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Biomedical subjects

R van Doorn

Publications and source records attributed to R van Doorn.

33 records · Page 2Linked to original sources
PubMed1981

Metabolic activation of 2-aminofluorene by isolated rat liver cells through different pathways leading to hepatocellular DNA-repair and bacterial mutagenesis.

The aromatic amine 2-aminofluorene (2-AF) is metabolised by isolated rat liver cells to reactive species, thereby causing mutagenic effects in Salmonella typhimurium TA 1538 and evoking DNA-excision repair within the liver cells. The pathway leading to the production of metabolites mutagenic in Salmonella is likely to proceed via direct N-hydroxylation of 2-AF to N-hydroxy-2-aminofluorene (N-OH-2-AF). On the other hand, the formation of intermediates giving rise to hepatocellular DNA-repair is shown to depend upon N-acetylation of 2-AF to 2-acetylaminofluorene(2-AAF), whereas a subsequent conjugation reaction, most likely to be sulfate ester formation, is also essentially involved.

2-Acetylaminofluorene↗
PubMed1981

Involvement of non-oxidative enzymes in mutagenic activation of urine from rats, given benzidine and some other aromatic amines.

Urinary metabolites of rats treated with benzidine and some other genotoxic aromatic amines became mutagenic in the Ames assay after activation with liver cytosol from rat, mouse and guinea pig. Most of the mutagenic metabolites appeared in urine as glucuronides. Strong evidence was found that N,O-acyltransferase is responsible for the mutagenic activation by rat liver cytosol. The inhibitory effect of paraoxon and sodium fluoride indicates that the activation by mouse liver cytosol is due to the action of deacetylase. Mutagenic activation by guinea pig liver cytosol seemed to be mediated in part by deacetylase. The metabolite activated by these enzymes most likely is a glucuronidated, N-acetylated, N-hydroxylated product.

Amines↗
PubMed1981

Enhanced excretion of thioethers in urine of operators of chemical waste incinerators.

Thioether concentrations were determined in urine samples obtained from ten workers in the despatch department (n = 69), three chemical waste incinerator operators (n = 67), and an analyst (n = 21), all working in the same chemical plant. Urine samples (n = 196) obtained from non-exposed men, including smokers, served as controls. Enhanced excretion of thioethers was found in urine samples taken from incinerator workers at the end of work. A regular pattern in the time course of the urinary thioether excretion was shown by a non-smoking incinerator worker; end-of-work values were always higher than prework values. This phenomenon was not found in samples obtained from the analyst. These findings suggest that incinerator workers inhale or otherwise absorb electrophilic compounds or their precursors, which are subsequently metabolised to, and excreted as, thioethers in urine.

Chemical Industry↗
PubMed1981

Non-histone chromatin proteins in human thymocytes and T lymphocytes from blood.

The composition of nuclear proteins from human thymocytes and T lymphocytes from peripheral blood was analyzed. Total thymocytes and total peripheral blood T lymphocytes differed markedly in non-histone chromatin proteins (both phosphorylated and non-phosphorylated), but did not differ in histones. When the cells were separated according to density, T-lymphocyte fractions with a close specific gravity showed restricted differences in non-histone chromatin patterns.

Cell Count↗
PubMed1980

Effect of toluene and xylenes on liver glutathione and their urinary excretion as mercapturic acids in the rat.

Administration of toluene and xylenes to rats caused a decrease in liver glutathione concentration. The effect was most pronounced after the administration of o-xylene. 26% of the initial glutathione level was found three hours after treatment with o-xylene (4.0 mmoles/kg). No in vitro conjugation of o-xylene with glutathione was observed, neither spontaneously nor in the presence of 105,000 g supernatant from rat liver homogenate, containing glutathione S-transferases. Thus, a metabolite of o-xylene, which is not formed during incubation with 105,000 g supernatant, reacts with glutathione. A thioether was isolated from urine of rats given o-xylene; the compound was identified as o-methylbenzyl mercapturic acid by GC-MS and NMR. Chromatographic evidence was found for the presence of benzyl mercapturic acid in the urine of toluene-treated rats. The amounts of mercapturic acids excreted in the urine after administration of toluene, p-xylene, m-xylene, and o-xylene were 0.4-0.7,0.6,1.3, and 10-21% of the dose, respectively. These results demonstrate the involvement of a thusfar unknown pathway in the biotransformation of toluene and xylenes.

Acetylcysteine↗
PubMed1980

The appearance of mutagens in urine of rats after the administration of benzidine and some other aromatic amines.

The mutagenicity of urine from rats treated with benzidine or 5 other arylamines (0.25 mmol/kg; i.p.) was studied using the Ames-assay. It was found that samples of urine collected for 24 h after the administration of the carcinogens, benzidine, 4-aminobiphenyl and 2-aminonaphthalene, showed significantly mutagenic activity, whereas no mutagenicity was observed in urine after treatment with 3,3'-5,5'-tetramethylbenzidine, 2-aminobiphenyl and 1-aminonaphthalene. Mutagenic activities were dependent on the use of either hepatic S-9 Mix or cytosol as the activating enzyme preparation. The addition of beta-glucuronidase enhanced mutagenicity, except for 2-aminonaphthalene. The appearance of mutagens in urine was studied at varying doses of benzidine and at different time-intervals after the administration. The different excretion patterns found after the activation either with S-9 Mix or with cytosolic enzyme(s) suggest the presence in urine of different types of mutagenic products.

Amines↗
PubMed1978

Synergistic effects of phorone on the hepatotoxicity of bromobenzene and paracetamol in mice.

Administration of phorone (diisopropylidene acetone), an industrial solvent, to mice caused a rapid depletion of hepatic glutathione, which is due to enzymatic conjugation of phorone with glutathione, mediated by cytoplasmic enzymes of the liver. Whereas phorone, even in high doses, did not show hepatotoxic effects by itself, combined administration of phorone with a subtoxic dose of either paracetamol or bromobenzene strongly enhanced hepatotoxicity of the latter compounds as was judged from a rise in serum transaminase activities. These findings are compatible with the concept of a dose threshold for biologically reactive intermediate compounds which are bioinactivated through glutathione conjugation.

Acetaminophen↗
PubMed1976

A method for the recognition and separation of human blood monocytes on density gradients.

The density distribution of human mononuclear blood leukocytes was studied in order to define the optimal conditions for the separation of monocytes and lymphocytes by isopycnic centrifugation. Under standardized conditions, two populations of cells with partially overlapping, normally distributed densities were consistently found. The cells with the lowest density were recognized as monocytes, using phagocytosis and size distribution analysis as criteria. Since the density of monocytes continuously increased during the centrifugation, optimal separation of monocytes and lymphocytes could only be achieved by limiting the time of centrifugation to 10 min at 2200 g and 4 degrees C. The separation on discontinuous density gradients decreased when the load exceeded 8 X 10(6) mononuclear cells per sq cm. Analysis of the composition of the two cell populations obtained after separation on a three-layer discontinuous gradient revealed that the contamination of the monocytes with lymphocytes was due to the partial overlapping density distributions of both cell types. A small and a large scale method for isolation of monocytes from blood on discontinuous density gradients are presented. Under the described conditions, a preparation of functionally intact monocytes can be obtained which is comparable, both in yield and purity, to those obtained by methods based on surface adherence without the drawbacks of the latter methods.

Cell Separation↗
PubMed1976

Size distribution, electronic recognition, and counting of human blood monocytes.

During a study on the separation of human blood monocytes from lymphocytes, a method was developed to recognize and count monocytes by electronic means. Lightscattering (Cytograf, Bio/Physics), and changes in electrical resistance (Channelyzer, Coulter) were used to size mononuclear leukocytes directly in cell suspensions. Both methods revealed a size distribution profile in which two populations of mononuclear leukocytes could be distinguished. The largest cells were virtually eliminated after phagocytosis of iron particles. We confirmed that these cells were monocytes by three different criteria: the intracellular lysozyme activity, the number of phagocytes, and the percentage of cells with kidney-shaped nuclei. The highly significant correlations we found showed that monocytes could be recognized and counted by electronic sizing. For this method, purified mononuclear leukocyte preparations had to be used, since the presence of erythrocytes, platelets, and polymorphonuclear cells interfered. Statistical analysis revealed that electronic sizing permitted discrimination of differences in monocyte content of 4.5%, with a probability of 95%. It was calculated that this sensitivity of electronic monocyte counting was about three times higher than the sensitivity of microscopic methods. Since 100,000 cells can be sized within a few seconds, not only the efficiency of the preparation but also minor changes in the size of monocytes and lymphocytes introduced during the isolation can be followed.

Cell Separation↗
PubMedDate not supplied

Determination of thio compounds in urine of workers exposed to carbon disulfide.

Metabolites of carbon disulfide excreted into the urine of viscose workers are detectable by application of a nonselective assay for the determination of thio compounds. Enhanced secretion of thio compounds occurred especially at the end of the workday in exposed workers. A classification of urine samples according to the degree of exposure gave evidence for a relation between exposure to carbon disulfide and excretion of thio compounds in urine. The presence of 2-thiothiazolidine-4-carboxylic acid in urine of viscose workers was indicated by TLC, UV-spectrometry, and HPLC.

Air Pollutants↗