Biomedical subjects

H Zitzelsberger

Publications and source records attributed to H Zitzelsberger.

44 records · Page 3Linked to original sources

PubMed1993

Radiation-induced chromosome aberrations analysed by two-colour fluorescence in situ hybridization with composite whole chromosome-specific DNA probes and a pancentromeric DNA probe.

Fluorescence in situ hybridization with composite whole chromosome-specific DNA probes for human chromosomes 1, 4 and 12 and a degenerate alpha-satellite pancentromeric DNA probe labelled with digoxigenin was used to measure symmetrical translocations and dicentrics induced in vitro by 137Cs gamma-rays (0-6.0 Gy) in peripheral lymphocytes. Despite subtracting our mean background translocation frequency of 0.0016 per cell (11,411 cells scored from 11 individuals) from induced frequencies, about 1.3-1.8-fold more translocations were found than dicentrics at a given dose. Translocation frequencies determined only in stable cells agree well with total translocation frequencies determined also in cells containing additional unstable chromosomal changes. The linear quadratic calibration curve generated for total stable translocations is based on approx. 17,000 cells. The suitability of this curve for biological dosimetry of human radiation exposure can now be evaluated in comparison with dose estimates based on a conventional dicentric dose-response curve.

Cesium Radioisotopes↗

PubMed1993

[Cytogenetic investigations in primary prostate carcinomas].

Primary cultures of 48 cases of prostate carcinoma were established. The expression of cytokeratin and prostate specific antigen were determined in the cultures routinely. G-banding analysis revealed some clonal numerical and structural aberrations: Trisomy 7 occurred in 4 cases, in one case in combination with a t(Y;22). Loss of the Y chromosome was found in 3 cases, in one case in combination with gain of chromosome #5. The most frequent clonal structural aberration var9(qh) occurred in 6 cases. A deletion of 6q(23) was found in two cases. None of these aberrations were found in normal tissue of the same patients. Numerical changes were demonstrated by fluorescence in situ hybridization (FISH) on native tissue, confirming the conventional cytogenetic findings.

Chromosome Aberrations↗

PubMed1992

Elevated p53 RNA expression correlates with incomplete osteogenic differentiation of radiation-induced murine osteosarcomas.

An important role for the p53 gene in osteogenic sarcomas has been imputed by identification of somatically acquired gene alterations in human osteosarcomas and by the development of osteosarcomas in p53 transgenic mice. To study the involvement of p53 in radiation-induced osteosarcomagenesis, we have investigated gene alterations and expression of p53 in radiation-induced murine osteosarcomas and tumor-derived cell lines. Eighteen of 31 tumors and 8 of 9 cells lines showed alterations in the p53 gene region, or elevated levels of p53 RNA. Expression of the osteoblast marker gene bone gla protein was substantially reduced in tumors which simultaneously showed high steady-state levels of p53 RNA. Our data indicate that p53, in addition to its function in regulating DNA synthesis, may be involved in the control of osteogenic differentiation in osteosarcomagenesis.

Animals↗

PubMed1992

Centromere detection in vinblastine- and radiation-induced micronuclei of cytokinesis-blocked mouse cells by using in situ hybridization with a mouse gamma (major) satellite DNA probe.

Non-isotopic in situ hybridization using a mouse gamma (major) satellite probe DNA was applied to detect centromeres in micronuclei, which were induced in vitro in mouse liver cells by ionizing radiation and by vinblastine sulfate. In a cytokinesis-blocked micronucleus assay a dose-dependent induction of micronuclei was found for both agents. After vinblastine exposure the observed micronuclei showed centromere-positive hybridization signals in an order of magnitude of 70-90%, but after radiation exposure the magnitude was only 10-20%. Since the in situ hybridization technique detects centromeric DNA directly, it can be used in a cytokinesis-blocked micronucleus assay for a rapid and reliable discrimination between aneuploidy-inducing and clastogenic agents.

Animals↗

PubMed1992

Radiation-induced chromosome aberrations analysed by fluorescence in situ hybridization with a triple combination of composite whole chromosome-specific DNA probes.

Fluorescence in situ hybridization (FISH) with a combination of three composite whole chromosome-specific DNA probes for human chromosomes 1, 4 and 12 was used to analyse in vitro radiation-induced dicentrics and symmetrical translocations in peripheral lymphocytes. Translocations could be rapidly and efficiently detected by FISH. Their frequencies were 1.8-fold higher than the frequencies for dicentrics at a given dose. The dose-response curves for translocations and dicentrics were linear quadratic with a significant higher quadratic component for translocations. The application of FISH for scoring stable translocations for biological dosimetry of radiation exposures is discussed.

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↗

PubMedDate not supplied

Interphase cytogenetics in pathology: principles, methods, and applications of fluorescence in situ hybridization (FISH).

Characteristic chromosome aberrations have been identified in various tumors. Fluorescence in situ hybridization (FISH) using specific probes that are generated by vector cloning or in vitro amplification and labeled with fluorescent dyes allow for the detection of these genetic changes in interphase cells. This technique, that is also referred to as "interphase cytogenetics", can be performed in cytological preparations as well as in sections of routinely formaldehyde-fixed and paraffin-embedded tissue. In cancer research and diagnostics, interphase cytogenetics by FISH is used to detect numerical chromosome changes and structural aberrations, e.g., translocations, deletions, or amplifications. In this technical overview, we explain the principles of the FISH method and provide protocols for FISH in cytological preparations and paraffin sections. Moreover, possible applications of FISH are discussed.

Cytological Techniques↗

PubMedDate not supplied

Comparative genomic hybridisation for the analysis of chromosomal imbalances in solid tumours and haematological malignancies.

Comparative genomic hybridisation (CGH) is based on a two-colour, competitive fluorescence in situ hybridisation of differentially labelled tumour and reference DNA to normal metaphase chromosomes. This new technology has made a great impact in molecular tumour pathology due to its possible application to archival specimens and the ability to create copy number karyotypes throughout the whole genome from very small amounts of DNA. If chromosomal imbalances can be correlated with a etiological and clinical features of tumours, CGH could be able to provide new prognostic and diagnostic criteria. CGH findings further provide starting points for the molecular genetic characterisation of altered chromosomal regions harbouring yet unidentified genes involved in tumorigenesis and tumour progression. An overview of the results of published CGH studies on solid tumours and haematological malignancies is presented. Methodological limitations of the CGH technology are reported, as well as future developments which will improve its use in routine analysis.

Chromosome Aberrations↗