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Biomedical subjects

J Xu

Publications and source records attributed to J Xu.

At least 1,297 records · Page 72Linked to original sources

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↗

Comparative mutagenicity studies of azo dyes and their reduction products in Salmonella typhimurium.

The arabinose-resistant and Ames assay systems of Salmonella typhimurium were used to evaluate the mutagenic potential of azo dyes and their aromatic amine reduction products. Azo dyes, namely direct black 38, direct blue 15, and direct red 2, were mutagenic in the arabinose-resistant and Ames assays with both hamster and rat liver S9 activation. Both assays gave relatively higher mutagenic responses with hamster S9. Reduction products of these dyes, namely benzidine, o-dianisidine, and o-tolidine, were mutagenic in the Ames assay. Benzidine was weakly mutagenic and o-dianisidine and o-tolidine were nonmutagenic in the arabinose-resistant assay. These results indicate that both arabinose-resistant tester SV50 and Ames tester TA98 were sensitive in detecting mutagenicity of azo dyes. The use of the standard plate protocol with Ames tester TA98 is more efficient than the modified azo dye protocol in detecting mutagenicity of aromatic amine reduction products. Additional modifications in either the standard plate or modified azo dye protocols may improve detection of mutagenicity of these compounds in the arabinose-resistant assay system.

Animals↗

Gamma aminobutyric acid B receptor-mediated inhibition of adenylate cyclase in cultured cerebellar granule cells: blockade by islet-activating protein.

In primary cultures of cerebellar granule cells, the gamma aminobutyric acid B (GABAB) receptor couples to an inhibitory mechanism of adenylate cyclase. The inhibition of adenylate cyclase can be observed either by the measurement of cellular cyclic AMP content or by in vitro measurement of adenylate cyclase from plasma membrane of these cerebellar granule cells. The GABAB receptors can be stimulated by GABA and the GABA analog, baclofen. This receptor-mediated inhibition of adenylate cyclase was blocked by the pertussis toxin, islet-activating protein. Furthermore, the authors show that islet-activating protein catalyzed the ADP ribosylation of the guanine nucleotide inhibitory unit (MW 41,000) in the cerebellar granule cells. In summary, the authors provide evidence supporting the presence of a GABAB receptor in the cerebellar granule cells and suggest that this receptor couples with the guanine nucleotide inhibitory unit to inhibit the formation of cyclic AMP.

1-Methyl-3-isobutylxanthine↗

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↗

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↗

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↗

Comparative studies on spontaneous and mitomycin-C-induced sister-chromatid exchanges in smokers and non-smokers.

Both spontaneous and mitomycin-C-induced sister-chromatid exchanges were analyzed in 6 smokers and 6 non-smokers. The average number of spontaneous SCE in smokers' cells was 8.33 +/- 1.08. The frequency in the non-smoking controls was 4.41 +/- 0.72. This difference is highly significant (P less than 0.001). Smokers also had more SCE at all levels of mitomycin C testes. Analysis of variance showed these differences to be highly significant (P less than 0.001).

Cells, Cultured↗