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T Ong

Publications and source records attributed to T Ong.

At least 91 records · Page 5Linked to original sources

Inhibition of cyclophosphamide and mitomycin C-induced sister chromatid exchanges in mice by vitamin C.

Ascorbic acid (vitamin C) is known to act as an antimutagen and anticarcinogen in several test systems. However, there is no report of its effect on carcinogen-induced chromosomal damage in vivo in animals. The present study was performed to determine whether or not ascorbic acid affects sister chromatid exchanges (SCEs) induced by cyclophosphamide (CPA) and mitomycin C (MMC) in bone marrow and spleen cells in mice. The results indicate that ascorbic acid per se did not cause a significant increase in SCEs in mice. However, increasing concentrations of ascorbic acid caused decreasing levels of CPA- and MMC-induced SCEs in both cell types in vivo. At the highest concentration of ascorbic acid, 6.68 g/kg, approximately 75 and 40% SCE inhibition in both cell types was noted for CPA and MMC, respectively. Likewise, under in vivo/in vitro conditions (exposure of animals to experimental chemicals followed by culturing of cells), ascorbic acid caused a dose-related decrease in CPA- and MMC-induced SCEs, up to a dose of 3.34 g/kg At this concentration, approximately 50% CPA- and MMC-induced SCE inhibition was observed in both cell types studied. Thus, ascorbic acid acts as an anti-SCE agent in both in vivo and in vivo/in vitro conditions in mice.

Animals↗

Induction of sister chromatid exchanges by coal dust and tobacco snuff extracts in human peripheral lymphocytes.

The organic solvent extracts of sub-bituminous coal dust and tobacco snuff, both together and separately, were tested for the induction of sister chromatid exchanges (SCEs) in human peripheral lymphocytes. The results indicate that these extracts induced SCEs, and that when tested together synergistically induced SCEs in two of three donors. Studies with the organic solvent extracts of all five ranks of coal indicate that the extracts of bituminous, lignite, and peat, but not anthracite, induced SCEs. Similar experiments conducted with water extracts show that bituminous, lignite, and peat, but not sub-bituminous extracts, induced SCEs, and that anthracite was equivocal. To determine whether individuals differed in their SCE responses to coal dust extracts, lymphocytes from five donors were tested with organic solvent extracts of bituminous and sub-bituminous coal. An analysis of variance indicates that the SCE response was significantly influenced by the donor (p less than 0.0001) and each of the two coal extracts (p less than 0.0001). From studies of workers occupationally exposed to coal dust, it is known that inhaled coal dust is cleared from the lungs by mucociliary action and introduced into the stomach by swallowing. Coal dust, or coal dust plus snuff, may be responsible for the increased frequency of gastric cancer observed in coal miners. The findings presented here suggest that coal dust, with or without tobacco snuff, may play a role in the elevated incidence of gastric cancer in coal miners. Because water extracts of some ranks of coal induced SCEs, there exists the possibility of adverse environmental effects due to coal leachates.

Coal↗

Genotoxicity studies of rodents exposed to coal dust and diesel emission particulates.

Genotoxicity studies with mice and/or rats have been conducted to evaluate the potential mutagenic hazard associated with exposures of coal miners to diesel emission particulates (DEP) and/or coal dusts (CD). Rats and mice were exposed to filtered air, DEP, and/or CD for periods ranging from 3 months to 2 years. Levels of respirable particulates were maintained at 2 mg/m3 in all exposed groups. DEP and/or CD were collected in the inhalation chambers in which animals were exposed. Urine samples were collected for 5 consecutive days from rats exposed to DEP and/or CD for 3, 6, and 24 months. The particulate samples extracted with dichloromethane and the urine samples concentrated with XAD-2 columns were analyzed for mutagenic activity by the Ames Salmonella/microsome assay system. Peripheral blood lymphocytes from rats exposed for 3 months were analyzed for sister chromatid exchanges (SCE). The femur bone marrow cells from rats exposed for 24 months and mice exposed for 6 months were analyzed for micronuclei in both polychromatic and normochromatic erythrocytes. The results indicate that the solvent extract of DEP was mutagenic, while no mutagenic activity was found for the CD extract. Combination of CD and DEP did not show any synergistic effect. No mutagenic activity was found for urine samples from rats exposed to DEP and/or CD for up to 2 years. A slight increase in the micronucleated polychromatic erythrocytes over the control level was found in mice exposed to DEP and DEP plus CD for 6 months but the increase was not statistically significant. No increase in micronuclei was detected in rats exposed for 24 months. The frequencies of SCE in the peripheral lymphocytes of the 3-month-exposed rats were similar for control and DEP plus CD-exposed groups.

Animals↗

Dietary factors affecting the urinary mutagenicity assay system. II. The absence of mutagenic activity in human urine following consumption of red wine or grape juice.

The mutagenic activity of urine samples from nonsmoking individuals before and after the consumption of either red wine or grape juice was determined. Urine samples collected from individuals on liquid or regular diets were concentrated using XAD-2 resin. No mutagenic activity of urine concentrates was detected with Salmonella tester strains TA98 or TA100 with or without microsomal activation. The addition of 1000 units of beta-glucuronidase into the agar overlay did not show any mutagenic activity. The mutagens in red wine and grape juice, however, were extracted using the XAD-2 column. Concentrates of urine samples spiked with either of the two extracts exhibited mutagenic activity.

Diet↗

Formation of bacterial mutagens from the reaction of chewing tobacco with nitrite.

Using the Salmonella/microsome assay system, the mutagenicity of chewing tobacco extracts (CTE) treated with and without sodium nitrite under acidic conditions was examined. Mutagenic activity was found only for nitrite-treated CTE in both tester strains, TA98 and TA100, and was independent of metabolic activation. Formation of mutagenic substances from CTE by nitrite was dependent on acidic pHs (the highest at pH 2) and could be inhibited by ascorbate. The mutagenic potency of CTE plus nitrite was proportional to the content of nitroso compounds generated in the reaction mixture, indicating that the nitrosation process was involved. The possible in vivo nitrosation and the potential health effect are discussed.

Animals↗

Correlative genotoxicity studies of airborne particles in Salmonella typhimurium and cultured human lymphocytes.

The acetone extracts of ambient air particulates collected locally were tested for their capacity to induce sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) in human lymphocytes, and to induce gene mutations (GMs) in Salmonella typhimurium. The extracts caused dose-related clastogenic/mutagenic responses in all three assay systems. With the same concentration, it seems that the Ames Salmonella/microsomal assay with TA98 gave the highest, and the chromosomal aberration assay with human lymphocytes the lowest, mutagenic/clastogenic responses, respectively. Because high frequencies of SCEs were induced by solvent extracts of airborne particles, this study further indicated the usefulness of SCE assay in human lymphocytes for genotoxicity studies of airborne particles.

Air Pollutants↗

Genotoxic activity of nitrosated coal dust extract in mammalian systems.

The genotoxicity of coal dust extract nitrosated by NaNO2 was investigated because of an elevated incidence of gastric cancer in coal miners. Human peripheral lymphocytes were used to determine the frequency of sister chromatic exchanges (SCE) and chromosome aberrations. Chinese Hamster Ovary (CHO) cells were also used to measure SCEs. The mouse lymphoma forward mutation assay comprised the final in vitro system, while the micronucleus test on mouse bone marrow cells was used as an in vivo assay. The SCE frequency in human lymphocytes increased from 9.2 per cell in untreated cultures to 31.6 per cell in cultures treated with 10.0 microliter/ml of nitrosated coal dust extract (NCDE) (P less than .0001). Chromosome aberrations were tested during two phases of the cell cycle; the results indicate that NCDE causes an increase in aberrations in each cell phase tested. The SCE frequency in the CHO system increased from 9.0 per cell in untreated cultures to 18.0 per cell in cultures treated with 3.3 microliter NCDE per ml of medium (P less than .001). In the mouse lymphoma system, the background mutation frequency was tripled at 2.0 microliter NCDE per ml of medium. NCDE was not found to be active in the murine micronucleus assay. No consistent increase in genetic activity was observed with nonnitrosated coal dust extract alone or with NaNO2 alone. Metabolic activation greatly reduced or eliminated genetic activity. These results indicate that nitrosated coal dust extract is genetically active in in vitro mammalian systems without metabolic activation. These findings suggest that the nitrosation of ingested coal dust may be responsible for the elevated incidence of gastric cancer in coal miners.

Animals↗

Development of an in situ microbial mutagenicity test system for airborne workplace mutagens: laboratory evaluation.

A simple on-site Salmonella mutagenicity test system for the detection of airborne mutagens in the workplace is being developed. The system permits entrapment of mutagenic airborne particles and vapors by impinging unfiltered ambient air into trapping medium containing bacterial tester cells. The trapping device consists mainly of a pump, an impinger and a cyclone. The impinging air flow generated by the pump is approximately 3 1/min. New Salmonella typhimurium testers which are resistant to streptomycin (Str) and 8-azaguanine (AG) were derived from the Ames testers TA98 and TA100 and the arabinose-resistant tester SV50, and were used as mutation indicators. Microbial contamination was sufficiently controlled by addition of ampicillin, Str, AG, and cycloheximide to the trapping and plating media. New tester strains retained a high mutagenic sensitivity from their parent strains. Laboratory studies with volatile mutagens (methyl methanesulfonate, ethyl methanesulfonate, and dimethylnitrosamine) showed that the vapor trapping of this system is promising. The study with suspended silica particles coated with a known mutagen (2,4,7-trinitro-9-fluorenone) indicated that the particle trapping of the system is satisfactory. Incorporation of metabolic activation into the trapping medium by confining S9 mix and tester cells in dialysis tubing enabled this system to detect promutagens. This in situ system may be useful for mutagenic monitoring in the workplace.

Air Pollutants, Occupational↗

Validation of the Salmonella (SV50)/arabinose-resistant forward mutation assay system with 26 compounds.

Mutagenic sensitivity of the Salmonella/arabinose-resistant (Arar) assay system using the tester strain SV50 was evaluated with 26 compounds both by the preincubation and the standard plate incorporation tests. The mutagenic activity of all 26 compounds was also tested with TA98 and/or TA100 of the Ames Salmonella/microsome assay system. The results indicate that 13 and 10 of 26 compounds were mutagenic and nonmutagenic, respectively, in both assay systems. PR toxin and hydrogen peroxide were mutagenic only in the Arar assay, while 2-nitrofluorene was mutagenic only in the Ames assay. The results also show that the mutagenic response of SV50 to 13 of 15 mutagenic compounds was much higher (2.1-154-fold) if the compounds were tested with the preincubation rather than the plate incorporation test. The mutagenic activity of 4 compounds (diethyl sulfate, niridazole, PR toxin and hydrogen peroxide) in the Arar assay was detected only with the preincubation test. Since the Arar assay using tester strain SV50 has similar mutagenic sensitivity as the Ames assay to chemicals with different modes of action and since it requires only one tester strain, we find this assay system to be useful for screening environmental mutagens. Based on the effectiveness of the preincubation test in this study, it is recommended that the preincubation test instead of the plate incorporation test be used for the Arar assay system with tester strain SV50.

Arabinose↗

Detection of sister-chromatid exchanges in human peripheral lymphocytes induced by ethylene dibromide vapor.

A method using sister-chromatid exchanges (SCEs) for genotoxic testing of gaseous compounds is described. Human peripheral lymphocyte cultures previously stimulated with phytohemagglutinin were placed in sterile dialysis tubing and then put in an enclosed flask containing additional culture media. Air, with or without ethylene dibromide (EDB), was bubbled through the flask for up to 8 h. The cultures were harvested 75 h after culture initiation, and second-division cells were scored for induction of SCEs according to established procedures. The SCE frequency was approximately doubled in cultures treated with EDB. A similar experiment with air alone resulted in only slight increases in SCEs. The results indicate that this system is potentially useful for detecting genotoxicity of gases and vapors and may be useful for the detection of genotoxic agents in occupational settings.

Cells, Cultured↗

Genotoxic properties of 2,4,7-trinitro-9-fluorenone.

The genotoxic effects of 2,4,7-trinitro-9-fluorenone (TNF) were studied in assays employing procaryotic (Salmonella typhimurium and Escherichia coli) and eucaryotic (Saccharomyces cerevisiae, mouse lymphoma L5178Y and Chinese hamster ovary) cells. The results show that TNF is a potent mutagen for procaryotes. It causes both frame-shift and base-pair substitution mutations, although frame-shift mutations were predominant. In Saccharomyces cerevisiae, this compound appeared to be too toxic to permit detection of genotoxic effects. TNF was also toxic to mouse lymphoma cells and Chinese hamster ovary cells but the toxic effects were reduced by metabolic activation. TNF induced a clear increase in sister-chromatid exchanges in CHO cells and in mutant frequency in mouse lymphoma cells both in the presence and absence of metabolic activation.

Animals↗

Mutagenicity studies of ambient airborne particles. I. Comparison of solvent systems.

Organic materials were extracted from airborne particles by shaking with different solvent systems including acetone, benzene, cyclohexane, dichloromethane (DCM), methanol, a mixture of acetone and DCM and a combination of benzene, cyclohexane and methanol. The solvent-extracted materials were tested for mutagenic activity with the Ames Salmonella/microsomal assay system. Acetone- and cyclohexane-extracted materials gave the highest and lowest mutagenic activities, respectively. Re-extraction experiments confirmed that most of the mutagenic material from air particles cannot be extracted by cyclohexane. The sequential extraction with acetone followed by DCM gave a better mutagenic response than acetone alone or acetone in combination with DCM. Extraction with varying amounts of solvent indicated that 1 ml of acetone per mg of airborne particles reached the maximum recovery of mutagenic material.

Air Pollutants↗

Mutagenicity studies of ambient airborne particles. II. Comparison of extraction methods.

Organic materials were extracted with acetone from airborne particles by shaking, soxhletion and sonication for varying durations. 4-h, 1-h and 1/8-min extractions by shaking, soxhletion and sonication, respectively gave maximum his+ revertants with the Ames Salmonella/microsome assay. In a comparative study of extraction methods, sonication gave the highest and soxhletion the lowest mutagenic response. It appears that sonication with acetone is the best procedure for the extraction of mutagens from airborne particles as shown by Ames assay and Arar assay systems in Salmonella typhimurium.

Air Pollutants↗

Comparison of the cytotoxic and mutagenic effects of selected mutagens on excision repair-sufficient and -deficient AD-3 mutants of Neurospora crassa.

The excision repair-deficient genetic marker uvs-2 was crossed into the tester strains N23 and N24 of Neurospora crassa. Comparison was made among the effects of selected mutagens on a repair-sufficient strain (N23 or N24) and a repair-deficient strain (N23 uvs-2 or N24 uvs-2) with regard to cell killing and induction of reverse mutation from adenine dependence to adenine independence. Methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), 1,2,7,8-diepoxyoctane (DEO), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 2,3,5,6-tetraethyleneimino-1,4-benzoquinone (TEB) and ICR-170 were found to be more toxic to the repair-deficient strains than to the repair-sufficient strains. For the induction of reverse mutations N23 uvs-2 appeared to be more sensitive than N23 to MNNG and TEB and to the high concentrations of MMS and DEO while N24 was 20 times more sensitive than N24 uvs-2 to ICR-170.

Crosses, Genetic↗

Mutagenic detection of complex environmental mixtures using the Salmonella/arabinose-resistant assay system.

The mutagenic sensitivity of SV50, the R-factor plasmid containing tester, of the Salmonella/arabinose-resistant assay system has been evaluated with different environmental complex mixtures, including extracts of airborne and diesel emission particles, oil-shale ash, nitrosated coal dust and water samples. The mutagenicities of all extracts were detectable with this assay. This study indicates that the arabinose-resistant assay with SV50 is useful for the detection of the mutagenic activity of environmental complex mixtures.

Air Pollutants↗

Mutagenicity of oil-shale ash.

3 oil-shale ash samples were extracted with solvents and analyzed for mutagenicity with a number of tests systems. In Salmonella typhimurium, the ash extracts were highly mutagenic with the Ames his reversion and the ara-resistant systems. Mutation induction by the ash in Salmonella was independent of metabolic activation and was of the frameshift type. These ash extracts showed a substantial killing effect, but failed to induced ad-3 reversion in Neurospora crassa, gene conversion and mitotic crossing-over in Saccharomyces cerevisiae and TGr mutation in cultured CHO cells.

Animals↗