Biomedical subjects

T M Ong

Publications and source records attributed to T M Ong.

At least 37 records · Page 2Linked to original sources

PubMed1991

Antimutagenicity studies of chlorophyllin using the Salmonella arabinose-resistant assay system.

Studies with the arabinose-resistant Salmonella forward mutation assay system were performed to determine the antimutagenic activity of chlorophyllin against the mutagenic activity of aflatoxin B1 (AFB1), 2-aminoanthracene (2AA), benzo[a]pyrene (BaP), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and solvent extracts of coal dust (CD), diesel emission particles (DE), airborne particles (AP), tobacco snuff (TS), black pepper (BP) and red wine (RW). Various concentrations of each chemical and complex mixture extract were assayed for mutagenic activity with and/or without S9 in a preincubation test. One concentration of each chemical and complex mixture extract was then tested with various concentrations of chlorophyllin. Results showed that chlorophyllin, at concentrations of 2.5 mg/plate or less, completely or almost completely inhibited the mutagenicity of 2AA, AFB1, BaP, MNNG and solvent extracts of CD, DE and RW. With concentrations from 1.25 to 5 mg/plate, chlorophyllin inhibited over 50% of the mutagenicity of AP, TS and BP extracts. These results further substantiate the antimutagenic efficacy of chlorophyllin against chemicals and complex mixtures.

Aflatoxin B1↗

PubMed1988

Comparative antimutagenicity of chlorophyllin and five other agents against aflatoxin B1-induced reversion in Salmonella typhimurium strain TA98.

Chlorophyllin was studied for its antimutagenic activity against aflatoxin B1 in Salmonella typhimurium strain TA98 using the plate-incorporation test in the presence of S9 activation. Comparative antimutagenicity between chlorophyllin and certain commonly studied antimutagens (i.e., vitamins A, C, and E, retinoic acid, and beta-carotene) was also examined. A dose-related inhibition of aflatoxin B1 mutagenicity by chlorophyllin was observed, with the mutagenicity being abolished by 860 nmole chlorophyllin per plate. The inhibitory activity of chlorophyllin occurred only when cells were treated concurrently with chlorophyllin and aflatoxin B1. The antimutagenic potency of chlorophyllin was comparable to that of vitamin A and higher than that of retinoic acid and beta-carotene. Vitamins C and E had no effect on aflatoxin B1 mutagenicity under the conditions used. The results of toxicity tests and a reconstruction experiment showed that inhibition of the mutagenicity of aflatoxin B1 by chlorophyllin and the other active agents was due to antimutagenicity.

Aflatoxin B1↗

PubMed1987

Mutagenicity assessment of airborne particles from three polyurethane foam manufacturing facilities.

In conjunction with industrial hygiene surveys, mutagenicity studies were performed for the airborne contaminants in three polyurethane manufacturing plants. Airborne particles were collected on glass-fiber filters with Hi-Vol pumps from different locations in each plant. Gases were collected in multiple-sorbent cartridges. The collected airborne particles and sorbent cartridges were extracted with organic solvents. Each extract was tested for mutagenic activity using Salmonella typhimurium TA98 and TA100. The results showed that airborne particles from all three plants are mutagenic to TA98 with or without S9 activation. The mutagenicity with S9, however, was two to four times higher than that without S9. None of the samples of gases collected on sorbent cartridges showed mutagenic activity.

Air Pollutants, Occupational↗

PubMed1987

Application of SOS umu-test for the detection of genotoxic volatile chemicals and air pollutants.

The SOS umu-test has been used for the detection of DNA-damaging agents. In this system the plasmid pSK1002 carrying a fused gene umuC-lacZ was introduced into Salmonella typhimurium TA1535. The SOS function induced by genotoxic agents is detected by a colorimetric measurement of beta-galactosidase activity encoded by the lacZ gene, which is regulated by the Umu operon. This system was used with modifications to study the SOS function inducibility of volatile chemicals (propylene oxide, methyl bromide, and ethylene dibromide) and air pollutants (diesel emission, welding fumes, and cigarette smoke). Tester cells were exposed directly to the test material. The enzyme activity of the treated cells was measured according to the established procedure. Results of the study showed that all chemicals and pollutants tested induced SOS function in a dose-related manner. These results indicate that the SOS umu-test is potentially useful for the in situ detection of genotoxic agents in occupational settings.

Air Pollutants↗

PubMed1987

Two N-hydroxylaminopurines are highly mutagenic in the ad-3 forward-mutation test in growing cultures of heterokaryon 12 of Neurospora crassa.

3 purine analogs were tested for their mutagenic activities in the ad-3 forward-mutation test in heterokaryon 12 (H-12) of Neurospora crassa. In growing cultures of H-12, the N-hydroxylaminopurines 2-amino-6-N-hydroxylaminopurine (AHA) and 6-N-hydroxylaminopurine (HAP) are potent and strong mutagens, respectively, whereas 2-aminopurine (AP) is a weak mutagen. AHA and HAP are about equally mutagenic at low doses, but AHA is more mutagenic than HAP at high doses. Despite their potent mutagenicity in growing cultures, AHA and HAP are not mutagenic in nongrowing conidia under the conditions of our experiments. AHA is the most potent mutagen tested in the ad-3 forward-mutation test in N. crassa. At the highest dose tested (30 micrograms/ml), it gave an ad-3 mutant frequency of 0.7 X 10(-2), about a 12,000-fold increase over the average spontaneous ad-3 mutant frequency. The potent mutagenicity of AHA may make it (and possibly HAP) especially useful for obtaining specific-locus mutations in other organisms.

2-Aminopurine↗

PubMed1987

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

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.

Dimyristoylphosphatidylcholine↗

PubMed1986

Detection of sister chromatid exchanges induced by volatile genotoxicants.

To test the recently developed method of exposing cells to volatile compounds, phytohemagglutinin-stimulated human peripheral lymphocyte cultures were exposed to gaseous methyl bromide, ethylene oxide, and propylene oxide, as well as diesel exhaust. The cultures were placed in sterile dialysis tubing and inserted into enclosed flasks containing additional culture medium. The test compounds (in gaseous state) were diluted with air and bubbled through the flasks for various lengths of time. The cells were then washed and incubated for a total of 75 h. The harvest was performed according to established procedures, and second-division cells were scored for induction of sister chromatid exchanges (SCEs). The SCE frequency was more than doubled in the cultures treated with ethylene oxide and propylene oxide; methyl bromide also induced SCEs. Cultures treated with diesel exhaust showed an increase in the SCE frequency in cells from two of four donors tested. These results further substantiate the use of this method for detecting the induction of SCEs by airborne genotoxins.

Cells, Cultured↗

PubMed1986

Chlorophyllin: a potent antimutagen against environmental and dietary complex mixtures.

Chlorophyllin, the sodium and copper salt of chlorophyll, was tested for its ability to inhibit the mutagenic activity of a variety of complex mixtures--extracts of fried beef, fried shredded pork, red grape juice, red wine, cigarette smoke, tobacco snuff, chewing tobacco, airborne particles, coal dust and diesel emission particles--in strain TA98 of Salmonella typhimurium. Chlorophyllin was highly effective against the mutagenicity (90-100% inhibition) of 8 of these 10 mixtures. The mutagenicity of the other 2 mixtures was inhibited 75-80% at the highest concentration of chlorophyllin studied. Control and reconstruction experiments showed that chlorophyllin was not toxic to Salmonella at the concentrations used. The antimutagenic activity of chlorophyllin was heat-stable. The mechanism of the antimutagenicity of chlorophyllin in these experiments is not known; however, chlorophyllin is an antioxidant. Scavenging of radicals and/or interaction with the active group of mutagenic compounds may be responsible for its antimutagenic activity. The data reported here indicate that chlorophyllin is potentially useful as an antimutagenic agent.

Chlorophyll↗

PubMed1986

Validation of the SOS/Umu test with mutagenic complex mixtures.

The SOS/Umu test, a rapid system for detecting genotoxic agents by monitoring SOS responses, was evaluated with the extracts of 8 mutagenic complex mixtures (airborne particles, coal dust, tobacco snuff, fried beef, fried shredded pork, airborne particles from polyurethane plants). In this system, the SOS function induced by genotoxicants is detected by a colorimetric measurement of beta-galactosidase in tester cells carrying a umuC-lacZ-fused gene on the plasmid. Results from the study show that a higher beta-galactosidase activity was found when the enzyme substrate and treated cells were added simultaneously into the enzyme reaction mixture and post-treatment dilution (10 X dilution with fresh medium) and incubation (for 2 h) were incorporated. The post-treatment dilution is necessary to reduce a possible false positive due to the color of test substances. The extracts of all mutagenic complex mixtures tested were found to induce dose-related SOS responses, indicating that the SOS/Umu test is potentially useful for the detection of mutagenic complex environmental mixtures.

Air Pollutants↗

PubMed1985

Dietary factors affecting the urinary mutagenicity assay system. I. Detection of mutagenic activity in human urine following a fried beef meal.

Studies have been conducted to determine whether the mutagens in fried beef ingested by human subjects are excreted in the urine. Urine samples were collected from individuals on liquid or regular diets before and after a fried beef meal. The mutagenic activity of the samples was tested in the Ames Salmonella/microsome assay system. The results showed that in individuals on liquid diets, most of the urinary mutagenic activity is recovered within 2-6 h after consuming a fried beef meal. In one individual tested, mutagenic activity was found in urine samples obtained 6-15 h after the fried beef meal. No mutagenic activity was detected in any of the urine samples obtained 15-24 h following the meal. In individuals on a regular diet, however, mutagenic activity was frequently observed in urine samples obtained 16-24 h following the fried beef meal, although the mutagenic activity was not as great as that in the preceding 16 h. It appears that the mutagenic agents generated by the frying of beef are ingested, absorbed, and excreted by the human body in biologically detectable quantities. These results suggest that subjects should abstain from fried beef at least one day prior to and during urine mutagenicity screening.

Animals↗

PubMed1985

The urine mutagenicity assay system. Studies related to recovery, storage and concentration procedures.

Studies were conducted to determine (i) the effect of storage on the mutagenic activity of urine spiked with known mutagens, (ii) the efficiency of XAD-2 column on the recovery of complex mixtures from spiked urine samples, and (iii) whether the addition of XAD-7 resin to the column and/or the addition of methylene chloride to the elution process increases the recovery of mutagens from urine samples spiked with complex mixtures. Chemically spiked or nonspiked urine samples were concentrated with XAD resin and were tested for mutagenic activity with the Ames Salmonella/microsome assay system. The results indicate that the mutagenic activity of chemically spiked urine remains essentially unchanged after 7 d, but it decreases by approximately 50% for some compounds after 28 d of storage at -70 degrees C. The recovery of mutagens from mutagen-spiked urine varied from 0% to more than 100%. Mutagenic activities of concentrates from urine samples spiked with complex mixtures were higher if resin columns were eluted with both methylene chloride and acetone than with acetone alone. A slight increase in mutagenic activity was also found if a mixture of XAD-2 and XAD-7 instead of XAD-2 alone was used to concentrate urine spiked with air particle extracts.

Chromatography↗

PubMed1984

Mutation tests in Neurospora crassa. A report of the U.S. Environmental Protection Agency Gene-Tox Program.

Many mutation tests have been developed in Neurospora crassa during the almost 40 years of its use in mutation research. These tests detect two major classes of mutation: gene mutation and meiotic nondisjunction. Within the first class, forward- and reverse-mutation tests have been used. The forward-mutation tests include those that detect mutations at many loci and at specific loci. Both kinds of forward-mutation tests have been done in homokaryons (n) and heterokaryons (n + n'). From the publications that were not rejected by our pre-established criteria, data were extracted for 166 chemicals that had been tested for mutagenicity. Only 6 of the 166 chemicals have been tested in one or more gene mutation test and the meiotic nondisjunction test; these 6 chemicals were positive in the first and negative in the second. Of the 102 chemicals tested in one or more gene mutation tests, 94 were positive and 8 were negative. Of the 70 chemicals tested in the meiotic nondisjunction test, 7 were positive and 63 were negative. Two tests, the ad-3 forward-mutation test and the meiotic nondisjunction test, have been used most frequently. These two tests are especially important for hazard evaluation, because each detects a class of mutations that is likely to be deleterious or lethal in the F1 - disomics by the meiotic nondisjunction test and multilocus deletions by the ad-3 forward-mutation test in heterokaryons. Generally, direct-acting chemicals are mutagenic in the gene mutation tests, but few chemicals that required metabolic activation have been tested. Only 31 of the 166 chemicals tested in N. crassa have been tested for carcinogenicity. Among these chemicals, there is a good association between mutagenicity in gene mutation tests and carcinogenicity but a poorer association between meiotic nondisjunction and carcinogenicity; however, only a small number of chemicals has been tested in the meiotic nondisjunction test. Further use and development of certain mutation tests in N. crassa are desirable.

Alleles↗

PubMed1984

Mutagenicity of tobacco snuff: possible health implications for coal miners.

Mutagenicity of tobacco snuff extracts was studied using the Ames Salmonella/microsome assay system. No mutagenic activity was found for tobacco snuff extracts without S9 activation. However, mutagenic substances were formed from tobacco snuff extracts in an acidic environment. The mutagenic substances induced predominantly frameshift mutations and were direct-acting mutagens. Mutagenic activity of tobacco snuff extracts was enhanced in the presence of coal-dust extracts at low pH. Since tobacco snuff has been used by some coal miners to substitute for cigarettes, a possible risk for gastric cancer induction among coal miners is proposed.

Animals↗

PubMed1983

Role of nitrosation in the mutagenic activity of coal dust: a postulation for gastric carcinogenesis in coal miners.

The mutagenicity of coal dust solvent extracts with and without nitrosation was studied using the Salmonella/microsome assay system. Coal dust solvent extracts were either non-mutagenic or very weakly mutagenic with S9 activation. High mutagenic activities, however, were found when extracts of bituminous, subbituminous, and lignite coal dusts were reacted with nitrite under an acidic condition. Formation of mutagens from coal dust extracts by nitrosation was highest at pH 3.2 and decreased with increasing pH in the reaction mixture. Mutagenic activity appeared to be independent of metabolic activation. The mutagens formed from nitrosation of coal dust extracts induced frameshift mutations. The results reported here may have possible implications for the explanation of an elevated incidence of gastric cancer in coal miners.

Coal↗

PubMed1983

Gastric cancer in coal miners: an hypothesis of coal mine dust causation.

An hypothesis is proposed to explain the elevated incidence of gastric cancer among coal miners. Inhaled coal mine dust, especially the larger particles, is cleared from the lung and tracheobronchial tree by mucociliary function, swallowed, and introduced into the stomach. Organic and/or inorganic materials in the dust can undergo intra-gastric nitrosation and/or interaction with exogenous chemicals to form carcinogenic compounds which in turn may lead to precancerous lesions, which may subsequently develop into gastric cancer. This sequence of events, however, depends upon occupational exposures as well as life-style features and individual genetic predisposition.

Coal↗

PubMed1983

Inhalation studies of diesel exhaust and coal dust in rats.

The preliminary 12-month data of an ongoing two-year chronic inhalation study into the effects of diesel exhaust and coat dust on rats are reported. The study design consists of four exposure regimens: coal dust, diesel exhaust, coal dust plus diesel exhaust, and filtered air (control). Total respirable particulate is being maintained at 2 mg/m3 in all exposure groups. Animals are being serially sacrificed and subjected to immunologic, biochemical, physiological, microbiological, and pathological evaluations. Extracts of diesel emissions showed marked mutagenic activities in the Ames Salmonella his reversion assay. Mutagenic compounds were not however found in the urine of the exposed animals, nor were sister chromatid exchanges detected in peripheral lymphocytes. No changes were observed in cytochrome P450 enzyme activity in lung microsomes of exposed rats. Physiological tests showed no evidence of pulmonary function impairment in any group. Light microscopic examination of the lungs showed dust deposition with the formation of macules in all exposed groups. The preliminary results revealed few pathological effects of significance and no evidence of synergism between diesel exhaust and coal dust.

Animals↗

PubMed1982

Studies of the mutagenic response of Salmonella typhimurium TA98 to size-fractionated air particles: comparison of the fluctuation and plate incorporation tests.

The high-volume Andersen sampler was used to study the mutagenic activity of size-fractionated airborne particles from ambient air in Morgantown, West Virginia. Mutagenicity was studied by the Ames Salmonella assay and the bacterial fluctuation test and was dependent on particle size in both systems, ie, the greatest activity was associated with the smallest particles. Comparison of the two systems was based on identical aliquots of each extract, cells prepared under identical conditions at the same time, and on mutagenic response at a predetermined level of statistical significance (P less than 0.05). The results suggest a slight advantage in sensitivity for the Ames test for the air samples under study.

Air↗

PubMed1981

Comparison of mutagenic and recombinogenic effects of some adenine analogues in Saccharomyces cerevisiae D7.

2-Aminopurine, 2-amino-N6-hydroxyadenine and N6-hydroxyaminopurine were compared in suspension test with growing and non-growing cells for their mutagenic and recombinogenic (reciprocal and nonreciprocal) activities in Saccharomyces cerevisiae strain D7. Ethyl methanesulfonate was used as a positive control. No increases above spontaneous frequencies were observed when non-growing cells were treated with the base analogues although EMS induced concentration-dependent responses at all 3 genetic end-points. When growing cells were treated, HAP was recombinogenic and mutagenic and AHA was mutagenic, but only weakly recombinogenic. HAP induced comparable numbers of revertants at much lower concentrations than AHA. 2AP failed to induce any detectable response even at concentrations as high as 2400 microgram/ml.

2-Aminopurine↗