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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytogenetic damage in cells cultured from normal individuals and patients with ataxia telangiectasia (A-T) and xeroderma pigmentosum (XP) was induced by the chemotherapeutic antibiotics neocarzinostatin (NCS), tallysomycin (TLM) and bleomycin (BLM). Chromosomal breakage was specifically elevated in A-T cells when compared to the other genotypes tested. Similar results were not observed with the clastogens mitomycin C (MMC) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as all cells responded similarly. All 5 chemical agents caused a marked suppression of de novo DNA synthesis in normal and XP long-term lymphoid cell lines while the A-T cells seemed resistant to this effect of NCS, TLM and BLM.
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PMID:Increased clastogenicity and decreased inhibition of DNA synthesis by neocarzinostatin and tallysomycin in ataxia telangiectasia lymphoid cells. 618 42

Peripheral blood leukocytes (PBL) isolated from five patients with ataxia telangiectasia (AT) proved more difficult to transform following addition of exogenous Epstein-Barr virus than PBL isolated from AT heterozygotes or normal adults. PBL isolated from one AT patient transformed within the range expected for normal PBL. Once established in culture, the resulting lymphoblastoid cell lines (LCLs) were immortal and, though they grew slower than normal control LCLs, provided useful material for studying cellular phenotypes associated with AT lymphoid cell lines. All the resulting LCLs established from ataxia were more sensitive to X-irradiation than were LCLs established from controls as measured by colony formation in microtiter plates. Furthermore, X-ray-induced inhibition of semiconservative DNA synthesis in ataxia LCLs was less than that seen in normal LCLs. These results are in agreement with those obtained using cultured AT fibroblasts, indicating that in vitro transformation by exogenously added Epstein-Barr virus does not alter the phenotype of the ataxia cell as measured by these two parameters. However, no deficiency in X-ray-induced excision repair of DNA was demonstrable in LCLs established from four AT patients. Nor was there a deficiency in AT LCL host cell reactivation of herpes simplex virus X-irradiated under anoxic conditions. Taken together, these data point toward a defect in ataxia lymphoblasts other than repair enzyme(s) per se, one possibly associated with chromosomal structure, function, or modification.
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PMID:Transformation and repair replication in lymphocytes from ataxia telangiectasia. 630 13

We have studied the in vitro malignant progression of human lymphoid cells by the combined effect of genetic, viral and mutagenic factors. A lymphoblastoid cell line immortalized by Epstein-Barr virus was used; it was derived from a patient suffering from ataxia-telangiectasia, a genetic disease linked to a deficiency in DNA repair. Cells were treated by sub-toxic doses of two potent mutagens (carcinogens), NQO (4-nitroquinolein-oxid) and R 7 000 (2-nitro-7-methoxy-naphto-furan). The treated cells showed an increased ability to form colonies in soft agarose, among which some compact colonies appeared, different from the diffuse colonies formed by untreated control cells. Sub-clones derived from these compact colonies differ also from the original cells by their behavior in liquid culture medium, by their increased tumorigenicity in Nude Mice and by their capacity to form nodules on Chicken chorioallantoic membrane. Some of the sub-clones produce non-regressing large tumors in Nude Mice with a cell inoculum lower than that required for Burkitt lymphoma cells while being less invasive than the latter. However, by their morphology, the malignant cells of the sub-clones remain similar to the original lymphoblastoid cells. Thus, such a malignant progression obtained in vitro cannot be considered as identical to that which leads to Burkitt lymphoma in African children.
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PMID:[Supertransformation of a human lymphoblastoid cell line by chemical carcinogens]. 630 29

An enzyme that enhances the activity of DNA polymerase I (EC 2.7.7.7) for gamma-irradiated calf thymus DNA was demonstrated in cellular extracts of normal human fibroblasts and lymphoid-cell lines. This enzyme was found to be deficient in all cellular extracts of fibroblasts and lymphoid-cell lines examined from patients with the autosomal recessive disease ataxia telangiectasia. The activity in cellular extracts from normal fibroblasts was removed when heated to 100 degrees C for 2 min or when the assay was performed at 4 degrees C. No significant deficiency in primer-activating enzyme activity was observed in cell-free extracts of lymphoid lines from patients with xeroderma pigmentosum, Huntington's chorea or neurofibromatosis, or from an ataxia telangiectasia heterozygote.
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PMID:An enzyme activity in normal and ataxia telangiectasia cell lines which is involved in the repair of gamma-irradiation-induced DNA damage. 645 Dec 16

Long-term lymphoid cell lines (LCL) derived from normal individuals, patients with ataxia telangiectasia (A-T), xeroderma pigmentosum (XP), and Fanconi anemia (FA) were exposed to various concentrations of 11 chemical clastogens. The agents were chosen to represent a variety of suggested modes of action. In contrast to all other genotypes, the FA lines demonstrated significant rates of spontaneous chromosomal breakage and showed hypersensitivity to all of the clastogens employed. Variability among lines within a genotype suggested individual responses to specific agents. Computation of "corrected values" to address the problem of baseline disparity removed some of the significant differences between the FA and other lines. Nonetheless, following correction, the FA genotype was still delineated by clastogens which are not DNA cross-linkers. The A-T lines were specifically identified by the induction of chromosome damage by bleomycin and neocarzinostatin.
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PMID:Chemical clastogenicity in lymphoid cell lines of chromosomal instability syndromes. 662 24

The induction of partial maturation in an in vitro derived Abelson virus-transformed murine lymphoid cell subline (ABC-1/AT1) is described. Pre-B (cytoplasmic, mu chain-positive) lymphocytes were induced from presumptive B cell precursors by prostaglandin E1, butyric acid, lipopolysaccharide and interferon. Maturation was independent of alterations in cellular growth rate and could be achieved in the absence of cell division. The AT1 subline was found to be restricted to the expression of a single light chain type (lambda) indicating a possible B cell lineage-committed precursor as the target for viral transformation.
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PMID:Partial maturation and light chain restriction of Abelson virus-transformed B cell precursors. 678 33

Lymphoblastoid cell lines (LCLs) established from chromosomal breakage syndromes or related genetic disorders have been used to study the effects of mutagens on human lymphoid cells. The disorders studied include xeroderma pigmentosum, ataxia telangiectasia, Fanconi's anemia, Bloom's syndrome and Cockayne's syndrome. Three approaches were used to assess the cells' ability to cope with a particular mutagen: (1) assaying recovery of DNA synthetic capabilities as measured by [3H]thymidine (dT) incorporation; (2) measurements of classical excision DNA repair by isopyknic sedimentation of DNA density labeled with 5-bromo-2-deoxyuridine (BrdU); (3) determining cell survival by colony formation in microtiter plates. LCLs established from xeroderma pigmentosum showed increased sensitivities to ultraviolet (354 nm) light and N-acetoxy-2-acetylaminofluorene (AAAF) as determined by DNA synthesis or colony formation and had diminished levels of excision-repair. Cockayne's syndrome LCLs, on the other hand, had increased sensitivities to ultraviolet (UV) light, AAAF and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) while showing near normal levels of DNA-repair after treatment with each agent. An LCL established from ataxia telangiectasia had decreased DNA repair synthesis and defective colony-forming ability following treatment with MNNG. LCLs, in addition to ease of establishment, appear likely to provide useful material for the study of DNA repair replication and its relationship to carcinogenesis.
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PMID:DNA repair in lymphoblastoid cell lines established from human genetic disorders. 743 93

The murine severe combined immune deficiency mutation (scid) is characterized by a lack of B- and T-lymphoid cells due to a defect in lymphoid V(D)J recombination. Moreover, defective rejoining of DNA double-strand breaks (dsb) in scid cells also results in a marked increase in sensitivity to ionizing radiation. Recently, the putative human homologue of the murine scid gene locus, HYRC1, was assigned to human chromosome 8q11, based on the radiation sensitivity of scid cells as compared to scid:human cell hybrids carrying portions of human chromosome 8. Given the precedent (e.g., ataxia-telangiectasia) for genes other than the affected one being able to complement radiation defects, we were interested in determining if the V(D)J recombination defect was also corrected by the HYRC1 locus. The V(D)J recombination analysis using extrachromosomal DNA substrates in control scid cells (SC3VA2) versus complemented cells (RD13B2) indicates that the radiation sensitivity-complemented cells (RD13B2) are also fully complemented for the V(D)J recombination reaction, whereas the control (uncomplemented) cells (SC3VA2) fail to carry out V(D)J recombination normally. Slightly over 60% of the radiation-induced dsb are rejoined even in scid cells, and this alternative pathway is temperature sensitive. Only the remaining 30-35% of dsb require the introduction of the HYRC1 locus, and this pathway is not temperature sensitive. This merely partial contribution of the scid factor to the repair process suggests the presence of another pathway of dsb repair. Our results indicate that the HYRC1 locus, assigned to human chromosome 8q11, encodes the scid factor, which is involved in all V(D)J recombination coding joint formation and in 30-35% of dsb repair by the temperature-resistant pathway.
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PMID:The scid factor on human chromosome 8 restores V(D)J recombination in addition to double-strand break repair. 771 87

Autopsy findings for two patients with the Nijmegen breakage syndrome (NBS) are presented. This syndrome has the same type of immunologic and cytogenetic abnormalities as ataxia telangiectasia (AT). In NBS, however, microcephaly is found and progressive cerebellar ataxia and oculocutaneous telangiectasia are lacking. We demonstrate a clear neuropathologic difference between these two syndromes, as the diffuse cortical cerebellar degeneration characteristic of AT was absent in NBS. In the thymus the histologic picture was suggestive of simple dysplasia. Lymphoid tissues were slightly atrophic but otherwise structurally normal. In one of the two presented cases an extranodal diffuse large cell malignant non-Hodgkin lymphoma of B cell immunoblastic type was found in Waldeyer's ring, in the small and large intestines, and in the brain, whose sequelae had caused death. Six of the 19 patients known with certainty to have this syndrome have developed lymphoid malignancy, which indicates that these patients are prone to develop malignancies.
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PMID:Postmortem findings in the Nijmegen breakage syndrome. 780 77

The murine severe combined immunodeficient mutation (scid) is characterized by a lack of both B and T cells, due to a defect in lymphoid variable-(diversity)-joining (V(D)J) rearrangement. Scid cells are highly sensitive to both radiation-induced killing and chromosomal aberrations. Significantly reduced D0 and n values were demonstrated in scid cells and were similar to ataxia-telangiectasia (AT) cells (a unique human disease conferring whole body radiosensitivity). However, the kinetics of DNA synthesis after irradiation were different between the two cell types. In contrast with the radioresistant DNA synthesis of AT cells, DNA synthesis of scid cells was markedly inhibited after irradiation. The existence of different mutations was also supported by evidence of complementation in somatic cell hybrids between scid cells and AT cells. Our results indicate that the radiobiological character of scid is similar to AT but is presumably caused by different mechanisms.
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PMID:Murine scid cells complement ataxia-telangiectasia cells and show a normal post-irradiation response of DNA synthesis. 810 Feb 59


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