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Biomedical subjects

B Dutrillaux

Publications and source records attributed to B Dutrillaux.

At least 271 records · Page 15Linked to original sources

Existence of two distinct processes of chromosomal evolution in near-diploid colorectal tumors.

The comparison of all the karyotypes established in each of 18 near-diploid colorectal tumors made it possible to reconstruct a clonal evolution and to distinguish between early and late chromosomal aberrations. Because no abnormalities were observed in all tumors, and as even the most frequent changes, i.e., monosomy 17p and monosomy 18, may be present in mosaic, no chromosomal change can be regarded as a common primary event in the carcinogenetic process. However, the repeated occurrence of several changes favors the hypothesis of two karyotypic evolutionary processes. In most tumors, monosomy 17p and 18 were found, and the karyotypic evolution involved mainly several additional monosomies due to unbalanced rearrangements or losses that affect, by order of decreasing frequency, chromosomes 1p, 4, 14, 5q, 6q, 2p, and 11q, as well as gains of chromosomes 20, 8q, 13, 17q, and X. In this group of tumors, the mean number of chromosomes remains close to 46. In the other tumors, either only a monosomy 17p or a monosomy 18 was found and the karyotypic evolution involved essentially trisomies, resulting from gains with, by order of decreasing frequency, a preferential involvement of chromosomes 7, 8q, 13, 17q, 20, X, 2p, 5, and 16, the only additional recurrent deletion affecting chromosome 1p. In these tumors, the mean chromosome number is close to 51. Ten out of 11 polyploid sidelines emerged from monosomic-type tumors.

Chromosome Aberrations↗

Inactive X chromosome has the highest concentration of unmethylated Hha I sites.

A procedure enabling the highly sensitive detection of accessible restriction endonuclease sites on metaphase chromosomes is described. The procedure is based on the following: (i) a terminal deoxynucleotidyltransferase is used to add a biotinylated nucleotide (Bio-11-dUTP) tail to the 3' hydroxyl terminus generated by the action of a restriction enzyme and (ii) the biotinylated oligonucleotide is detected by a peroxidase-based immunocytochemical method. When used with the 5-methylcytosine-sensitive enzyme Hha I, it gives rise to a pattern close to R and T banding on autosomes. In addition, the staining of one X chromosome in females appears very unusual by its pattern and its strong intensity. This procedure, as applied on a case with a polysomy X chromosome, provides direct evidence of an overall hypomethylation of the inactive X chromosomes.

Cells, Cultured↗

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↗

Studies on the human chromosome 3 centromere with a newly cloned alphoid DNA probe.

Starting from a chromosome-specific DNA library, we have isolated a human chromosome-specific satellite DNA sequence. This sequence of 635 base pairs (bp) consists of 3.7 alpha DNA monomers of 170-171 bp. Under high stringency it hybridizes to the centromere of chromosome 3 in a region composed of 2,750 bp tandem repeats characterized by the regular spacing of Hind III and TaqI restriction enzyme recognition sites. It has diverged and undergone amplification after the human speciation. The amplification allows an easy monitoring of the chromosome 3 centromere by in situ hybridization with a nonradioactive probe.

Animals↗

Karyotype evolution of the human HBL-100 cell line and mapping of the integration site of SV40 DNA.

Cytogenetic analysis of the human HBL-100 cell line, that we have previously shown to harbour SV40 genetic information (Caron de Fromentel et al., 1985), reveals numerous chromosomal rearrangements as soon as the 30th in vitro passage. The karyotype is relatively stable during in vitro maintenance and even at late passages (approximately 70) when the cells have acquired the capacity to form tumors in nude mice. In all the somatic cell hybrids obtained after fusion of mouse 3T3-4E cells with HBL-100 cells, several human chromosomes are maintained and a derivative from chromosome 15-der(15)- is the most frequently observed. The der(15) marker is present in the HBL-100 cell line at every passage studied as well as in different cell lines derived from tumors induced by HBL-100 cells. The various hybrids, originally isolated for a transformed phenotype on the basis of their ability to grow in soft-agar, were all found to express the SV40 T-antigen. In situ hybridization of an SV40 DNA probe to chromosome spreads obtained from one of these hybrids shows that the integration site of the viral genome is located on the der(15) marker chromosome, at band 15q24. The possible cooperation of SV40 T-antigen with some other oncogene(s), required by human HBL-100 cells in order to express a malignant phenotype, is discussed.

Cell Line↗

[Recent data on the cytogenetics of colorectal adenocarcinoma].

A brief description of the results obtained by cytogenetic analyses of cancer cells from colorectal adenocarcinomas is reported. Two distinct patterns of chromosomal anomalies are observed. The major one, called "monosomic type", because many chromosomes losses exist, is characterised by the losses or deletions of the following chromosomes 18, 17 (short arm = p), 1p, 4, 14, 5 (long arm = q) and 21. It frequently evolves towards polyploidy, by duplication of all remaining chromosomes. The minor one, called "trisomic type", is characterised by the gain of several chromosomes: 7, 12, X, 5 and 8. The chromosomal anomalies observed seem to have no topological relationships with oncogenes, and other interpretations for their occurrence were investigated. The numerous and frequent deletions of some chromosomes, like 17p and 18, may indicate the involvement of recessive genes, like in the anti-oncogene system. In addition, it is observed that most deletions involve genes for "de novo" pathways whereas gains involve genes for salvage pathways of the synthesis of nucleotides. A correlated cytogenetic and enzymologic study was thus developed, and the first results show that the chromosomal pattern may well indicate the metabolic deviations. Monosomic type tumors have, on the average, a relatively low "de novo" and a high salvage pathways, and trisomic type tumors a high "de novo" and salvage pathways. Since chemotherapy is principally orientated against "de novo" pathways of the synthesis of nucleotides, these results may help to understand the difficulties of chemotherapy in colorectal cancers and perhaps to adapt it better.

Adenocarcinoma↗

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↗

Spontaneous chromosomal anomalies in lymphocytes from xeroderma pigmentosum. A study of ten patients.

A cytogenetic study of the lymphocytes from 6 classic and 4 variant forms of xeroderma pigmentosum is reported. This study performed on 978 R-banded metaphases shows that there is no specific chromosomal rearrangement in this disorder. In UDS-deficient forms, the rates of deletions, chromatid gaps and chromosome gaps are significantly increased. The preferential involvement of G-bands is discussed.

Chromosome Aberrations↗

Recurrent deletions of chromosomes 11q and 3p in anal canal carcinoma.

A cytogenetic study of 8 cases of anal canal cancer, including 1 cloacogenic and 7 squamous-cell carcinomas, was performed. All tumors exhibited chromosomal abnormalities. A rearrangement involving the long arm of chromosome 11 was seen in all instances, and, with the exception of the i (11q) found in one tumor, all the observed rearrangements resulted in a deletion of the distal segment. Rearrangements of chromosome 3, detected in 6 tumors, led to a deletion of the short arm in 5 cases. The association of these 2 deletions may characterize the anal canal carcinoma, the smallest common deleted segments being distal to 11q22 or q23 and 3p22.

Adult↗

Isoacentric and isocentric chromosomes originating after deletions of human chromosomes.

The analysis of a sample of 100 isoacentric (IA) and isocentric (IC) chromosomes, which had originated from spontaneous or radiation-induced deletions in human lymphocytes, is reported. IC and also IA have a strong tendency to be formed after breakage in juxtacentromeric heterochromatin. When euchromatic regions are involved, the breaks are not distributed at random since they frequently occur at places where juxtacentromeric heterochromatin exists in other primate species. It is assumed that intercalary structures conserving some of the properties of heterochromatin exists in human chromosomes in intercalary positions.

Chromosome Aberrations↗