Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer incidence was measured retrospectively in 574 close blood relatives of white ataxia-telangiectasia (A-T) patients and 213 spouse controls in 44 previously unreported families. The cancer incidence rate in the adult blood relatives was significantly elevated over the rate in the spouse controls (rate ratio = 3.9, p less than 0.01). For heterozygous carriers of the A-T gene, the relative risk of cancer was estimated to be 6.1 (p less than 0.005) as compared with nonheterozygotes. The most frequent cancer site in the blood relatives was the female breast, with nine cancers observed. These findings provide further support for the hypothesis that heterozygotes for the A-T gene are predisposed to cancer.
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PMID:Cancers in 44 families with ataxia-telangiectasia. 225 79

Patients who are homozygous for ataxia-telangiectasia (AT) have an exceptionally high incidence of cancer. Heterozygous individuals for the disease have been reported to be at an increased risk of cancer, particularly breast cancer in female carriers. We have analyzed eight Norwegian families with AT for cancer incidence in the parents, in the parents' sibs, grandparents, and grandparents' sibs. Two of the obligate heterozygote females have had premenopausal breast cancer. This incidence is significantly higher than expected for that group. No increase in the cancer incidence was observed in the parents' sibs, the grandparents, or the grandparents' sibs. Since the incidence of AT is low, data from many sources have to be combined to allow any conclusion.
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PMID:Breast cancer and other cancers in Norwegian families with ataxia-telangiectasia. 226 81

Induction and rejoining of DNA single-strand breaks (ssb) and double-strand breaks (dsb) after gamma-irradiation were measured, respectively, by alkaline and neutral sucrose gradient sedimentation methods. The radiosensitive mutants irs1, irs2, and irs3 showed no significant difference from wild-type V79 hamster cells in ability to rejoin either ssb or dsb, while the previously-described xrs-1 mutant showed the expected defect in rejoining dsb. The resistance of DNA synthesis to gamma-irradiation was measured in the 3 irs mutants and, for comparative purposes, in transformed human cell lines from normal and ataxia-telangiectasia (A-T) individuals. The irs2 mutant was found to be very similar in response to the A-T lines, showing a marked decrease in inhibition of DNA synthesis, compared to V79 cells, in both time-course and dose-response experiments. However, irs1 also had some decrease in inhibition at the higher doses used, while irs3 was similar to the wild-type V79 cells. Both irs1 and irs2 were found to be considerably more sensitive to the DNA topoisomerase I-inhibitor camptothecin, while irs3 was only slightly more sensitive than the parent V79 line. These data place the irs mutants in a similar category of radiosensitive phenotype to A-T cells, but we view this as only the beginning of a useful classification of this type of mutant. The irs2 mutant has the strongest links to A-T cells, through its sensitivity profile to DNA-damaging agents and radioresistant DNA synthesis, but irs1 in particular has other similarities to A-T.
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PMID:DNA-break repair, radioresistance of DNA synthesis, and camptothecin sensitivity in the radiation-sensitive irs mutants: comparisons to ataxia-telangiectasia cells. 230 92

Two breakpoints within chromosome 11q23 were characterized with 29 DNA probes to establish a physical map of the region. This region is notable in that it contains at least 14 functional genes which are also syntenic in the mouse (chromosome 9). Chromosome 11q23 includes these markers: STMY, CLG, NCAM, DRD2, APOA1, APOC3, APOA4, CD3E, CD3D, CD3G, PBGD, THY1, ets-1, and cbl-2. The two breakpoints, herein called "X;11" and "4;11," defined a region of approximately 8 cM containing the APO and CD3 complexes as well as the polymorphic marker D11S29. DRD2 localized centromeric to the X;11 breakpoint despite evidence for close genetic linkage to D11S29, suggesting that DRD2 lies close to the X;11 breakpoint. THY1, PBGD, and cbl-2 localized telomeric to the 4;11 breakpoint and thus to the [D11S29--APO--CD3] grouping as well. The physical map helps to correlate the cytogenetic and linkage maps of this region. It also suggests that the human 11q23 syntenic grouping is inverted with respect to its murine counterpart. Based on this physical map and on our primary linkage map of the 11q23 region, we are able to confirm a preliminary localization of the gene for ataxia-telangiectasia group A (ATA) to a region centromeric to the interval defined by D11S144 (pYNB3.12) and THY1.
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PMID:Physical mapping of the human chromosome 11q23 region containing the ataxia-telangiectasia locus. 233 77

An assay for ataxia-telangiectasia (A-T) heterozygotes, i.e., healthy carriers of the A-T gene(s), requiring only a small sample (3.5 mL) of peripheral blood, is described. Frequencies of chromatid aberrations in phytohemagglutinin-stimulated blood lymphocytes collected by demecolcine from 0.5 hour to 1.5 hours after x irradiation with 58 roentgens were twofold to threefold higher in A-T heterozygotes than in clinically normal controls and twofold to three-fold higher in A-T patients (homozygotes) than in A-T gene carriers. The persistence of chromatid breaks and gaps in lymphocytes following radiation-induced DNA damage during G2 suggests a deficiency or deficiencies in DNA repair that may be the defect at the molecular level that results in the enhanced radiosensitivity and cancer proneness characterizing A-T gene carriers and patients.
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PMID:Enhanced chromatid damage in blood lymphocytes after G2 phase x irradiation, a marker of the ataxia-telangiectasia gene. 234 70

A technique for nonradioactive in situ hybridization on human metaphase chromosomes has been developed to localize human cosmid clones. The simple procedure using two fluorescent dyes (fluorescein and propidium iodide) allows the simultaneous identification of chromosomal R-bands and hybridization signal in a single screening of the slides. This technique has been used for rapid correlation of the genetic and physical map of chromosome 11q13-qter in the region of genes responsible for ataxia-telangiectasia and tuberous sclerosis.
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PMID:Simultaneous localization of cosmids and chromosome R-banding by fluorescence microscopy: application to regional mapping of human chromosome 11. 239 67

A 14-year-old boy received standard induction chemotherapy for acute lymphoblastic leukaemia followed by standard dose cranial radiation prophylaxis (18 Gy). Severe chemosensitivity and acute radiation reactions occurred and he died at 8 months from late radiation damage. In vitro radiobiological studies of the boy's fibroblasts in culture demonstrated an enhanced radiosensitivity indistinguishable from ataxia-telangiectasia (A-T) cells. However, unlike A-T cells, DNA synthesis following irradiation was inhibited in a normal manner. This patient represents yet another example of extreme radiosensitivity, and the possibility of clinical prediction in the future is discussed.
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PMID:An instance of clinical radiation morbidity and cellular radiosensitivity, not associated with ataxia-telangiectasia. 240 Aug 79

In the present study we examined cells from several patients clinically diagnosed as having ataxia-telangiectasia (AT), for the capacity of their cells to inhibit DNA synthesis following exposure to gamma irradiation, and for the rate of spontaneous or bleomycin-induced chromosomal aberrations. Cells from two patients showed normal inhibition of DNA synthesis and levels of induced chromosomal aberrations intermediate between normal and AT cells. These two patients had only minimal immunologic impairment. These findings appear to define one distinct subset of AT.
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PMID:Variant of ataxia-telangiectasia with low-level radiosensitivity. 241 Mar 49

In agreement with our earlier observation (Scott and Zampetti-Bosseler, 1982) on X-irradiated normal and ataxia-telangiectasia (A-T) fibroblasts, we now report that after bleomycin or neocarzinostatin treatment also, A-T cells exhibit less G2 delay than normal cells. We confirm that A-T cells sustain more chromosome damage and lethality than normal cells after bleomycin. These observations support the hypothesis (Painter and Young, 1980) that A-T cells are defective in the recognition of certain lesions which normally lead to delays in progression through the cell cycle, during which they are repaired, and which, if unrepaired, lead to cell-lethal chromosome damage. However, we find that after bleomycin, as opposed to X-rays, the contribution of this type of lesion to cell death is minimal. The predominant lesions leading to cell death after bleomycin are not manifested at chromosome aberrations and do not lead to G2 delay or DNA-synthesis inhibition. A-T cells are defective in the recognition and/or repair of both types of lesion.
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PMID:The response of normal and ataxia-telangiectasia cells to bleomycin: relationships between chromosome damage, cell cycle delay and cell killing. 241 Jul 88

We have used a multi-parameter flow-cytometric technique to analyse changes in cell-cycle phase distribution (early and late G1, S and G2+M phases) for normal and X-ray-sensitive (ataxia-telangiectasia, A-T) lymphoblastoid cells exposed to X-irradiation and sodium butyrate (either alone or in combination). Sodium butyrate, an inhibitor of histone deacetylase, is a useful pharmacological tool for determining the proposed role of a histone acetylation-based chromatin surveillance system in controlling cell-cycle responses to DNA damage. We report that X-irradiated A-T cells (acute doses up to 1.5 Gy) demonstrate deficiencies in the capacity to traverse G1 and G2+M phases, although we can find no evidence of the specific involvement of a sodium butyrate-sensitive process in normal cells or abnormalities in the responses of A-T cells to the drug. We conclude that abnormal cellular control of G1 transition in A-T may be the basis of disturbed cellular differentiation in vivo, particularly in non-proliferating tissues under conditions of accumulated environmental or spontaneous DNA damage.
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PMID:Effects of X-irradiation and sodium butyrate on cell-cycle traverse on normal and radiosensitive lymphoblastoid cells. 241 68


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