Search PubMed⌕ Search

Biomedical subjects

M Bauchinger

Publications and source records attributed to M Bauchinger.

At least 91 records · Page 5Linked to original sources
PubMed1991

Mitotic spindle damage induced by 2-chlorobenzylidene malonitrile (CS) in V79 Chinese hamster cells examined by differential staining of the spindle apparatus and chromosomes.

A 3-h exposure of V79 Chinese hamster cells with the sensory irritant 2-chlorobenzylidene malonitrile (CS) caused apolar mitoses in a dose-dependent manner. With a preparation and staining technique that allows for the visualization of the spindle apparatus and the chromosomes it was found that unlike in Colcemid-induced c-metaphases residual spindle fibers or microtubule material were present in the majority of CS-induced c-metaphases. The observation suggests different mechanisms for the induction of the c-mitotic effect by the two spindle poisons.

Animals↗
PubMed1991

Induction of chromosome aberrations and sister chromatid exchange by indirectly acting mutagens in immortal mouse and rat hepatocyte lines.

Two immortalized, differentiated mouse (FMH-202) and rat (NRL-Cl-A) hepatocyte lines were examined for their capacity to activate the indirectly acting mutagens aflatoxin B1 (AFB1), cyclophosphamide (CP), benzo[a]pyrene (BaP) and 7,12-dimethylbenz[a]anthracene (DMBA) into DNA reactive metabolites as determined by the induction of structural chromosome aberrations (CA) and sister chromatid exchange (SCE). The rat and mouse hepatocyte lines were able to efficiently activate either AFB1, BaP and DMBA, or BaP and DMBA, respectively, as shown by significant clastogenic responses. SCE induction was apparent in both cell lines in response to each of the compounds. Due to the observed long-term maintenance of various liver specific functions (at least 3-4 years) as well as the capability to metabolize xenobiotics (at least 30 passages) these cells may be a suitable assay system for the detection of indirectly acting mutagens.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Analysis of the aneuploidy inducing capacity of 2-chlorobenzylidene malonitrile (CS) and metabolites in V79 Chinese hamster cells.

The aneuploidy inducing capacity of 2-chlorobenzylidene malonitrile (CS), a chemical used as a riot control agent, and its hydrolysis products o-chlorobenzaldehyde and malonitrile was studied at various exposure conditions in V79 Chinese hamster cells. Chromosomes were counted in metaphase preparations with preserved cytoplasm. A significant increase in the number of aneuploid cells was found after CS and o-chlorobenzaldehyde exposure but not after malonitrile exposure. o-chlorobenzaldehyde, which also introduced high levels of polyploid cells, seems to be an important metabolite for the aneuploidogenic effectiveness of CS.

Aneuploidy↗
PubMed1990

A case of malignant mastocytosis with near-haploid, near-diploid, and polyploid cells in the bone marrow.

Chromosome analysis in bone marrow cells of a 41-year-old woman with malignant mastocytosis (MM) revealed near-haploid (59%), near-diploid (36%), and polyploid (5%) cells. Near-haploid cells had a mode of 25 chromosomes with variable disomy and nullisomy of particular chromosomes. Disomy for chromosome 19 and chromosome 20 were most common. A 17p+ marker was observed in all cells. Other structural chromosomal changes were dicentrics, ring chromosomes, translocations, and double minutes. The modal chromosome number in near-diploid cells was 46 with a range of 41-52. The majority of cells with 46 chromosomes were pseudodiploid and only a few had a normal female karyotype. As in near-haploid cells, various structural chromosomal changes were found. The 17p+ marker was also present in occasional cells suggesting a relationship between the two tumor cell populations. Chromosome numbers in polyploid cells ranged from 70 to about 600. Identical copies of dicentrics or markers were identified in some cells.

Adult↗
PubMed1990

Cytogenetic and molecular analysis of a "masked" Philadelphia chromosome in chronic and blastic phases of chronic myeloid leukemia.

A "masked" Philadelphia chromosome (Ph), t(1;22;9)(p32;q11;q34), was found in the bone marrow and peripheral blood cells of a patient with chronic myeloid leukemia (CML) during the chronic and blastic phases of the disease. As an additional change, a reciprocal translocation t(12;13)(p13;q14) was observed in the blastic phase. Southern blot analysis showed a rearrangement of the breakpoint cluster region (bcr). Northern blot analysis with a c-abl probe showed an abnormal 8.5 kb c-abl RNA transcript in addition to the normal 6- and 7-kilobase (kb) c-abl species. Thus, the results demonstrate the presence of a c-abl/bcr rearrangement in the masked Ph corresponding to that observed in the standard Ph translocation t(9;22)(q34;q11) of CML.

Blast Crisis↗
PubMed1990

Philadelphia chromosome-negative acute hematopoietic malignancy: ultrastructural, cytochemical and immunocytochemical evidence of mast cell and basophil differentiation.

We describe a patient with fever and multiple osteolytic bone lesions accompanied by hypercalcemia, a duodenal ulcer, anemia, and thrombocytopenia. Bone marrow showed a dense infiltration by abnormal cells characterized by small basophil granula, erythrophagocytosis and nuclear atypia. These cells were positive for toluidine blue and partly for myeloperoxidase and chloroacetate esterase, expressed myeloid differentiation markers, and exhibited multiple numerical and structural chromosome aberrations. Molecular genetic analysis showed no breakpoint cluster region rearrangement. Electron microscopy demonstrated granula both of basophil and mast cell type. Concluding, in this patient an acute hematopoietic malignancy with many features of malignant mastocytosis but also with signs of a basophil differentiation. This is further support for a hematopoietic stem cell origin of human mast cells.

Adult↗
PubMed1990

Chromosome aberrations induced in human lymphocytes by 16.5 MeV protons.

In a track segment irradiation experiment with 16.5 MeV protons the induction of dicentrics was studied in human T-lymphocytes. The dose-response relationship was linear quadratic with estimated parameters alpha = (0.44 +/- 0.07) x 10(-1) Gy-1 and beta = (1.95 +/- 0.30) x 10(-2) Gy-2. With respect to X-rays a limiting RBE of 1.1-1.2 exists. The present findings are compared with data from other laboratories obtained with 4.9 and 8.7 MeV protons. It was found that the data do not fit theoretical predictions on a proportional relationship between alpha values and LET. Using the microdosimetric quantity yD (25 nm), the dose average of the lineal energy, for characterization of these proton radiations, at a relevant site diameter of 25 nm the ratio of yD = 1.15 is in accordance only with the observed alpha ratio of 1.0 +/- 0.23 for 8.7 and 16.5 MeV protons. In contrast to the prediction of a constant beta at low LET values, the quadratic coefficients increase with increasing LET between 3 and 8 keV/microns.

Chromosome Aberrations↗
PubMed1990

Mitotic spindle damage induced by 3,4-dichloroaniline in V79 Chinese hamster cells examined by differential staining of the spindle apparatus and chromosomes.

3,4-Dichloroaniline (3,4-DCA), an intermediate in various chemical syntheses, has been detected as an environmental contaminant in surface waters and in the effluents from dye manufacturing plants. Previously we showed that the compound caused mitotic spindle damage. In the present study a preparation and staining technique has been used that allows a direct examination of the spindle apparatus and chromosome behaviour of 3,4-DCA-exposed V79 Chinese hamster cells. After a 3 h exposure the compound caused monopolar mitoses and metaphase arrest in a dose-dependent manner, most probably by interfering with centriole separation. At a concentration of 1 mM, increased levels of aneuploid cells could be observed in cells exposed for two cell division cycles.

Aneuploidy↗
PubMed1989

Screening for interindividual differences in radiosensitivity by means of the micronucleus assay in human lymphocytes.

The response of unstimulated peripheral lymphocytes to a single dose of 3 Gy of 137Cs gamma rays was analysed in blood samples from 30 donors by a conventional micronucleus assay and from 14 donors by the cytokinesis-block (CB) method. Significant interindividual variations could be detected for the baseline levels and for induced levels of micronuclei. An age effect could be demonstrated with the conventional method for the number of spontaneous MN, but not with the CB method. The corresponding numerical estimate was 3.4 +/- 1.3% increase per year. No such increase was apparent for induced frequencies. Provided that cell proliferation kinetics is reliably taken into account the micronucleus assay could be helpful for diagnosing potential radiosensitive individuals.

Adult↗
PubMed1989

Time-effect relationship of chromosome aberrations in peripheral lymphocytes after radiation therapy for seminoma.

The time-effect relationship of dicentrics and cells containing unstable chromosome abnormalities (Cu cells) was studied in peripheral lymphocytes of 40 blood samples from 23 patients suffering from seminoma during a time period of 0-1720 days after radiation therapy. Nine patients were studied before treatment. Since the half-time for the disappearance of damaged cells from circulating blood is an increasing function of post-exposure time it can only be expressed as a differential value. The present model discriminates between the mean lifetime m for lymphocytes and a parameter q which is the differential half-time for the decline of damaged cells immediately after exposure (t = 0). If the time t is short compared with m the decline is asymptotically time-hyperbolic rather than exponential and can be described by q only. According to recalculations of previous data, comprising 30 years post exposure, m approximates 10 years. Differential half-times can be derived for any time post treatment within the analysed time period for the decline of the incidence of dicentrics. For example at the end of therapy (t = 0) the differential half-time was calculated to be 0.4 years and at 1720 days post exposure 3.6 years resulted. The corresponding values for the percentage of Cu cells cannot be derived for t = 0; at 1720 days 3.9 years resulted.

Adult↗
PubMed1989

Absence of adaptive response to low-level irradiation from tritiated thymidine and X-rays in lymphocytes of two individuals examined in serial experiments.

No adaptation-like response to the induction of chromatid breaks could be demonstrated for lymphocytes of 2 donors pretreated with tritiated thymidine or 0.01 Gy of X-rays and subsequently exposed to a challenge dose of 1.5 Gy of X-rays. The absence of an adaptive response was already observed for these 2 donors in earlier experiments and is confirmed here under various experimental conditions.

Adaptation, Physiological↗
PubMed1989

Cytogenetic effects of 3,4-dichloroaniline in human lymphocytes and V79 Chinese hamster cells.

3,4-Dichloroaniline (3,4-DCA), an intermediate in various chemical syntheses, has been detected as an environmental contaminant in surface waters and in the effluents from dye-manufacturing plants. Tested for clastogenicity in human lymphocytes in vitro the compound was inactive in the chromosome aberration assay yet exhibited a positive sister-chromatid exchange response in the presence of a mammalian metabolic activation system. Exposure of V79 Chinese hamster cells to 3,4-DCA caused a concentration-dependent increase in the incidence of spindle disturbances, predominantly of the initial c-mitotic type. The results indicate that 3,4-DCA might induce aneuploidy in mammalian cells by interaction with the mitotic apparatus.

Aniline Compounds↗
PubMed1989

2-Chlorobenzylidene malonitrile (CS) causes spindle disturbances in V79 Chinese hamster cells.

Exposure of V79 Chinese hamster cells to 2-chlorobenzylidene malonitrile (CS), a chemical used as a sensory irritant for riot control, caused a concentration-dependent increase in the incidence of spindle disturbances. A C-mitotic effect with the appearance of C-metaphases, a metaphase block and the concomitant disappearance of ana-telophase figures were observed after a 3-h treatment. The results indicate that CS might induce aneuploidy in mammalian cells by interacting with the mitotic apparatus.

Animals↗
PubMed1989

Adaptive response after X-irradiation of human lymphocytes?

The induction of an adaptive response of human lymphocytes from three donors exposed to 0.01 or 0.05 Gy of X-rays at 32 h of culture and to 1.5 Gy at 48 h was studied. There was no evidence for a significant reduction of the incidences of chromosomal aberrations in cultures pre-treated with low doses and subsequently exposed to the higher dose compared with cultures exposed to the high dose alone.

Adaptation, Physiological↗
PubMed1989

Myeloablative conditioning for marrow transplantation in myelodysplastic syndromes and paroxysmal nocturnal haemoglobinuria.

Paroxysmal nocturnal haemoglobinuria (PNH) and myelodysplastic syndromes (MDS) are disorders of pluripotent stem cells resulting in haematopoietic insufficiency which can be cured by marrow transplantation. The extent of myeloablative conditioning necessary for elimination of the non-malignant and premalignant clones is not known. We report our results of marrow transplantation with and without myeloablative conditioning in two patients with PNH and seven patients with MDS. Conditioning was not used in a patient with PNH and a monozygotic twin as donor. In this patient the disease remained unchanged. Myeloablative treatment with busulphan (BUS) in addition to immunosuppression with cyclophosphamide (CY) was used for conditioning in a patient with PNH and a 2-year-old boy with chronic myelomonocytic leukaemia (CMML). Fractionated total body irradiation (FTBI) and CY was used in six patients with refractory anaemia with excess of blasts (RAEB) and RAEB in leukaemic transformation (RAEB-T). Haematopoiesis was fully restored in all patients conditioned with myeloablative treatment except for a patient in leukaemic transformation with myelofibrosis and a HLA-DR-incompatible donor. Chimerism was complete in all patients except for the 2-year-old boy conditioned with BUS and CY. Our results and those reviewed in the literature indicate that myeloablative conditioning with either BUS or FTBI is advantageous for marrow transplantation in PNH and MDS.

Adult↗
PubMed1988

Direct analysis of the clastogenic effect of formaldehyde in unstimulated human lymphocytes by means of the premature chromosome condensation technique.

The cytogenetic effect of formaldehyde (FA) on unstimulated human lymphocytes was studied by means of conventional chromosome analysis and the premature chromosome condensation (PCC) technique. In first post-treatment metaphases no significantly increased yields of chromosomal changes could be observed. The analysis of PCCs, however, showed high yields of chromosome fragments. Bleomycin (BLM) used as positive control was also highly clastogenic in PCCs and resulted in significantly increased yields of chromosome-type aberrations. As recently argued, a premitotic selection against heavily damaged cells could be an explanation for the discrepancy between the chromosome findings in metaphase and PCC analysis after FA treatment. In addition, a differential effectiveness may exist in unstimulated lymphocytes to convert multiple fragmentation into chromatid- or chromosome-type aberrations through S-phase-dependent or S-phase-independent mechanisms.

Animals↗
PubMed1988

Analysis of the cytogenetic effect in human lymphocytes induced by metabolically activated 1- and 2-methylnaphthalene.

Chromosome analyses were carried out in human lymphocytes treated in vitro with 1- and 2-methylnaphthalene (1-MN, 2-MN) in the presence and absence of the mammalian metabolic activation system, S9 mix. Without S9 mix there was no indication of induction of any significant cytogenetic effect by either compound. With S9 mix a weak clastogenic effect was apparent at 4 mM 2-MN only and sister-chromatid exchange frequencies were significantly increased at each dose of 1- and 2-MN, yet always less than twice the control level. The present observations do not indicate that 1- and 2-MN must be classified as potential genotoxic substances.

Biotransformation↗