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Biomedical subjects

J M Benson

Publications and source records attributed to J M Benson.

At least 91 records · Page 5Linked to original sources
PubMed1985

New approaches for the evaluation of pulmonary toxicity: bronchoalveolar lavage fluid analysis.

Analysis of bronchoalveolar lavage fluid (BAL) is an effective method of detecting an inflammatory response in the lungs of animals in toxicological studies. Alterations in BAL that are the most sensitive indications of an inflammatory response are an increased content of serum proteins and an influx of neutrophils (PMNs). Elevation of the cytoplasmic enzyme lactate dehydrogenase (LDH) is a useful indicator of cytotoxicity. The pulmonary inflammatory response to particles (either mineral dusts or soot) in the lung includes greatly increased activities of such lysosomal enzymes as beta-glucuronidase and beta-N-acetylglucosaminidase in BAL. Examination of alterations in BAL in rats and mice during chronic exposure to high levels of diluted diesel exhaust revealed that steadily increasing levels of LDH, beta-glucuronidase, and hydroxyproline in BAL correlated better with the development of pulmonary fibrosis than did measures of an inflammatory response (protein, PMNs). Analysis of BAL has proven useful, both for detection of lung injury in toxicological screening tests and for determination of the mechanisms of developing chronic lung disease. Future work shows promise of developing assays for BAL analysis to identify the specific site or type of pulmonary injury present.

Animals↗
PubMed1985

Effects of the long-term depletion of reduced glutathione in mice administered L-buthionine-S,R-sulfoximine.

Previous methods to deplete in vivo concentrations of reduced glutathione (GSH) have not been able to lower tissue GSH levels for extended periods, have been toxic, and can alter the metabolism of xenobiotics. A possible alternative to lower in vivo concentrations of GSH may be the use of buthionine-S,R-sulfoximine (BSO) in the drinking water of laboratory animals to inhibit the biosynthesis of GSH. It has been previously reported that 20 mM BSO in the drinking water given to mice was able to lower GSH levels in a variety of tissues after 15 days. In order to more fully characterize the in vivo depletion of GSH in tissues by ingestion of BSO and determine if this method would be suitable in studies requiring depressed levels of GSH for extended periods, we added different amounts of this agent to the drinking water given to mice for various times up to 28 days. We found that ingested BSO at the highest concentration used in drinking water (30 mM) was able to maximally lower GSH concentrations in mouse lungs, lung lavage fluid, liver, kidneys, and blood to 59.0 +/- 3.6%, 35.0 +/- 5.1%, 44.3 +/- 1.5%, 69.5 +/- 3.9%, and 70.0 +/- 6.0% of control mice, respectively, for up to 28 days. These lowered concentrations of tissue GSH returned to control levels after mice were returned to untreated drinking water for 7 days. The potential toxicity of such treatments was also evaluated. Levels of alkaline phosphatase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, glutathione peroxidase, and glutathione reductase in lungs and lung lavage fluid, and total and differential cell counts from lung lavage fluid were not different between control and BSO-treated mice. This showed that BSO treatment did not produce indications of lung injury as measured by these biochemical parameters. Serum aspartyl transferase and gamma-glutamyl transpeptidase activities were unaffected by the BSO treatments, indicating normal liver functions. Lung and liver cytochrome P-450 concentrations were also not different between controls and BSO-treated animals. Thus, BSO in the drinking water of mice was able to effectively lower in vivo levels of GSH without eliciting acute toxic responses.

Animals↗
PubMed1984

Evaluation of the genotoxicity of process stream extracts from a coal gasification system.

Extracts of three complex organic environmental mixtures, two from an experimental coal gasifier (a raw gas and a clean gas sample) and one from a coke oven main, were examined for genotoxicity. Three short-term genotoxicity assay systems were used: Ames Salmonella typhimurium reverse mutation assay, Chinese hamster ovary cell/hypoxanthine-guanine phosphoribosyl transferase (CHO/HGPRT) gene locus mutation assay, and the Chinese hamster lung primary culture/sister chromatid exchange (CHL/SCE) assay. Aroclor-1254-induced rat liver homogenate fraction (S-9) was required to observe genotoxicity in both gene locus mutation assays (CHO/HGPRT and Ames). The relative survival of CHO cells exposed to extracts was highest in cells exposed to clean gas samples, with the raw gas sample being the most cytotoxic either with or without the addition of S-9. All three complex mixtures induced sister chromatid exchanges in primary lung cell cultures without the addition of S-9. The relative genotoxicity ranking of the samples varied between the mammalian and prokaryotic assay systems. Coke oven main extract produced fewer revertants in bacteria than the raw gas sample. However, the coke oven main extract was more genotoxic in the two eukaryotic systems (CHL/SCE and CHO/HGPRT) than was the raw gas sample. The results of all three assays indicate that the cleanup process used in the experimental gasifier was effective in decreasing the genotoxic materials in the process stream. These data also reemphasize the necessity of evaluating genotoxicity of complex mixtures in a variety of short-term systems.

Air Pollutants, Occupational↗
PubMed1984

The induction of sister chromatid exchanges by environmental pollutants: relationship of SCE to other measures of genetic damage.

Sister chromatid exchanges (SCEs), induced by environmental pollutants from fossil fuel use, were measured in 2 cell systems, Chinese hamster ovary (CHO) cells and Chinese hamster primary lung cell cultures. The frequency of SCEs induced in these cell systems was related to other measures of genetic damage, namely mutations in CHO cells at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) gene locus and in bacteria (Salmonella mutagenicity test TA-98), produced by the same pollutants. The pollutants were divided into 2 classes: those produced in oxidizing combustion environments--extracts of particles from light-duty diesel cars, spark-ignition cars, and an automotive tunnel; and those produced in reducing environments--extracts from coke oven mains and condensates from a low BTU coal gasifier obtained either before or after cleanup of the process stream. Sister chromatid exchanges were induced by all pollutants without the addition of a rat liver microsomal fraction (S-9 mix), whereas S-9 mix was required to induce a positive response in the CHO/HGPRT assay for all pollutants. The pollutants produced in a reducing environment required metabolic activation by S-9 mix to be mutagenic in the Salmonella mutation assay. The addition of S-9 mix to pollutants produced in an oxidizing environment reduced the response in the Salmonella test. The relative genotoxic potency for each pollutant was determined for all 3 endpoints. The slopes of dose-response curves for each pollutant were plotted for each assay to compare relative potency. When the bacterial mutagenicity test was compared to either mammalian cell assay, SCE or CHO/HGPRT, there was little correlation between relative potencies. However, the data indicated that the responses in the 2 mammalian cell assays, SCE and CHO/HGPRT, showed similar relative responses to the pollutants. Differences in the requirement for S-9 mix seem to be related to both the chemical nature of the mixture and the endpoint measured. Differences in responses are related not only to cell type but also to chemical composition of the complex pollutants.

Air Pollutants↗
PubMed1984

Toxicological and chemical characterization of the process stream materials and gas combustion products of an experimental low-btu coal gasifier.

The process gas stream of an experimental pressurized McDowell-Wellman stirred-bed low-Btu coal gasifier, and combustion products of the clean gas were characterized as to their mutagenic properties and chemical composition. Samples of aerosol droplets condensed from the gas were obtained at selected positions along the process stream using a condenser train. Mutagenicity was assessed using the Ames Salmonella mammalian microsome mutagenicity assay (TA98, with and without rat liver S9). All materials required metabolic activation to be mutagenic. Droplets condensed from gas had a specific mutagenicity of 6.7 revertants/microgram (50,000 revertants/liter of raw gas). Methylnaphthalene, phenanthrene, chrysene, and nitrogen-containing compounds were positively identified in a highly mutagenic fraction of raw gas condensate. While gas cleanup by the humidifier-tar trap system and Venturi scrubber led to only a small reduction in specific mutagenicity of the cooled process stream material (4.1 revertants/microgram), a significant overall reduction in mutagenicity was achieved (to 2200 revertants/liter) due to a substantial reduction in the concentration of material in the gas. By the end of gas cleanup, gas condensates had no detectable mutagenic activity. Condensates of combustion product gas, which contained several polycyclic aromatic compounds, had a specific mutagenicity of 1.1 revertants/microgram (4.0 revertants/liter). Results indicate that the process stream material is potentially toxic and that care should be taken to limit exposure of workers to the condensed tars during gasifier maintenance and repair and to the aerosolized tars emitted in fugitive emissions. Health risks to the general population resulting from exposure to gas combustion products are expected to be minimal.

Air Pollutants↗
PubMed1983

Hemoglobin Evanston: alpha 14(A12) Trp leads to Arg. A variant hemoglobin associated with alpha-thalassemia-2.

Hb Evanston (alpha 14 Trp leads to Arg) was detected on cellulose acetate at pH 8.4 as a band with an electrophoretic mobility similar to that of Hb S. In addition, a band migrating cathodic to Hb A2 suggested the presence of a variant Hb A2 with a substitution in the alpha-chain, a fact that was later confirmed by structural analysis. An unusual feature of Hb Evanston is its low percentage; less than 10% occurs in the hemolysate. Studies indicate that the variant is not unstable, but there appears to be a defect in globin-chain synthesis. Gene mapping also shows that it is associated with the alpha-thalassemia-2 gene. The variant has high oxygen affinity with normal cooperativity and a normal Bohr effect. The combination of Hb Evanston with alpha-thalassemia-2 produced anemia in this black family.

Female↗
PubMed1983

Metabolism of phenanthridine to phenanthridone by rat lung and liver microsomes after induction with benzo[a]pyrene and Aroclor.

The comparative metabolism of phenanthridine (3,4-benzoquinoline) by rat lung and liver microsomes has been investigated. The array of metabolites produced by induced lung and liver are qualitatively similar. Phenanthridone has been identified as a phenanthridine metabolite produced by induced rat liver and lung. Phenanthridone is directly mutagenic in Salmonella tester strain TA-98 while phenanthridine is not. Although phenanthridone is more mutagenic than phenanthridine after incubation with rat liver 9000g supernatant fraction, it is less cytotoxic to Chinese hamster ovary cells in vitro.

Animals↗
PubMed1983

Evaluation of an exposure system using cells grown on collagen gels for detecting highly volatile mutagens in the CHO/HGPRT mutation assay.

Chinese hamster ovary (CHO) cells were grown on hydrated collagen gels, the overlaying medium removed leaving the cells at an air/collagen interface, and the cells exposed to a dynamic flow of ethylene oxide. Increases in CHO cell mutant frequency and decreases in cell viability were observed. To establish if the exposure system could be simplified, cells were exposed in sealed bottles (static system) to ethylene oxide. No substantial changes in cytotoxicity, mutant frequency, or effective concentration were noted when comparing static versus dynamic exposure systems. The general usefulness of the exposure system using cells grown on collagen gels was evaluated in a static system using propylene oxide and 1,2-dichloroethane, both of which were found to be mutagenic and cytotoxic. Comparatively, the exposure of cells by the collagen gel method was as effective in detecting genotoxic damage as were conventional methods (cells covered with medium) using cells grown on glass substrates. The exposure of CHO cells on collagen gels to highly volatile mutagens was simple and inexpensive, and may be generally useful in the detection of gaseous or volatile mutagens.

Animals↗
PubMed1983

Cytotoxicity and mutagenicity of vapor-phase pollutants in rat lung epithelial cells and Chinese hamster ovary cells grown on collagen gels.

Lung epithelial cell (cell line designated LEC) and Chinese hamster ovary (CHO) cells were grown on hydrated collagen gels and exposed directly to toxic vapor-phase pollutants. The cells were exposed to graded concentrations of phenol, formaldehyde, a volatile fraction of process stream material from an experimental coal gasifier and the nonparticulate, vapor phase of diesel engine exhaust. During exposures, the cells were maintained at an air/collagen interface by removing the medium overlying the hydrated collagen gel. Morphological changes indicative of cell retraction were found in LEC cell cultures exposed to phenol, formaldehyde, or diesel exhaust. Damage following exposure to the toxicants was quantitated in LEC and CHO cells by Trypan blue dye exclusion, a measure of plasma membrane integrity. Clone-forming ability was also used to measure cell survival in CHO cells. When measured by Trypan blue dye exclusion, phenol (EC50 = 2.1 mg/l) caused membrane damage to LEC cells but not CHO cells, while formaldehyde (EC50 = 31 and 42 micrograms/l for LEC and CHO, respectively) and diesel exhaust (EC50 = 11 and 29% of tailpipe exhaust in LEC and CHO cells, respectively) caused damage to both cell types. No cytotoxicity was observed in LEC or CHO cells exposed to the fraction from the coal gasifier. Essentially no mutagenic activity was associated with the exposure of CHO cells to formaldehyde or the vapor phase of diesel exhaust. Mutagenic activity was found in CHO cells exposed to ethylene oxide, the positive control. The results of this study indicate that mammalian cells grown on collagen gels can readily be exposed to vapors of chemicals and chemical mixtures. The cell exposure system may be generally useful in the analysis of toxic damage to mammalian cells resulting from gaseous or vapor-phase pollutants.

Air Pollutants↗
PubMed1983

A simple dynamic flow-through exposure system for assessment of biological activity of complex organic mixtures to mammalian cells in vitro.

A system for in vitro exposure of lung epithelial cells and Chinese hamster ovary cells maintained at an air-medium interface to volatile organic compounds has been developed. The system has been used for exposure of cells to phenol (vapor pressure at 40 degrees C = 1.6 mm Hg) and to a complex mixture of organic compounds (vapor pressure range at 32 degrees C = 0.17 to 269 mm Hg). A linear relationship was found between vapor generator air flow rate (0.25 to 1.0 L/min at 39 degrees C) and exposure chamber phenol concentration. The relationship between generator air flow rate (0.5 to 1.0 L/min at 39 degrees C) and concentration of the complex mixture in the exposure chamber was also linear. Gas chromatographic analyses of chamber exhaust indicated that a majority of the compounds present in the crude mixture had been volatilized and made available to the cells in the chamber. This exposure system appears suitable for screening of complex mixtures of volatile organic pollutants for biological activity in mammalian cells in culture.

Air Movements↗
PubMed1982

Cytochrome P-450-dependent monooxygenases in olfactory epithelium of dogs: possible role in tumorigenicity.

The respiratory tract epithelium of dogs, from the nose to the lungs, was examined for cytochrome P-450 and associated biotransformation activities. In the ethmoturbinates, where olfactory epithelium is located, the amount of cytochrome P-450 was comparable to that in the liver, when measured on the basis of activity per milligram of microsomal protein. The rest of the nasal region also contained large quantities of cytochrome P-450. The presence of these enzymes in the nose may be important in chemical-induced tumorigenesis. The nasal carcinogen hexamethyl-phosphoramide was shown to be metabolized by nasal microsomal enzymes to another nasal carcinogen, formaldehyde.

Animals↗
PubMed1982

Radiation safety.

Radiation safety is rapidly becoming a major concern of every patient. Poor understanding of ionizing radiation and its effects frequently heightens anxiety. The average United States resident receives about 125 mrem of radiation per year from natural background radiation and another 120 mrem from man-made sources. The 240 million x-ray procedures performed annually contribute 90 percent of the man-made portion. It is assumed that the risks of medical radiation are outweighed by the benefits gained from the information obtained. If present in sufficiently high dosage, radiation can have harmful effects, such as induction of leukemia and thyroid malignancy. No deleterious effects have been shown to have been caused by diagnostic radiation. It is reassuring that the risks of medical radiation appear to be quite small compared with other common hazards most people face daily. Careful attention to the use of radiographic safety and protective technique will ensure the lowest possible radiation dose. The physician's discretion in ordering only appropriate and indicated x-ray films will ensure the patients are exposed to the lowest possible amount of radiation.

Female↗