Biomedical subjects

L Sabatier

Publications and source records attributed to L Sabatier.

63 records · Page 4Linked to original sources

PubMed1988

Transmission of radiation-induced rearrangements through cell divisions.

A BrdU incorporation technique associated with heat denaturation, acridine orange staining and UV irradiation, was applied to G0-irradiated lymphocyte cultures. This made it possible both to obtain an R-banding, and to estimate the number of divisions undergone by each cell in mitosis irradiation. Cell survival and slowing down of the cell cycle could be distinguished. The frequency of various types of rearrangements, and their association was studied at each cell division. It is shown that the loss of cells carrying chromosomal rearrangements is determined by several parameters such as the presence of dicentric or multicentric chromosomes and above all the association of several rearrangements in the same cell.

Cell Cycle↗

PubMed1988

Influence of time and cell cycle phase on radiation-induced chromosome lesions.

Human lymphocytes were irradiated with gamma-rays every hour from 7 to 1 h before harvesting. BrdU was added to the cultures immediately after irradiation to estimate the cell cycle phase by studying replication band patterns for each analysed metaphase. The average number of lesions has been observed to be more related to the time elapsed between irradiation and harvesting than to the cell phase. However, the types of lesions i.e. chromatid, chromosome breaks and chromatid exchanges are closely dependent on the phase. Cells irradiated 2 h before harvesting exhibit 3 and 6 times more lesions than those irradiated 3 and 7 h before harvesting respectively. This high sensitivity of cells, 2 h before harvesting, is observed for cells irradiated during late S as well as during G2 phase.

Cell Cycle↗

PubMed1987

Different reactivity of Z-DNA antibodies with human chromosomes modified by actinomycin D and 5-bromodeoxyuridine.

Antibodies against Z-DNA react with fixed metaphase chromosomes of man and other mammals. Indirect immunofluorescence staining shows that chromosomal segments corresponding to R- and T-bands preferentially fix Z-DNA antibodies. In this work Z-DNA antibodies were used as a probe for DNA conformation in euchromatin of fixed human chromosomes whose condensation or staining were modified by actinomycin D (AMD) and by 5-bromodeoxyuridine (BrdU). Treatments with AMD and BrdU were performed to induce a G-banding by modification of chromosomal segments corresponding to R- and T-bands. Long BrdU treatments were used to induce asymmetrical and partially undercondensed chromosomes by substitution of thymidine in one or both DNA strand. Our results show a clear difference of Z-DNA antibodies reactivity after AMD or BrdU treatment. The G-banding obtained after AMD treatment is not reversed by Z-DNA antibodies staining since these antibodies bind very weakly to the undercondensed R-bands. On the other hand, the G-banding obtained by BrdU is completely reversed giving typical R-banding, as on untreated chromosomes. For asymmetrical chromosomes an R-, T-banding pattern is always observed but there is a decrease of the fluorescence intensity proportional to the degree of BrdU incorporation. We conclude that AMD treatment greatly disturbs Z-DNA antibodies binding suggesting a change in DNA conformation, whereas BrdU treatments do not suppress but only weaken the specific binding of Z-DNA antibodies on R- and T-bands. The direct involvement of thymidine substitution in DNA sequences recognized by Z-DNA antibodies is discussed.

Antibodies↗

PubMed1987

Qualitative study of chromosomal lesions induced by neutrons and neon ions in human lymphocytes at G0 phase.

Chromosomal lesions, mitotic index and cell cycle progression delay induced by neutron (protons 34 MeV on beryllium) and neon (250 MeV/i) particles are studied in human lymphocytes. The cell cycle progression is slightly decreased at a dose of 1 Gy. Mitotic indexes are significantly decreased after irradiation by the different particles, except neon in 52-h cultures. By comparison to chromosome damages caused by gamma-rays, previously published, it is found that the lesions observed here are frequently more complex: the number of breaks is higher per abnormal mitosis and higher per rearrangement on the average. This complexity is higher for neon ions than for neutron beams.

Cell Cycle↗

PubMed1986

Radiation induced inversions in human somatic cells.

Peri- and paracentric inversions induced by various types of ionizing radiation (gamma and alpha-rays, neutron and neon beams) are analysed. Their frequencies significantly increase for radiation doses greater than or equal to .5 Gy. Their distribution does not seem to be at random. Pericentric are detected 3 to 4 times more frequently than paracentric inversions. Some identical inversions are recurrently induced. A proportion reproduces inversions detected in human cytogenetics laboratories and a larger proportion, chromosomes of other primate species. It seems that breakages, which numbers are roughly proportional to chromosome lengths, lead to reassociations with a limited number of combinations.

Alpha Particles↗

PubMed1986

Inversions in evolution of man and closely related species.

By the comparative study of the karyotypes of many Primates, 35 inversions (25 peri- and 10 paracentric) having accumulated during evolution of species related to man were reconstructed. Some of them originated human chromosomes from more ancestral chromosomes still present in other primate species. Their detection in man would indicate the occurrence of reverse mutations. Other inversions occurred in ancestral chromosomes identical to those of man, and originated chromosomes of other Primates species. Their detection in man would indicate the occurrence of a convergent mutation. It is shown that such reverse and convergent mutations do occur. They are too frequently observed than by mere chance among patients ascertained in human cytogenetic laboratories. Their excess is still larger among radiation induced inversions in human cells. This demonstrates the nonrandom occurrence of inversions. In addition, it is concluded that inversions which have accumulated during evolution are more representative of mutagenesis than those detected in human cytogenetic laboratories.

Animals↗

PubMedDate not supplied

Chromosomal and enzymatic patterns provide evidence for two types of human colon cancers with abnormal nucleotide metabolism.

Correlated chromosomal and enzymatic studies are reported in a series of 13 human colon cancers. Two distinct chromosomal patterns are found: one with many losses, called monosomic type and another with many gains, called trisomic type. Chromosome 18, which carries the gene for thymidylate synthase (TS) is always missing in the monosomic type, in which TS activity is low. On the contrary, TS activity is high in the trisomic type on the average. The long arm of chromosome 17, which carries the gene for thymidine kinase (TK), is frequently duplicated in both monosomic and trisomic types, in which TK activities are high. It is found that most other deletions affect chromosomes carrying genes for enzymes of the de novo pathways whereas most other gains affect chromosomes carrying genes for enzymes of salvage pathways for synthesis of nucleotides. The importance of this finding is discussed.

Adenocarcinoma↗

PubMedDate not supplied

The relationship between spontaneous telomere loss and chromosome instability in a human tumor cell line.

Chromosome instability plays an important role in cancer by promoting the alterations in the genome required for tumor cell progression. The loss of telomeres that protect the ends of chromosomes and prevent chromosome fusion has been proposed as one mechanism for chromosome instability in cancer cells, however, there is little direct evidence to support this hypothesis. To investigate the relationship between spontaneous telomere loss and chromosome instability in human cancer cells, clones of the EJ-30 tumor cell line were isolated in which a herpes simplex virus thymidine kinase (HSV-tk) gene was integrated immediately adjacent to a telomere. Selection for HSV-tk-deficient cells with ganciclovir demonstrated a high rate of loss of the end these "marked" chromosomes (10-4 events/cell per generation). DNA sequence and cytogenetic analysis suggests that the loss of function of the HSV-tk gene most often involves telomere loss, sister chromatid fusion, and prolonged periods of chromosome instability. In some HSV-tk-deficient cells, telomeric repeat sequences were added on to the end of the truncated HSV-tk gene at a new location, whereas in others, no telomere was detected on the end of the marked chromosome. These results suggest that spontaneous telomere loss is a mechanism for chromosome instability in human cancer cells.

Base Sequence↗

PubMedDate not supplied

Chromosomal DNA and p53 stability, ubiquitin system and apoptosis in B-CLL lymphocytes.

The ubiquitin system regulates diverse biological processes such as DNA replication and repair, biogenesis of ribosome, peroxisome and nucleosome, cell cycle, stress response and signal transduction pathways. Thus, the reported role of the ubiquitin system in apoptotic death control as well the alteration of its control in carcinogenesis should come as no surprise. Indeed, we and other groups have reported that the ubiquitin system is involved in apoptotic cell death of normal human lymphocytes and that this control is altered in B lymphocytes derived from chronic lymphocytic leukemia patients (B-CLL), rendering these malignant cells hypersensitive to specific inhibition of protein degradation/processing through proteasomal function. This approach recently allowed us to demonstrate that the stability of the tumor suppressor and pro-apoptotic protein p53 is differentially regulated in B-CLL versus normal lymphocytes and that this difference might at least partly explain the impaired response of B-CLL lymphocytes to apoptotic death activation. These results strongly suggest an imbalance in p53 regulation in B-CLL cells that leads to a variable response to DNA damage and constitutively expressed chromosomal instability. The question we and others would like to address is whether this alteration, or more likely a subset of alterations of the ubiquitin-proteasome pathway, is specific to B-CLL malignancy or if it is a hallmark of cancer cells in general. In either case, a better understanding of the ubiquitin-dependent control of apoptosis should pave the way towards a methodological approach for in vitro development of discriminating treatments which may be of potential usefulness in clinical trials of B-CLL.

Apoptosis↗