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Biomedical subjects

L Sabatier

Publications and source records attributed to L Sabatier.

7 recordsLinked to original sources

Chromosomal anomalies in radiation-induced fibrosis in the pig.

R-banded karyotypes were established on fibroblasts from fibrotic tissues derived from experimental fibrosis induced in pigs, either surgically or by 64 Gy of gamma-rays from iridium-192. No chromosome aberrations were observed in the surgical fibrosis. In radiation-induced fibrosis, the high frequency of abnormal karyotypes and the frequent complexity of the chromosomal rearrangements suggest that the fibroblasts originated either from the 64-Gy area, or from the penumbra, but certainly not from non-irradiated areas. At early passages in vitro, almost all karyotypes were different, demonstrating a multiclonal origin of fibrotic tissue. At late passages (above 24), the situation was quite different, with the persistence of one or two clones only, demonstrating a strong selective pressure occurring in vitro.

Animals

Early superoxide dismutase alterations during SV40-transformation of human fibroblasts.

The expression of superoxide dismutases (SOD) 1 and 2 was studied in 4 clones of human fibroblasts after their infection by simian virus 40 (SV40), in parallel with the alterations of chromosomes 21 and chromosome 6q arms, carrying the genes that encode for SOD1 and SOD2 respectively. For all clones, a similar scheme with 2 main phases was observed for both chromosome and SOD variations. The first phase, defined as the pre-crisis phase, was characterized by chromosomal instability, but maintenance of normal numbers of chromosome 6q arms and chromosomes 21. The level of SOD2 mRNA was high, while SOD2 activity and immunoreactive protein were low. SOD1 protein and activity were decreased. In the second phase, defined as the post-crisis phase, the accumulation of clonal chromosomal rearrangements led to the loss of 6q arms, while the number of chromosomes 21 remained normal. SOD2 mRNA level was decreased and SOD2 immunoreactive protein and activity remained low. SOD1 protein and activity increased with passages, reaching values similar to those of control cells at late passages. As in established SV40-transformed human fibroblast cell lines, good correlation was found between SOD2 activity and the relative number of 6q arms. These results allow us to reconstruct the sequence of events leading to the decrease of SOD2, a possible tumor-suppressor gene, during the process of SV40-transformation of human fibroblasts.

Cell Transformation, Viral

SOD2: a new type of tumor-suppressor gene?

The activity of superoxide dismutases (SOD) 1 and 2 was analysed in correlation with mRNA and chromosome content in 6 SV40-transformed (TF) and in non-transformed (NF) human fibroblast cell lines. Total SOD activity was fairly constant, whereas the ratio SOD2/SOD1 was much lower in TF than in NF. The decrease in SOD2 activity was correlated with a low mRNA content, and with the presence of various chromosomal rearrangements leading to deletions of the long arm of chromosome 6 where the gene is mapped. In contrast, chromosome 21, carrying the gene for SOD1, was not found to be deficient and the SOD1 activity was high. This shows that in TF, the activity of SOD2 is largely determined by gene dosage. It has been proposed that SOD activity could be inversely correlated with cell proliferation, and that SOD2 activity, in particular, was related to cell differentiation. Thus, there is a cascade of events occurring in cell transformation, involving gene deregulation, chromosome (gene) deletion, low mRNA and protein content, low enzyme activity, and acquisition of growth advantage which makes the SOD2 gene a possible new type of tumor-suppressor gene.

Cell Line, Transformed

Chromosome aberration dosimetry: addition of thymidine, an interesting mean to increase the number of dividing cells.

Addition of thymidine to culture medium commonly used by laboratories performing medical cytogenetics followed by a release of the block by 2-deoxycitidine increases greatly the mitotic index and the proportion of metaphases suitable for chromosome analysis. The benefit is, however, less evident when the method is applied to culture medium used in laboratories specialized in chromosome aberration dosimetry.

Cell Division

The decrease of catalase or esterase D activity in patients with microdeletions of 11p or 13q does not increase their radiosensitivity.

Lymphocyte cultures from patients affected by retinoblastoma (Rb), with or without a microdeletion of chromosome 13, and Wilms tumor (WT), with a microdeletion of chromosome 11p where exposed to gamma-ray radiation during S and G2 phases. Chromatid and chromosome lesions were scored and compared to those observed in controls. No significant differences were detected, neither between patients and controls, nor between patients carrying or not a microdeletion. This lack of difference was unexpected since the genes for catalase and esterase D, also called S-formyl glutathione hydrolase, which are two detoxication enzymes, are deleted in case of microdeletion of 11p and 13q, respectively.

Acatalasia

How are sticky chromosomes formed?

Blood lymphocytes in culture were irradiated by gamma-rays 3 h to 30 mn before harvesting. The various induced lesions were analysed, with a particular attention on sticky chromosomes, i.e. radial figures in which chromosomes are not obviously broken, but are linked by a tiny filament. Such anomalies are preferentially induced in mid to late G2-phase. They result from recombinations occurring at nonrandom chromosome regions: junction between hetero- and euchromatin, and telomeric regions. It is proposed that they are formed when double strand breaks are induced while intrachromatidic links have started to be formed in the course of chromosome condensation. If this interpretation is correct, the apparent lack of induced breakage of premitotic chromosomes is artifactual.

Cells, Cultured