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T J Hughes

Publications and source records attributed to T J Hughes.

At least 19 recordsLinked to original sources
PubMed2000

Comparison of the mutagenic specificity induced by four nitro-group-containing aromatic amines in Salmonella typhimurium his genes.

Four nitrated aromatic amines (2-nitro-p-phenylenediamine [2NPD], 3-nitro-o-phenylenediamine [3NPD], 4-nitro-o-phenylenediamine [4NPD] and 4,4'-dinitro-2-biphenylamine [DNBA]) are direct-acting mutagens in Salmonella typhimurium strain TA100. These compounds were tested further using the Xenometrix strains of S. typhimurium: TA7001, TA7002, TA7003, TA7004, TA7005, and TA7006, with and without S9 mix in the plate incorporation assay. The direct-acting mutagenicity of 2NPD, 4NPD, and DNBA was detected with TA7002, TA7004 and TA7005. 2NPD and DNBA showed some activity in TA7006; DNBA also showed some activity in TA7003. Mutagenicity was generally decreased in these strains when S9 was added. 3NPD was mutagenic in TA7004 without S9 and in TA7005 with and without S9. These data suggest that 2NPD, 4NPD and DNBA induced TA-->AT and CG-->AT transversions as well as GC-->AT transitions in the his gene. 3NPD induced CG-->AT transversions and GC-->AT transitions. 2NPD and DNBA also induced a small portion of CG-->GC transversions.

Amines↗
PubMed1999

Effect of exercise on hemodynamic conditions in the abdominal aorta.

PURPOSE: The beneficial effect of exercise in the retardation of the progression of cardiovascular disease is hypothesized to be caused, at least in part, by the elimination of adverse hemodynamic conditions, including flow recirculation and low wall shear stress. In vitro and in vivo investigations have provided qualitative and limited quantitative information on flow patterns in the abdominal aorta and on the effect of exercise on the elimination of adverse hemodynamic conditions. We used computational fluid mechanics methods to examine the effects of simulated exercise on hemodynamic conditions in an idealized model of the human abdominal aorta. METHODS: A three-dimensional computer model of a healthy human abdominal aorta was created to simulate pulsatile aortic blood flow under conditions of rest and graded exercise. Flow velocity patterns and wall shear stress were computed in the lesion-prone infrarenal aorta, and the effects of exercise were determined. RESULTS: A recirculation zone was observed to form along the posterior wall of the aorta immediately distal to the renal vessels under resting conditions. Low time-averaged wall shear stress was present in this location, along the posterior wall opposite the superior mesenteric artery and along the anterior wall between the superior and inferior mesenteric arteries. Shear stress temporal oscillations, as measured with an oscillatory shear index, were elevated in these regions. Under simulated light exercise conditions, a region of low wall shear stress and high oscillatory shear index remained along the posterior wall immediately distal to the renal arteries. Under simulated moderate exercise conditions, all the regions of low wall shear stress and high oscillatory shear index were eliminated. CONCLUSION: This numeric investigation provided detailed quantitative data on the effect of exercise on hemodynamic conditions in the abdominal aorta. Our results indicated that moderate levels of lower limb exercise are necessary to eliminate the flow reversal and regions of low wall shear stress in the abdominal aorta that exist under resting conditions. The lack of flow reversal and increased wall shear stress during exercise suggest a mechanism by which exercise may promote arterial health, namely with the elimination of adverse hemodynamic conditions.

Aorta, Abdominal↗
PubMed1998

Genotoxicity of industrial wastes and effluents.

In excess of several million pounds of genotoxic and/or carcinogenic industrial wastes are released into the U.S. environment each year. Chemical characterization of these waste materials can rarely provide an adequate assessment of their genotoxicity and potential hazard. Bioassays do not require prior information about chemical composition and can effectively assess the genotoxicity of complex waste materials. The most commonly used genotoxicity assay has been the Salmonella mutagenicity assay. Results with this system have shown that the genotoxic potency of industrial wastes can vary over 10 orders of magnitude, from virtually nondetectable to highly potent. Industries employing similar industrial processes generally release wastes of similar potency. Extremely high potency wastes include those from furazolidone and nitrofurfural production. Pulp and paper mills, steel foundries, and organic chemical manufacturing facilities also discharge wastes of noteworthy potency. Treatment and remediation of some wastes, such as pulp and paper mill effluents, have been shown to reduce or eliminate genotoxicity. However, in other cases, treatment and remediation have been shown to enhance genotoxicity, such as for fungal treatment of oils. Analyses of samples collected from areas known to receive industrial wastes and effluents have shown that genotoxins can accumulate in the receiving environment and have adverse effects on indigenous biota. The evaluation of hazardous wastes and effluents by genotoxicity assays may provide data useful not only for hazard identification but for comparative risk assessment.

Animals↗
PubMed1998

Genotoxicity of bioremediated soils from the Reilly Tar site, St. Louis Park, Minnesota.

An in vitro approach was used to measure the genotoxicity of creosote-contaminated soil before and after four bioremediation processes. The soil was taken from the Reilly Tar site, a closed Superfund site in Saint Louis Park, Minnesota. The creosote soil was bioremediated in bioslurry, biopile, compost, and land treatment, which were optimized for effective treatment. Mutagenicity profiles of dichloromethane extracts of the five soils were determined in the Spiral technique of the Salmonella assay with seven tester strains. Quantitative mutagenic responses in the plate incorporation technique were then determined in the most sensitive strains, YG1041 and YG1042. Mutagenic potency (revertants per microgram extract) in YG1041 suggested that compost, land treatment, and untreated creosote soil extracts were moderately mutagenic with Arochlor-induced rat liver (S9) but were nonmutagenic without S9. However, the bioslurry extract was strongly mutagenic and the biopile extract was moderately mutagenic either with or without S9. A similar trend was obtained in strain YG1042. The strong mutagenic activity in the bioslurry extract was reduced by 50% in TA98NR, which suggested the presence of mutagenic nitrohydrocarbons. Variation in reproducibility was 15% or less for the bioassay and extraction procedures. Bioavailability of mutagens in the biopile soil was determined with six solvents; water-soluble mutagens accounted for 40% of the total mutagenic activity and they were stable at room temperature. The mutagenic activity in the bioslurry and biopsile samples was due to either the processes themselves or to the added sludge/manure amendments. The in vitro approach was effective in monitoring bioremediated soils for genotoxicity and will be useful in future laboratory and in situ studies.

Animals↗
PubMed1998

Bioassay-directed fractionation and chemical identification of mutagens in bioremediated soils.

Soil from a Superfund site (Reilly Tar Site, St. Louis Park, Minnesota) contaminated with polycyclic aromatic hydrocarbons (PAHs) from creosote was treated with several bioremediation technologies including bioslurry (BS), biopile (BP), compost (CMP), and land treatment (LT). These treatment technologies are being evaluated in pilot scale laboratory systems by the U.S. Environmental Protection Agency's National Risk Management Research Laboratory in Cincinnati, Ohio. To evaluate the genotoxicity and identify the mutagens in the soil before and after the various treatments, fractionated extracts of five soils were bioassayed for mutagenic activity with a microsuspension modification of the Salmonella histidine reversion assay. Soils were extracted by sonication using dichloromethane (DCM). The five extracts were fractionated in triplicate (two for bioassay and one for chemical analysis) by reverse-phase high-performance liquid chromatography (HPLC) using hexane/DCM/methanol, and the fraction for bioassay were solvent-exchanged into dimethyl sulfoxide by nitrogen evaporation. Forty HPLC fractions for each sample were bioassayed in strain YG1041 with and without exogenous liver metabolic activation. As shown in a companion paper, the mutagenicity of two treatments (BS and BP) was significantly greater than the mutagenicity of the untreated soil. Mutagenic fractions (> 500 revertants) were analyzed by gas chromatography/mass spectrometry (GC/MS). PAH analysis of the soils indicated that all treatments were effective in reducing the total PAH concentration (48-74%). Qualitative GC/MS analysis of the mutagenic fractions from the BS and BP treatments indicated that they contained azaarenes, which are mutagens. The CMP and LT processes were the most effective and least toxic bioremediation procedures based on mutagenic potency and chemical analysis. This research demonstrated that the combination of bioassays and chemical analysis provided a more accurate determination of toxicity in these complex environmental mixtures.

Biological Assay↗
PubMed1997

Development of a standard reference material for diesel mutagenicity in the Salmonella plate incorporation assay.

The present study documents the mutagenicity of a new National Institute of Standards and Technology (NIST) standard reference material (SRM) in the Salmonella plate incorporation assay. This study is in response to a previous recommendation by the World Health Organization to develop large batches of new SRMs for biological and chemical research. SRM 1975 is a dichloromethane (DCM) extract of 5.6 kg of filter-collected combustion particulate matter (SRM 2975) from operating forklifts with diesel engines. The mutagenicity and a summary of the related chemical analysis of mutagens in SRM 1975 is presented in this paper, and are available from the NIST. Mutagenicity test conditions were: Salmonella typhimurium TA98, TA100 (standard strains); TA98NR, TA100NR (nitroreductase (NR) gene deficient); and YG1021 and YG1026 (NR gene addition); 10 dose levels in the linear portion of the dose-response curve; duplicate plates per dose; and S9 at 6.4% or 1.1 mg of protein/plate. Four rounds of testing were conducted. Rounds were conducted at least 1 week apart. Slopes (revertants/microg) were calculated by the linear regression rejection model of Bernstein and by the Stead and Krewski models which analyze non-linear data. The GeneTox Manager software package developed at the EPA was used to record the data and calculate the slopes. Results demonstrated: (1) the ranking of slopes without S9 was: YG1021 > TA98 > TA98NR > YG1026 > TA100 > TA100NR in all three statistical models; (2) the mutagenic activity of SRM 1975 was significantly increased by the presence of the NR gene; (3) the slope values for the TA100 series were significantly less than for the TA98 series; (4) in general, the addition of the S9 significantly reduced mutagenic activity; (5) the mutagenic activity of the SRM 1975 was stable over time and variability was low (generally less than 20% in slope values over the 4 rounds); and (6) agreement of the slope values among the three models was excellent due to the linear nature of the data. These data will be useful in ranking other diesel and air samples for mutagenic activity, for quality assurance of data generated in different laboratories, for quality control within a laboratory, and as positive control values for future air and automotive emission studies.

Mutagenicity Tests↗
PubMed1997

Chemical and mutagenic analysis of volatile organic compounds in Raleigh air samples at three different elevations before, during, and after Hurricane Gordon.

Volatile organic compounds (VOCs) were collected and measured at a television tower 10 km southeast of downtown Raleigh, North Carolina at three different levels (Surface, < 1 m; Mid, 240 m; and Top, 433 m) during the summer and fall of 1994. The combined presence of ozone, arenes, and nitrogen oxides (NOx) suggested possible nitration of arenes during atmospheric mixing. Air samples, therefore, were collected using XAD-filled canisters at each level on the tower prior to, during, and after Hurricane Gordon. Collected air samples were Soxhlet extracted and analyzed with the Salmonella typhimurium microsuspension mutagenicity assay using strains YG1021 and YG1026 which are sensitive to nitrarenes. Significant mutagenicity was observed only in the Top and Mid level samples for the post-hurricane, normal weather air samples. Surface samples were not mutagenic, which suggests the long-range transport of these mutagenic nitrarenes.

Air Pollutants↗
PubMed1996

A comparative evaluation of the in vitro penetration performance of the improved Crest complete toothbrush versus the Current Crest complete toothbrush, the Colgate Precision toothbrush and the Oral-B P40 toothbrush.

Removal of plaque and debris from interproximal surfaces during toothbrushing has generally been difficult to achieve, in large part because traditional flat-bristled toothbrushes do not offer good interproximal penetration. As a result, a number of varying bristle designs have been developed, with the rippled-design brush shown to be particularly effective at removing interproximal plaque. Recently, an existing brush, the original Crest Complete, was modified to offer a more deeply rippled version. This study evaluated the interproximal penetration of four bristle designs: rippled pattern (original Crest Complete), deeper rippled pattern (improved Crest Complete), multi-level (Colgate Precision), and flat-tufted (Oral-B P40). The study used a previously reported in vitro model for determining interproximal penetration of manual toothbrushes (J Clin Dent 5:27-33, 1994). In order to effectively mimic the in-use characteristics of toothbrushing, this model is based on analysis of videotaped consumer brushing habits, tooth morphology, and in vivo plaque tenacity characteristics and uses the three most predominantly used brushing techniques (circular, up-and-down, and back-and-forth, with the brush held at both 45 and 90 degrees to the tooth surface). In addition, the model's brush stroke length, brush force, and brush speed are likewise based on analysis of consumer brushing patterns. The results of the study indicate that the new Crest Complete with deeper rippled bristles provided significantly superior (p < or = 0.05) interproximal penetration than the Colgate Precision and Oral-B brushes overall and for three of the four brush strokes tested. In addition, the new Crest Complete was found to provide significantly superior interproximal penetration to the original Crest Complete overall and in circular and up-and-down strokes, and the original Crest Complete provided superior overall interproximal penetration to the Colgate and Oral-B brushes.

Analysis of Variance↗
PubMed1991

Assessing the use of known mutagens to calibrate the Salmonella typhimurium mutagenicity assay: I. Without exogenous activation.

There has been an increasing need in genetic toxicology to progress from strictly qualitative tests to more quantitative tests. This, in turn, has increased the need to develop better quality assurance and comparative bioassay methods. In this paper, two laboratories tested 10 Salmonella mutagens in order to determine the usefulness of selected chemicals as potential reference materials to calibrate the Salmonella assay. If variance within a bioassay is sufficiently low and the rankings of the compounds are of acceptable consistency, the chemicals later could be evaluated for use as standard control compounds, as audit materials, and as standard reference materials for comparative bioassay efforts. The results demonstrated that the chosen chemicals (with the possible exception of dimethylcarbamylchloride) provide such consistent results in the Salmonella mutagenicity bioassay that they can be used for semi-quantitative calibration and as possible bioassay controls, special audit chemicals, and potentially as reference standards in comparative bioassay efforts. Reference standards, whether used as audit materials or in comparative bioassays, must be used concurrently with the test substances of interest; used without bias; used in a standardized, highly controlled bioassay; and be tested across an appropriate dose range. The study also shows that when these compounds are used as reference standards much care must be given to the number and spacing of doses if highly reproducible slope values are to be generated. We recommend use of a pilot test to establish a dose range for definitive tests and the placement of doses for the definitive tests within the first half of the linear dose-response curve. For appropriate comparisons, one should replicate the tests using the defined dose range and analyze the results in a non-biased statistical manner.

Calibration↗
PubMed1991

Assessing the use of known mutagens to calibrate the Salmonella typhimurium mutagenicity assay: II. With exogenous activation.

In order to determine the usefulness of selected chemicals as potential reference materials for calibrating the Salmonella assay, two laboratories tested a series of Salmonella mutagens that require exogenous activation. When the variance for individual substances within a bioassay is sufficiently low and the rankings of those substances are of acceptable consistency, they can later be evaluated for use as standard control compounds, as audit materials, and as standard reference materials for comparative bioassay efforts. The purpose of this project, therefore, was to evaluate the variability in the mutagenic response of potential reference chemicals that require exogenous metabolic activation in the standard plate-incorporation Salmonella mutagenicity assay, and to develop ranking criteria for mutagenic activity based on these data. Ten indirect-acting mutagens were tested in two laboratories using Salmonella typhimurium TA100 and an Aroclor-induced rat liver S9. Each laboratory conducted four definitive testing rounds. A different batch of S9 was utilized for every two rounds. Of the 10 chemicals tested only 2-anthramine had a mean slope value greater than 1000 revertants/micrograms. Three chemicals had slope values between 1000 and 100; and five chemicals had slope values between 100 and 10. The remaining compound, 9,10-dimethyl-1,2-benz[a]anthracene, could not be placed into a single category because it had slope values on either side of 100 revertants per mg. Coefficients of variance were low (i.e., below 25% in most cases). The low variability achieved in this study may be accounted for by two parameters of the study. First, based on Claxton et al. (1991a) and the S9 optimization for three compounds, the amount of S9 was calibrated to a set amount of protein per plate (1.1 mg/plate). Secondly, the 10 test doses were placed in the initial, linear, nontoxic portion of the dose-response curves. The use of ten closely spaced, nontoxic doses allowed for a more accurate estimate of the slope.

Animals↗
PubMed1991

Airway protection by the laryngeal mask. A barrier to dye placed in the pharynx.

Methylene blue was placed in the pharynx of 64 patients undergoing anaesthesia with the laryngeal mask. No leak of dye into the larynx was detected on fibreoptic inspection of the inside of the mask in any subject. The use of the laryngeal mask as a means of protecting the airway during procedures such as minor nasal operations is therefore supported.

Airway Obstruction↗
PubMed1989

A genotoxic assessment of environmental tobacco smoke using bacterial bioassays.

Recently, the National Research Council in the U.S.A. stated that laboratory studies of environmental tobacco smoke (ETS) should be important in identifying ETS carcinogens, their concentrations in typical daily environments, and in understanding how these compounds contribute to ETS dose-response relationships. This paper demonstrates that integrated chemical and bacterial mutagenicity information can be used to identify ETS genotoxicants, monitor human exposure, and make comparative assessments. Approximately 1/3 of the ETS constituents for which there is quantitative analytical chemistry information also have associated genotoxicity information. For example, 11 of the quantitated compounds are animal carcinogens. Work presented in this paper demonstrates that both the nonparticle-bound semivolatile and the particulate-bound organic material contain bacterial mutagens. These ETS organics give an equivalent of approximately 86,000 revertants per cigarette. In addition, this article summarized efforts to estimate ETS bacterial mutagenicity, to use bacterial tests for the monitoring of ETS-impacted indoor environments, and to use bacterial assays for the direct monitoring of human exposure.

Microbial Sensitivity Tests↗
PubMed1989

Preliminary molecular analysis of the TK locus in L5178Y large- and small-colony mouse lymphoma cell mutants.

Mouse lymphoma cells of the L5178Y TK+/- -3.7.2C line were exposed to sidestream and mainstream cigarette smoke condensates (CSC). Cells which survived the trifluorothymidine (TFT) challenge fell in 2 classes: large- and small-colony formers. Southern blot analysis of NcoI-digested DNA from mutant colonies yielded 2 distinct restriction fragment banding patterns when probed with the thymidine kinase (TK) cDNA clone pMtk4. One such pattern was composed of 4 bands at 6.4, 5.5, 4.7 and 2.9 kilobase pairs (kb) and was identical to that of TK+/- controls. A second pattern differed from the first only in the absence of the 6.4-kb band. The majority (83/95) of both large and small colonies derived from cells exposed to CSC exhibited restriction fragment banding patterns lacking the 6.4-kb band. The data from the present study suggest that there is no association between mutant colony size and the presence of the 6.4-kb NcoI restriction fragment at the TK locus in the mouse lymphoma mutants analyzed.

Animals↗
PubMed1988

Mutagenic activity of some coffee flavor ingredients.

The mutagenicity of 4 coffee flavor ingredients (chlorogenic acid, caffeic acid, pyrazine, and trigonelline) was evaluated in the Salmonella plate incorporation assay and mouse lymphoma L5178Y TK +/- assay. Two of the compounds, pyrazine and trigonelline, were negative in both assays. The other two compounds, caffeic acid and chlorogenic acid, were positive in the mouse lymphoma assay but negative in the Salmonella assay.

Alkaloids↗
PubMed1987

Vaporization technique to measure mutagenic activity of volatiles organic chemicals in the Ames/Salmonella assay.

The purpose of this research was to develop and characterize a sensitive test method to detect mutagenic activity of volatile liquid organic chemicals (i.e, volatiles) in the Ames/Salmonella assay. A Tedlar bag vaporization technique was developed, which increased contact time between the volatiles and bacterial test system, circumvented volatilization limitations in the standard plate incorporation and preincubation methods, allowed chemical analysis during incubation, and was flexible in design. The vaporization technique was evaluated concurrently against the plate incorporation and preincubation techniques with eight liquid volatile mutagens in the Ames/Salmonella mutagenicity assay with Salmonella typhimurium strains TA100 and TA102. Results suggested that when volatile organic chemicals with boiling points below 63 degrees C were tested for mutagenic activity, the most sensitive test conditions were the vaporization technique with TA100. GC analysis of epichlorohydrin and butylene oxide concentrations within Tedlar bags suggested that these two chemicals volatilized and were contained in the media after 1 hr of incubation at 37 degrees C. The mutagenic activity of six volatile liquid mutagens was similar in single and triple plate Tedlar bags. Three general test groups of volatile organic chemicals were identified by test data: chemicals which had boiling points below 63 degrees C, for which the vaporization technique was the most sensitive test procedure (ethylene, propylene, and butylene oxides and methylene chloride); chemicals which had boiling points from 107 degrees to 132 degrees C, for which the vaporization technique was still useful, but where sensitivity was only slightly increased over the preincubation technique (1-bromo-2-chloroethane, epichlorohydrin, and ethylene dibromide); and 3) a chemical which had a boiling point at 194 degrees C, where the preincubation technique was the most appropriate test method (styrene oxide).

Animals↗