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J Schöneich

Publications and source records attributed to J Schöneich.

14 recordsLinked to original sources

Detection of 6-thioguanine-resistant spleen lymphocytes in different mouse strains by autoradiography.

The variant frequencies for 6-thioguanine-resistant spleen cells in different mouse strains have been estimated by autoradiography for animals without chemical treatment and in cases of in vivo mutagen dosage with ethylnitrosourea and cyclophosphamide, respectively. In untreated mice, the following variant frequencies have been found: C57Bl/6J, 2.84 x 10(-5);NMRI, 3.04 x 10(-5);DBA/2J, 5.91 x 10(-5). The selective concentration of 6-thioguanine was 100 microM for strains NMRI and DBA, while in the case of C57Bl with this concentration, no variant cells could be counted and a selective concentration of 50 microM was chosen. Treatment with 70, 140, and 210 mg/kg ethylnitrosourea resulted in increased variant frequencies in cells isolated 8 or 15 days later. On the other hand, doses of 20, 60, and 120 mg/kg cyclophosphamide did not result in a clear dose-response relationship of variant frequency in cells isolated 1, 8, 15, 22, and 29 days after treatment. These data are discussed with respect to findings in human populations exposed occupationally to cyclophosphamide.

Animals

Cytogenetic monitoring of chemical workers in production of the drug 1-propoxy-2-acetamino-4-nitrobenzol with reference to their smoking habits.

The induction of chromosome aberrations (CAs) and sister-chromatid exchanges (SCEs) was examined in cultured lymphocytes from 23 individuals employed in the production of the drug 1-propoxy-2-acetamino-4-nitrobenzol. Lymphocytes of workers were cultured before and 13 weeks after starting professional activity. The latter showed a significant increase in both CAs and SCEs. Smokers (11 individuals) and non-smokers (12 individuals) were indistinguishable with respect to the frequencies of CAs or SCEs before starting professional activity, 13 weeks later smokers exhibited significantly more SCEs than non-smokers. This strongly suggests a comutagenic interaction of cigarette smoke and exposure to chemicals during drug production. On the basis of the technology applied the compound inducing CAs and SCEs in lymphocytes of smoking workers seems to be 2-acetamino-4-nitrophenol.

Acetanilides

Increased frequency of 6-thioguanine-resistant lymphocytes in peripheral blood of workers employed in cyclophosphamide production.

The frequency of 6-thioguanine-resistant peripheral blood lymphocytes has been determined by autoradiography in a control population and a population of cyclophosphamide-exposed individuals. The mean variant frequency in a non-exposed population was found to be 2.76 +/- 1.48 X 10(-5). Subpopulations of smokers and non-smokers revealed statistically significant differences in the variant frequencies, i.e. 3.52 +/- 1.55 X 10(-5) and 2.07 +/- 1.05 X 10(-5) respectively. In 20 out of a total of 23 individuals employed in cyclophosphamide synthesis and manufacturing, the variant frequency of 6-thioguanine-resistant lymphocytes was found to be higher than the maximum individual frequency found in the control population. The mean variant frequency in the cyclophosphamide-exposed population was 13.64 +/- 13.56 X 10(-5), a statistically significant increase as compared to the mean control frequency. There was no correlation between variant frequency and duration of employment suggesting that this test reflects the actual exposure and not a cumulative effect.

Adult

Specific effects of nerve growth factor on the differentiation pattern of mouse embryonic stem cells in vitro.

The effect of nerve growth factor (NGF) on the differentiation pattern of pluripotent undifferentiated mouse embryonic stem cells (ESC) was studied. Morphological analysis of differentiating stem cells and histochemical silver-staining analysis of embryonic carcinoma (P19S1801A1) and embryonic stem cells (ESC-BLC 6) permitted the demonstration of nerve cell differentiation. NGF treatment resulted in an accelerated appearance of neuron-like cells in differentiating embryoid bodies of ESC line BLC 6. By use of the silver-staining test NGF dependent induction of nerve cell lineage was demonstrated. The presented embryonic stem cell model allows to study the time course of differentiation and induction of a special cell lineage of undifferentiated embryonic stem cells by growth factors.

Animals

Immunochemical differentiation of glucose phosphate isomerase (GPI) allozymes of the mouse.

Polyclonal xenoantisera against mouse GPI-1B and GPI-1C were produced in rabbits and analyzed for their ability to recognize allozyme-specific determinants. These studies showed a high degree of serological similarity among the three allozymes of mouse glucose phosphate isomerase (GPI). However, GPI-1B and GPI-1C could be differentiated from GPI-1A as well as GPI-1A and GPI-1B from GPI-1C using quantitative solid-phase immunobinding assays. In addition, polyclonal and monoclonal alloantibodies specific for GPI-1C were produced in BALB/c (Gpi-1a/Gpi-1a) mice. As indicated by immunoblotting data, the allozyme specificity of rabbit antisera and monoclonal alloantibodies against GPI-1C is dependent on the native structure of that allozyme.

Animals

Transplacental genetic and cytogenetic effects of alkylating agents in the mouse. II. Induction of chromosomal aberrations.

Six monofunctional alkylating agents, trenimon, cyclophosphamide, and isoniazid were proven for transplacental cytogenetic activity in mouse embryos at day 10 of gestational age under the same conditions as used in the mammalian spot test. With the exception of isoniazid, all compounds led to an increase in the aberration frequencies in embryonal cells. The results were statistically not significant in the case of EMS, while all other chemicals showed a dose-dependent clastogenic activity. After treatment with monofunctional alkylants, chromatid breaks were dominating, while polyfunctional compounds also produced chromatid exchanges, especially in the case of trenimon. ENU and DMS showed a very early aberration maximum 6 hr after injection. For both compounds, very similar dose-response curves were found for induction of chromatid breaks in the dose range 10-75 mg/kg. There is no correlation between the Swain-Scott factors of monofunctional alkylants and their ability to induce chromosomal damage when compared in terms of pharmacological doses. A quantitative comparison of data found in the cytogenetic test in embryonal cells with those obtained in the mammalian spot test led to the conclusion that chromosomal mutations are of minor relevancy for the expression of recessive alleles in heterozygous mouse embryos. With this respect, the mammalian spot test must be considered as an in vivo test for the detection of gene mutations in somatic cells of the mouse.

Alkylating Agents

The effect of the mode of administration of nitrogen mustard and cytosine arabinoside on the production of chromosomal aberrations in mouse bone marrow and ascites tumour cells.

The cytogenetic effects of intraperitoneally (i.p.) and subcutaneously (s.c.) administered nitrogen mustard (HN2) and cytosine arabinoside (ara-C) on bone-marrow and ascites tumour cells of mice were studied. Ehrlich ascites tumour-bearing mice were treated with the mutagens, and cytological preparations were made from ascites tumour and bone-marrow cells of the same animal. The following parameters were investigated: frequencies of mitotic and chromosomal aberrations, time of aberration maxima and aberration spectra. HN2 (0.68 mg/kg b.w.), when given i.p., induced in ascites tumour cells a strong inhibition of mitotic frequency and very high aberration rates, whereas in bone marrow no aberrant chromosomes were observed. On the other hand, after s.c. administration, the same dose induced more aberrant metaphases in bone marrow than in tumour cells. Ara-C (315 mg/kg b.w.) resulted, after s.c. administration, in higher aberration frequencies both in ascites and bone-marrow cells compared with i.p. treatment. All ascites tumour cells showed higher aberration requencies than bone-marrow cells. In bone marrow the aberration maximum occurred as soon as 6 h after treatment. Furthermore, clear differences with respect ot the types of aberration found in the two systems were evident. The differences caused by the different modes of administration in two different types of cell are discussed in terms of metabolic inactivation and differences of the two tissues with respect to karyotype, cell cycle time and repair capacity.

Animals

Mutagenic activity of isoniazid in the mouse.

Isoniazid was tested for genetic activity in the mammalian spot test by treating in utero mouse embryos, derived from the crosses C57 B1/6J X T-stock and NMRI X DBA/2, heterozygous for various loci affecting coat color. Induction of genetic changes is seen by expression of recessive alleles in colored spots within the fur of the adult animal in a non-agouti background. Injecting mothers with isoniazid (100 mg/kg ip), an expression of recessive loci was found in 7.41% of the F1 animals in the cross C57 B1/6J X T-stock, while in the NMRI X DBA/2 cross 2.92% animals with recessive spots were detected. The control frequencies were respectively 0 and 0.78% animals with recessive spots. The positive control substance, ethyl methanesulfonate (100 mg/kg ip), yielded 5.97% and 4.71% animals carrying a recessive spot in the fur, respectively. These studies clearly demonstrate for the first time the induction of genetic damage other than cytological damage in somatic cells of mice by isoniazid.

Animals