at NASA's Ames Research Center.

Excretion of 3-hydroxy-benzo(a)pyrene and mutagenicity in rat urine after exposure to benzo(a)pyrene.

PubMed

Jongeneelen, F J; Leijdekkers, C M; Bos, R P; Theuws, J L; Henderson, P T

1985-10-01

3-hydroxy-benzo(a)pyrene (3-OH-B(a)P) and mutagenic activity in rat urine were determined after the oral administration of benzo(a)pyrene given in three repeated doses of 10, 20 and 50 mumol kg-1. The procedure for the determination of 3-OH-B(a)P consisted of enzymic hydrolysis, separation and HPLC-analysis. The mutagenic activity of concentrated urine samples was assayed with the Salmonella typhimurium strain TA98 in the presence of S9 mix and beta-glucuronidase. The urinary excretion of 3-OH-B(a)P and mutagens showed a correlation and both increased dose-dependently during the sampling period of 6 days. Data indicated that 3-OH-B(a)P can be regarded as a reliable representative of all urinary (pre)-mutagens derived from benzo(a)pyrene and exposure of rats to benzo(a)pyrene could be detected with greater sensitivity by the HPLC assay of 3-OH-B(a)P than with the non-specific mutagenicity assay.

Antimutagenic properties of Mangifera indica L. stem bark extract and evaluation of its effects on hepatic CYP1A1.

PubMed

Morffi, Janet; Rodeiro, Idania; Hernández, Sandra Luz; González, Leonora; Herrera, Jose; Espinosa-Aguirre, J Javier

2012-09-01

Mangifera indica stem bark extract (MSBE) is a Cuban natural product which has shown strong antioxidant properties. In this work, the antimutagenic effect of MSBE was tested against 10 well-known mutagens/carcinogens in the Ames test in the absence or presence of metabolic fraction (S9). The chemical mutagens tested included: cyclophosphamide, mitomycin C, bleomycin, cisplatin, dimethylnitrosamine (DMNA), benzo[a]pyrene (BP), 2-acetylaminofluorene (2-AAF), sodium azide, 1-nitropyrene (1-NP) and picrolonic acid. Protective effects of the extract were also evaluated by comparing the efficiency of S9 fraction obtained from rats treated during 28 days with oral doses of MSBE (50-500 mg/kg) with that obtained from rats treated with vehicle (control) to activate bleomycin and cyclophosphamide in the Ames test. MSBE concentrations between 50 and 500 μg/plate significantly reduced the mutagenicity mediated by all the chemicals tested with the exception of sodium azide. Higher mutagenicity was found when bleomycin and cyclophosphamide (CP) were activated by control S9 than by MSBE S9. In addition, inhibition of CYP1A1 microsomal activity was observed in the presence of MSBE (10-20 μg/ml). We can conclude that besides its potent antioxidant activity previously reported, MSBE may also exert a chemoprotective effect due to its capacity to inhibit CYP activity.

An Evaluation of the Mode of Action Framework for MutagenicCarcinogens Case Study II: Chromium (VI).

EPA Science Inventory

In response to the 2005 revised U.S Environmental Protection Agency’s (EPA) Cancer Guidelines, a strategy is being developed to include all mutagenicity and other genotoxicity data with any additional information to determine whether a carcinogen operates through a mutagenic mode...

NASA Ames Arc Jets and Range, Capabilities for Planetary Entry

NASA Technical Reports Server (NTRS)

Fretter, Ernest F.

2005-01-01

NASA is pursuing innovative technologies and concepts as part of America's Vision for Space Exploration. The rapidly emerging field of nanotechnology has led to new concepts for multipurpose shields to prevent catastrophic loss of vehicles and crew against the triple threats of aeroheating during atmospheric entry, radiation (Solar and galactic cosmic rays) and Micrometorid/Orbital Debris (MMOD) strikes. One proposed concept is the Thermal Radiation Impact Protection System (TRIPS) using carbon nanotubes, hydrogenated carbon nanotubes, and ceramic coatings as a multi-use TPS. The Thermophysics Facilities Branch of the Space Technology Division at NASA Ames Research Center provides testing services for the development and validation of the present and future concepts being developed by NASA and national and International research firms. The Branch operates two key facilities - the Range Complex and the Arc Jets. The Ranges include both the Ames Vertical Gun Range (AVGR) and the Hypervelocity Free Flight (HFF) gas guns best suited for MMOD investigations. Test coupons can be installed in the AVGR or HFF and subjected to particle impacts from glass or metal particles from micron to _ inch (6.35-mm) diameters and at velocities from 5 to 8 kilometers per second. The facility can record high-speed data on film and provide damage assessment for analysis by the Principle Investigator or Ames personnel. Damaged articles can be installed in the Arc Jet facility for further testing to quantify the effects of damage on the heat shield s performance upon entry into atmospheric environments.

Peregrine Rocket Motor Test at the Ames Outdoor Aerodynamic Rese

NASA Image and Video Library

2017-02-15

Hunjoo Kim, NASA JPL (Left) and Ashley Karp, NASA JPL (Right) attaching heat sensors the Peregrine Hybrid Rocket Engine prior to its test at the Outdoor Aerodynamic Research Facility (OARF, N-249) at NASA’s Ames Research Center.

NASA/Ames Research Center's science and applications aircraft program

NASA Technical Reports Server (NTRS)

Hall, G. Warren

1991-01-01

NASA-Ames Research Center operates a fleet of seven Science and Applications Aircraft, namely the C-141/Kuiper Airborne Observatory (KAO), DC-8, C-130, Lear Jet, and three ER-2s. These aircraft are used to satisfy two major objectives, each of equal importance. The first is to acquire remote and in-situ scientific data in astronomy, astrophysics, earth sciences, ocean processes, atmospheric physics, meteorology, materials processing and life sciences. The second major objective is to expedite the development of sensors and their attendant algorithms for ultimate use in space and to simulate from an aircraft, the data to be acquired from spaceborne sensors. NASA-Ames Science and Applications Aircraft are recognized as national and international facilities. They have performed and will continue to perform, operational missions from bases in the United States and worldwide. Historically, twice as many investigators have requested flight time than could be accommodated. This situation remains true today and is expected to increase in the years ahead. A major advantage of the existing fleet of aircraft is their ability to cover a large expanse of the earth's ecosystem from the surface to the lower stratosphere over large distances and time aloft. Their large payload capability allows a number of scientists to use multi-investigator sensor suites to permit simultaneous and complementary data gathering. In-flight changes to the sensors or data systems have greatly reduced the time required to optimize the development of new instruments. It is doubtful that spaceborne systems will ever totally replace the need for airborne science aircraft. The operations philosophy and capabilities exist at NASA-Ames Research Center.

Mutagenicity of Diesel and Soy Biodiesel Exhaust Particles

EPA Science Inventory

Mutagenicity Of Diesel And Soy Biodiesel Exhaust Particles E Mutlua,b' SH Warrenb, PP Matthewsb, CJ Kingb, B Prestonc, MD Haysb, DG Nashb,ct, WP Linakb, MI Gilmourb, and DM DeMarinib aUniversity of North Carolina, Chapel Hill, NC bU.S. Environmental Agency, Research Triangle Pa...

Template properties of mutagenic cytosine analogues in reverse transcription

PubMed Central

Suzuki, Tetsuya; Moriyama, Kei; Otsuka, Chie; Loakes, David; Negishi, Kazuo

2006-01-01

We have studied the mutagenic properties of ribonucleotide analogues by reverse transcription to understand their potential as antiretroviral agents by mutagenesis of the viral genome. The templating properties of nucleotide analogues including 6-(β-D-ribofuranosyl)-3,4-dihydro-8H-pyrimido[4,5-c](1,2)oxazin-7-one, N4-hydroxycytidine, N4-methoxycytidine, N4-methylcytidine and 4-semicarbazidocytidine, which have been reported to exhibit ambiguous base pairing properties, were examined. We have synthesized RNA templates using T3 RNA polymerase, and investigated the specificity of the incorporation of deoxyribonucleoside triphosphates opposite these cytidine analogues in RNA by HIV and AMV reverse transcriptases. Except for N4-methylcytidine, both enzymes incorporated both dAMP and dGMP opposite these analogues in RNA. This indicates that they would be highly mutagenic if present in viral RNA. To study the basis of the differences among the analogues in the incorporation ratios of dAMP to dGMP, we have carried out kinetic analysis of incorporation opposite the analogues at a defined position in RNA templates. In addition, we examined whether the triphosphates of these analogues were incorporated competitively into RNA by human RNA polymerase II. Our present data supports the view that these cytidine analogues are mutagenic when incorporated into RNA, and that they may therefore be considered as candidates for antiviral agents by causing mutations to the retroviral genome. PMID:17130163