Search PubMed⌕ Search

Biomedical subjects

J Meyne

Publications and source records attributed to J Meyne.

50 records · Page 3Linked to original sources

Hepatotoxic doses of dioxin do not damage mouse bone marrow chromosomes.

We report on a study of the cytogenetic and hepatotoxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mice of the C57B1/6J (with high-affinity TCDD receptor) or DBA/2J (with low-affinity TCDD receptor) strains were given single intraperitoneal injections of 50, 100 or 150 micrograms of TCDD/kg body weight. At various times (8-48 h) after injection, we examined bone marrow cells for cytogenetic effects by performing structural aberration, sister-chromatid exchange, and micronucleus tests. 1 month after exposure, liver sections were studied for hepatotoxic effects. We found no evidence of chromosome damage by TCDD given in doses that cause liver damage in both strains of mice.

Animals↗

Counterstaining human chromosomes for flow karyology.

Isolated human metaphase chromosomes stained with the fluorochromes 4'-6-diamidino-2-phenylindole (DAPI) and chromomycin A3(CA3), and counterstained with nonfluorescent netropsin (NTR), have been analyzed by dual-laser flow cytometry. Counterstaining with NTR reduces DAPI fluorescence except at regions on chromosomes 1,9,15,16, and Y, corresponding to C-band heterochromatin. Bivariate flow karyology of human chromosomes treated with this triple-stain combination resolves chromosomes 1,9, and Y distinctly from the remaining chromosomes and resolves variations between chromosome homologues not detected by staining with propidium iodide (PI) or with the double stain combination Hoechst 33258(HO) and CA3.

Cells, Cultured↗

Computerized measurement of the DNA content, areas, and autoradiographic grains of the same nuclei: demonstration that lightly (3H)thymidine-labeled bone marrow cells are predominantly in G0/G1 and G2.

A computerized "flying spot" microdensitometer and scanning stage have been combined to measure the cellular DNA content, nuclear areas, and autoradiographic grain areas of the same cells. The slide positions of the Feulgen-stained, (3H)thymidine-labeled cells are mapped with the computerized stage, and nuclear DNA content and areas are then determined by integral absorbance measurements at 588 nm. Following autoradiograph preparation, the cells are relocated and the areas of the autoradiographic grains over each nucleus are measured at a light wavelength (625 nm) and an optical density setting (greater than 0.10) that do not detect the Feulgen stain. The microcomputer calculates the portion of each nucleus covered with autoradiographic grains (grain area proportion, GAP), and it links the GAP value to the DNA content of each nucleus in the computer file for subsequent sorting and analysis. By using this system in a study of mouse bone marrow cells labeled in vivo with (3H)thymidine, we found that all S-phase cells were clearly labeled after 8 or more days of autoradiographic exposure. Prolonged exposures (up to 64 days) led to detection of lightly labeled cells (0.1 less than GAP less than 0.8) with G1/G0 and G2 DNA content.

Animals↗

Clastogenic effects of transplacental exposure of mouse embryos to nitrogen mustard or cyclophosphamide.

Embryos from day 12 pregnant Swiss mice given intraperitoneal injections of nitrogen mustard (HN2) or cyclophosphamide (CP) were evaluated for chromosomal aberrations. Both agents induced dose-dependent increases in the frequency of cells with aberrations observed in embryos from females treated 6 hr before sacrifice. The highest frequencies of cells with aberrations were observed when females were injected 15 or 18 hr before sacrifice on day 12. A teratogenic dose of HN2 (1.0 mg/kg) induced significantly higher frequencies of damaged cells than a teratogenic dose of CP (20 mg/kg). Cytogenetic analysis of rodent embryos from pregnant females exposed to xenobiotic agents may be an effective screening test for evaluation of genetic effects induced by transplacental exposure.

Animals↗

Cytogenetic effects of shale-derived oils in murine bone marrow.

The cytogenetic effects of exposure of mice to shale-derived oils by either skin painting or intraperitoneal injection were examined. Skin painting with 40 mg crude oil every other day for five weeks had no effect on the frequency of chromosomal aberrations observed in the bone marrow. Three daily intraperitoneal injections of 0.5-2.0 ml/kg per day of a crude shale oil from an aboveground retort induced a dose-related increase in the frequency of aberrations observed. A hydrotreated sample of this oil produced a similar pattern of aberration induction, but at lower frequencies. Crude shale oil from a modified in situ retort induced the highest frequency of chromosomal aberrations at the 0.5 ml/kg dose; lower frequencies were induced at the 1.0 ml and 2.0 ml/kg doses. Of the three shale oils tested, only the crude oil from the aboveground retort induced increased frequencies of sister chromatid exchanges and only at doses that also induced structural aberrations. These studies indicate that structural aberration analysis is a more sensitive test than sister chromatid exchange analysis for the type of DNA damage induced by shale-derived oils in murine bone marrow cells.

Animals↗

In vivo cytogenetic effects of oil shale retort process waters.

The induction of cytogenetic effects by oil shale retort process waters from 3 types of pilot plant retorts were examined in murine bone marrow. Each of the process waters induced increased frequencies of structural aberrations in mice treated with 3 daily intraperitoneal injections of the waters. The same treatment had no effect on the frequency of sister chromatid exchanges. Mice given a 1% solution of an above-ground retort water ad libitum for 8 weeks consumed about 1 ml/kg per day of the process water and had a frequency of aberrations comparable to mice given the same dose intraperitoneally for 3 days. Transplacental exposure of C3H mouse embryos indicated that clastogenic compounds in the above-ground retort process water can cross the placenta and induce chromosomal aberrations in embryonic tissues.

Animals↗

Sex-related differences in cytogenetic effects of benzene in the bone marrow of Swiss mice.

Two routes of administration-intraperitoneal injection and oral gavage-and two methods of analysis-direct metaphase preparations and the micronucleus test-were used to investigate the cytogenetic effects of benzene exposure in the bone marrow of female and male Swiss (CD-1) mice. The males demonstrated higher mean frequencies of metaphase aberrations and micronuclei after both routes of administration. The frequencies of metaphase aberrations appeared to be sex-related and independent of the route of exposure, however, while the frequencies of micronuclei appeared to be dependent upon both the sex of the animals and the route of administration.

Animals↗

The evaluation of the epoxide diluent, n-butylglycidyl ether, in a series of mutagenicity assays.

The epoxide diluent, n-butylglycidyl ether (n-BGE), was tested in vitro for mutagenicity using Salmonella typhimurium and for transforming ability in mouse embryo cells (BAlb/3T3-A31-1-13). The n-BGE produced base-pair type mutations in S typhimurium strains TA1535 and TA100. However, it failed to transform mouse embryo cells when assayed up to toxic levels. The mutagenic activity could not be detected in the urine of mice, although several doses, routes of administrations, and lengths of exposure were examined. Orally administered n-BGE did not produce any increase in micronuclei in mice, but when the diluent was administered intraperitoneally, either one or two times, dose-related increases in the number of micronuclei were observed.

Animals↗

The mutagenic evaluation of tetrakis (hydroxymethyl) phosphonium sulfate using a combined testing protocol approach.

This study was undertaken to evaluate the mutagenicity of the flame retardant, Tetrakis (Hydroxymethyl) Phosphonium Sulfate -75% or its possible metabolic products using a battery of in vitro and in vivo assays. The starting material in the fabric treatment process, THPS was tested with five strains of Salmonella typhimurium with and without the addition of a rat liver activating system. In addition, the THPS and the treated fabric were assayed in a combined testing protocol. The mutagenicity tests which were employed in this protocol included (a) the analysis of the urine of treated mice, (b) the micronucleus test, and (c) metaphase analysis. The animals were administered the THPS both orally and dermally and the treated fabric was incorporated into the animals' feed. The THPS produced no mutagenic response in any of the strains of S. typhimurium either when tested directly or with the addition of Acroclor--or phenobarbital-- induced rat liver. The results of the combined testing protocol, with the three routes of administration, were also negative for the urine analysis, micronucleus test and metaphase analysis.

Administration, Oral↗

Nonrandom distribution of chromosomal aberrations induced by three chemicals.

The G-band locations of 3244 breakpoints induced by cis-platinum (II) diamminedichloride (PDD), 1460 breakpoints induced by cytosine arabinoside (ara-C), and 1257 breakpoints induced by triethylenemelamine (TEM) in human lymphocyte chromosomes were identified. The breakpoints induced by each of these chemicals demonstrated a significantly nonrandom distribution within the human karyotype. The overall pattern of the interarm distribution was dependent upon the chemical used, but certain chromosomes arms exhibited similar responses to all 3 chemicals. Comparison of the frequencies of breakpoints within individual G-bands indicated that (1) certain bands were susceptible to damage induced by all 3 chemicals; (2) certain bands were resistant to damage by all 3 chemicals; (3) certain bands demonstrated variable susceptibility to induced damage dependent upon the chemical agent; and (4) other bands demonstrated near expected frequencies of damage (by length) to all 3 agents.

Cells, Cultured↗

A combined testing protocol approach for mutagenicity testing.

The antischistosomal agent, hycanthone methanesulfonate (HMS), was employed to illustrate the utility of carrying out several mutagenicity tests in a single concurrent animal experiment. Several commonly used procedures that were successfully integrated into a multiple testing protocol included (1) metaphase analysis in bone marrow, (2) micronucleus test in bone marrow, (3) analysis of the urine for mutagenic constituents, and (4) the host-mediated assay using Salmonella typhimurium. In addition to these animal studies, in vitro mutagenicity testing with and without activation was carried out using S. typhimurium. HMS produced positive, dose--response effects in in vitro tests, metaphase analysis, micronucleus test, and urine analysis, but not in the host-mediated assay. The results of these integrated techniques suggest that such a protocol may be a benefit to those concerned with mutagenicity testing of chemicals.

Animals↗

Cytogenetic effects of cis-platinum(II)diamminedichloride on human lymphocyte cultures.

Human lymphocytes were treated with the antitumor agent cis-platinum)II)diamminedichloride (PDD) during either the last 24 h or 48 h of incubation. A dose-dependent effect was observed for both inhibition of mitotic activity and increased frequency of metaphases with chromosomal aberrations. The aberrations observed consisted primarily of chromatid breaks. Statistical analysis of 3244 PDD-induced breakpoints demonstrated a significantly nonrandom distribution of breakpoints between chromosomes. The pattern of distribution varied with the type of aberration. Only chromosome number 9 had a significant increase of breakpoints for each type of aberration analyzed. The breakpoints were located predominantly in lightly staining G-gands. Certain individual bands had relatively high frequencies of breakpoints, indicating a specific interaciton occurs between PDD and the DNA of human lymphocytes in vitro.

Cells, Cultured↗