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Biomedical subjects

M Bauchinger

Publications and source records attributed to M Bauchinger.

At least 109 records · Page 6Linked to original sources

1,6-Dinitropyrene causes spindle disturbances and chromosomal damage in V79 Chinese hamster cells.

We have investigated the cytogenetic effect of 1,6-dinitropyrene (1,6-DNP) in Chinese hamster V79 cells. The chemical caused a dose-dependent increase in the incidence of initial and full C-mitoses, polyploid mitoses, ana-telophases with lagging chromosomes, non-disjunction and multipolar configurations, in a range of 0.05-5 microM. These findings indicate that 1,6-DNP interferes with the functioning of the spindle apparatus in V79 cells. Early signs of spindle disturbances were seen at 1,6-DNP concentrations which only moderately reduced cell growth and division. Analysis of structural chromosomal aberrations revealed the appearance of chromatid-type aberrations with open breaks and exchanges accompanied by gaps. The results indicate that 1,6-DNP is both a spindle-disturbing and a clastogenic agent in V79 cells.

Animals↗

Genotoxicity of 2-nitropropane and 1-nitropropane in Salmonella typhimurium and human lymphocytes.

A 10- and 12-fold increase of revertant numbers could be demonstrated for 2-nitropropane (2-NP of greater than 99% purity) tested in the preincubation assay with Salmonella typhimurium strains TA 100 and TA 98 in the presence and absence of S9 mix. In the nitroreductase-deficient strains TA 100NR and TA 98NR, 2-NP was less mutagenic than in the parent strains. In human lymphocytes the induction of a weak clastogenic effect and of sister chromatid exchanges required exogenous metabolic activation. No significant mutagenic or cytogenetic response was found with 1-nitropropane of 97% purity in S. typhimurium or human lymphocytes.

Alkanes↗

The effectiveness of S9 and microsomal mix on activation of cyclophosphamide to induce genotoxicity in human lymphocytes.

Comparative results are presented on the effectiveness of rat-liver S9 or microsomal mix (M mix) in activating cyclophosphamide (CP) and its ability to induce a clastogenic effect in human lymphocytes in vitro. Structural chromosome changes were analysed exclusively in 1st division (M1) metaphases post-exposure. A high genotoxic response was observed for both metabolizing systems used. With an exposure of 2 h to different concentrations of S9 or M mix, the highest aberration yields were always found for the highest protein content. For CP treatment times of 1, 2 or 4 h together with S9 mix (protein content 10 mg/ml) or M mix (4 mg/ml), the latter was more efficient. With both systems, a lower clastogenic effect of CP was found at 4 h exposure than at 1 h or 2 h. Only a weak cytotoxic effect, reflected mainly by the reduction in the percentage of 3rd cycle cells (M3), and measured in terms of the proportion of M1, M2 and M3 cells, was induced by both systems.

Animals↗

Analysis of cytogenetic effect in human lymphocytes induced by metabolically activated 2-nitropropane.

Chromosome analyses were carried out in human lymphocytes treated in vitro with 2-nitropropane (2-NP) in the presence and absence of the mammalian metabolic activation system, S9 mix. Without S9 mix, only the frequency of gaps was significantly increased at 80 mM 2-NP as compared to controls. With S9 mix, the incidences of gaps and chromatid-type aberrations were significantly increased at 60 mM and 80 mM. Sister-chromatid exchanges (SCE) have been induced at concentrations as low as 7.5 mM. The present findings demonstrate that in human lymphocytes, 2-NP requires metabolic activation to express clastogenicity and SCEs.

Alkanes↗

Cell survival and radiation induced chromosome aberrations. I. Derivation of formulae for the determination of transmission and survival parameters of aberrations.

Existing mathematical formulations to predict the frequency of radiation induced chromosome aberrations in 2nd post-irradiation division are based on the Poisson distribution [3, 4]. Meanwhile several studies have shown that intercellular distributions exist, deviating from Poisson. In the present study a modified model was developed which permits the application of empirical distributions. Transmission and survival parameters of aberrations can be iteratively computed. A general formula was derived for the calculation of cell survival from 1st to 2nd division.

Cell Survival↗

Cell survival and radiation induced chromosome aberrations. II. Experimental findings in human lymphocytes analysed in first and second post-irradiation metaphases.

Human peripheral lymphocytes were irradiated in whole blood with 0.5-4.0 Gy of 220 kVp X-rays and the frequency of chromosome aberrations was determined in 1st or 2nd division metaphases discriminated by fluorescence plus giemsa staining. Using the empirical distributions of aberrations among cells, cell survival and transmission of aberrations were investigated. Considering both daughter cells, we found that 20% of fragments and 55% of dicentrics or ring chromosomes are lost during the 1st cell division; i.e. cell survival rate from 1st to 2nd generation is mainly influenced by anaphase bridging of these two-hit aberrations. Cell survival to 2nd mitosis was calculated considering this situation and compared with the survival derived from the fraction of M 1 cells without unstable aberrations. The resulting shouldered survival curves showed significantly different slopes, indicating that cell reproductive death is overestimated in the latter approach.

Biometry↗

Formaldehyde-induced cytotoxic, genotoxic and mutagenic response in human lymphocytes and Salmonella typhimurium.

The incidences of chromatid-type aberrations and sister-chromatid exchanges were significantly increased in human lymphocytes treated with formaldehyde (FA) in vitro. In the presence of the mammalian metabolic activation system, i.e. S9 mix, the yields were reduced, although not to control levels. With S9 mix the structural chromosome damage induced by exposure to 1.0 mM FA was qualitatively and quantitatively identical to that induced by 0.05 mM cyclophosphamide (used as positive control for metabolic activation). Cell proliferation was clearly reduced with or without the presence of S9 mix. In a plate assay with Salmonella typhimurium strain TA100 in the absence and presence of S9 mix, a weak mutagenic response was observed. Using the pre-incubation method, FA induced without S9 mix a 1.6-fold and with S9 mix a 2.7-fold increase of revertant numbers over controls.

Animals↗

Storage of irradiated human blood; a source of error in quantitative chromosome analysis.

Human whole blood was irradiated with 2.5 Gy of 220 k Vp X-rays and stored before culture with 9.7 microM BrdU and 19.4 or 38.7 microM BrdU for 0, 24, 48 and 72 h. The frequency of dicentrics and ring chromosomes was determined in cells staining as first division (M1) metaphases with the fluorescence plus Giemsa technique. Storage had no influence on the observed aberration yields in 44 h cultures containing 9.7 microM BrdU. In 66 h cultures at 19.4 microM BrdU the observed yields after 2 and 3 days' storage were significantly lower as compared to cultures from fresh blood. No storage effect was revealed in 66 h cultures containing 38.7 microM BrdU. In cases where cytogenetic radiation dosimetry has to be carried out using blood samples which have been in transit for 2-3 days, the findings are of relevance for a correct determination of the chromosome damage in M1 cells.

Blood Preservation↗

Cytogenetic effects in lymphocytes of formaldehyde workers of a paper factory.

Chromosome analyses were carried out in lymphocytes from 20 male papermakers exposed to formaldehyde (FA) for 2-30 years. 20 male workers from the same factory but without FA exposure served as controls. In the exposed group a significantly increased incidence of dicentrics or dicentrics and ring chromosomes was observed for 11 workers currently employed as supervisors. In contrast to 9 operators their total mean exposure time to FA was about 2.5 times longer. No significantly higher SCE values were found for smoking or for non-smoking FA workers compared with the corresponding control subjects.

Adult↗

Trisomy 7 and 8 in Ph-negative chronic eosinophilic leukemia.

The results of cytogenetic analyses of bone marrow and peripheral blood cells in a 67-year-old male with chronic eosinophilic leukemia (EL) are described. Although the patient showed leukocytosis with marked eosinophilia, initial chromosome findings in bone marrow revealed a normal male karyotype. Seven months later, more than 80% of bone marrow cells had a hyperdiploid karyotype (48,XY, +7, +8), the remaining cells being normal. Seven weeks later, the identical abnormal karyotype was observed in about 30% of banded metaphases of stimulated peripheral blood cells. No mitoses were found in unstimulated cultures. No Ph chromosome was observed. So far, trisomy 8 has been described for only two cases of EL, whereas trisomy 7 has never been observed.

Aged↗

Chromosome aberrations in human lymphocytes induced by fission neutrons.

The dose-response relationships of dicentrics and excess acentrics were analysed after exposure of human lymphocytes to a mixed fission neutron-gamma-ray beam. From the analysis of exclusively first division cells a linear-quadratic relation was obtained for dicentrics with the ratio of linear and quadratic components, zeta, equal to 2.76 Gy. Over the range of doses studied (0.04-1.97 Gy) intratrack events therefore predominated. This also applied to acentrics which were linearly related to dose. At the lowest level of observed effect and dose, r.b.e. values with respect to 60Co gamma-rays of up to about 11 were derived for dicentrics and acentrics. With increasing neutron dose the r.b.e. decreased.

Chromosome Aberrations↗

Trisomy 1q and loss of Y chromosome in a male with osteomyelosclerosis.

The results of a cytogenetic analysis of peripheral blood cells in a 61-year-old male with histopathologically documented osteomyelosclerosis, hepatosplenomegaly, ascites and anemia are described. The karyotype 46,X,-Y +1 p22----qter, without Ph1-chromosome, was observed in all unstimulated and in most PHA-stimulated cells. The patient had not received cytostatic or radiation therapy, thus the marker 1q + could not have resulted from such clastogenic treatments.

Chromosomes, Human, 1-3↗

Chromosome aberrations induced in patients treated with chemotherapeutic drugs and irradiation for acute lymphatic leukemia.

Chromosome analyses were carried out in lymphocytes of ten children with ALL, prior to and during combined therapy with antineoplastic drugs and cranial irradiation. Chromosome preparations from group I (four patients) were analysed by conventional staining. For group II (six patients) the FPG technique (fluorescence plus Giemsa) was applied after BrdU treatment of cultures and cells were scored exclusively in first division. A significant clastogenic effect could not be detected in samples collected during or after chemotherapy for either group. After cranial irradiation of those patients in group II. linear dose-effect relationships for dicentric plus ring chromosomes, and for excess acentrics, could be demonstrated after correction for the relative amount of irradiated volume.

Adolescent↗

Weighted identity test for the comparison of dose-response functions of radiation-induced chromosome aberrations.

For the analyses of dose-relations of radiation-induced chromosome aberrations a weighted least squares method has to be carried out since the variance of observed aberration yields are different at different doses. Consequently identical statistical weights have to be used for the comparison of dose-response functions. For this reason a weighted identity test is presented. The derivation of the test quantity is described in a generalized form. The practical application of the test and the computation of the test quantity is shown for the linear and linear-quadratic model.

Chromosome Aberrations↗