Biomedical subjects

M Ricoul

Publications and source records attributed to M Ricoul.

24 records · Page 2Linked to original sources

PubMed1992

Jumping translocations originate clonal rearrangements in SV40-transformed human fibroblasts.

A comparative study of chromosomal rearrangements occurring in 4 independent clones obtained from SV40-transformed cornea and skin human fibroblasts was performed. Rearrangements principally affect some constitutive heterochromatin and, to a lesser degree, telomeric regions. This results in multiple exchanges between a limited number of chromosome structures, i.e., in jumping translocations. Such rearrangements occur even at early passages and some of them give rise to clonal rearrangements that accumulate at late passages. This process is responsible for progressive modification of the karyotypes, principally characterized by deletion of a number of chromosome segments. Thus, clonal rearrangements are selected among many others not occurring at random. The selective pressure retaining clonal rearrangement seems to be similar for the 4 independent clones, since selection of the derivative chromosomes leads to the same imbalances, whatever the origin of the clone. This sequence of events recalls that of human solid tumors, since jumping rearrangements are generally observed in pre-malignant conditions or in low-grade malignancies, whereas clonal rearrangements leading to typical imbalances are detected in more advanced malignant tumors.

Cell Transformation, Neoplastic↗

PubMed1992

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↗

PubMed1991

Detection of translocations of 10p by non-radioactive in situ hybridization of VIM gene in SV40-transformed human cell lines.

SV40-transformed human fibroblasts exhibit characteristic chromosome imbalances, fairly well correlated with the activity of enzymes encoded by genes located on chromosome segments either in deficiency or in excess. However, a major discrepancy existed for the expression of vimentin gene (VIM), which was high, even though the map location of the gene (10p) was missing in many cell lines. An in situ hybridization technique using a biotinylated probe for the human VIM was applied to detect eventual cryptic translocations, as chromosome 10p is difficult to identify. In two cell lines (WI 98 and HEL1 HBLT) in which a loss of copy number of 10p was assumed after karyotyping, a signal for VIM was detected in unidentified short arms of derivative chromosomes. This exemplifies that in situ hybridization is a powerful complement to classical cytogenetics to detect rearrangements in highly rearranged karyotypes from transformed or cancerous cells. These results also strengthen the interpretation of the correlation between karyotypic and metabolic imbalances in transformed cells.

Cell Line, Transformed↗

PubMed1991

[Chromosome hyper-radiosensitivity in mice at the end of pregnancy].

Irradiation of mice with 2 Gy of gamma-rays at various times of pregnancy induces a threefold increase in the rate of chromosome breaks in spontaneously dividing bone marrow cells from the 16th to 19th days. This high sensitivity disappears shortly after delivery, and it is even possible that a hyposensitivity develops at this time. The causes of this phenomenon remain unknown, but since it occurs shortly after the high increase of oestrogen and progesterone hormones, a direct relationship may exist.

Animals↗

PubMed1988

SV40-transformed human fibroblasts exhibit a characteristic chromosomal pattern.

A karyotype study of seven SV40-transformed human fibroblast cell lines was performed using R-banding. Although large variations existed from line to line and, to a lesser degree, from cell to cell in a given line, many common features were found. The most characteristic were chromosome imbalances. Some of the chromosomes or chromosome segments present in excess were, in decreasing order of frequency, the early replicating X, 12q, 3q, 12p, 19, 1p, and 6p. Losses of other chromosomes and chromosome segments were also frequent and involved 11p, 2p, 6q, 10p, 18, 4q, 8p, 4p, 10q, and 16. These imbalances seemed to correlate with metabolic characteristics, previously described, such as low activities of catalase (11p), superoxide dismutase 2 (6q), and acid phosphatase (2p, 11p) and a high ratio of lactate dehydrogenase B (LDHB, 12p) activity to LDHA (11p) activity.

Cell Line↗

PubMedDate not supplied

Variations of chromosome radiation sensitivity in fetal and adult mice during gestation.

Mice were exposed to 2 Gy of gamma-rays at various days of pregnancy, and just before and after gestation. Chromosomes were analyzed 4 h after irradiation in spontaneously dividing hematopoietic cells from liver for fetuses and bone marrow for mothers. On average, there was significantly less chromosome damage in fetuses than in mothers. A very strong increase of chromosome breakage was observed in mothers at days 16-19 of gestation. This increase parallels that of gestation hormones, suggesting a direct relationship. The differences between fetuses and mothers in relation to gestation age result from the increase in the rate of chromatid and chromosome breaks but not of chromatid exchanges, which remained stable. This suggests that a DNA repair step involved in joining broken extremities is the cause. More experiments are needed to understand the origin of these variations of radiation sensitivity and the possible extrapolation of these observations to other species.

Animals↗