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)

Lower cell density was found in cultures of ataxia telangiectasia lymphocytes as compared to control lymphocyte cultures. This fits with the earlier observations of decreased incorporation of 3H-Thymidine into lymphocytes of ataxia telangiectasia (AT) patients. However, the finding that there was no significant difference in proliferation rate index between AT and control cultures was unexpected. This may indicate that both cell count and measurements of thymidine incorporation in lymphocyte cultures characterize cell populations distinct from that of proliferating cells.
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PMID:Unaltered cell proliferation rate of the ataxia telangiectasia lymphocytes dividing in vitro. 186 35

We investigated the dominant/recessive nature of the XR-1 mutant locus in intraspecies Chinese hamster ovary (CHO) hybrids and interspecies hybrids with human cell lines that possess different radioresistances. The XR-1 cell is abnormally sensitive to killing by gamma rays in the G1 phase of the cell cycle, while late-S-phase cells have wild-type resistance. [3H]Thymidine selection was used to eliminate the resistant S-phase population. In both intraspecies and interspecies hybrids, the XR-1 mutation is recessive to the wild-type cell and is not influenced by differences in chromosome ploidy. Analysis of hybrids between human ataxia telangiectasia fibroblasts AT5BI and XR-1 cells revealed that they possess different genetic defects as they complemented each other in three of four hybrids tested. These data suggest that the XR-1 locus is evolutionarily conserved between hamster and human cells.
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PMID:Genetic analysis of XR-1 mutation in hamster and human hybrids. 291 63

An approach of general applicability to mammalian radiosensitive mutants has been used in the analysis of gene dosage and complementation in ataxia telangiectasia (A-T). Thymidine residues in DNA of one parental lymphoblastoid cell line were substituted with bromodeoxyuridine before fusion with a second parental cell line, to allow differential staining of the two sets of chromosomes. Following gamma-irradiation, induced chromosome aberrations were scored in diploid and homokaryon cells from each parental line as well as in heterokaryons. Four complementation groups were ascertained among 7 A-T cell lines. Analysis of heterokaryons formed between appropriate combinations of normal, A-T homozygote and A-T heterozygote cells, gave a quantitative measure of gene dosage and demonstrated increasing radiosensitivity with increasing numbers of A-T alleles.
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PMID:Gene dosage and complementation analysis of ataxia telangiectasia lymphoblastoid cell lines assayed by induced chromosome aberrations. 650 56

Little work has been done on the mechanism of low dose hyper-radiosensitivity (HRS) and later appeared radioresistance (termed induced radioresistance (IRR)) after irradiation with medium and high linear energy transfer (LET) particles. The aim of this study was to find out whether ATR pathway is involved in the mechanism of HRS induced by high LET radiation. GM0639 cells and two ATM deficient/mutant cells, AT5BIVA and AT2KY were irradiated by carbon ion beam. Thymidine block technique was developed to enrich the G2-phase population. Radiation induced early G2/M checkpoint was quantitatively assess with dual-parameter flow cytometry by detecting the cells positive for phospho-histone H3. The involvement of ATR pathway in HRS/IRR response was detected with pretreatment of specific inhibitors prior to carbon ion beam. The link between the early G2/M checkpoint and HRS/IRR under carbon ion beam was first confirmed in GM0639 cells, through the enrichment of cell population in G2-phase or with Aurora kinase inhibitor that attenuates the transition from G2 to M phase. Interestingly, the early G2/M arrest could still be observed in ATM deficient/mutant cells with an effect of ATR signaling, which was discovered to function in an LET-dependent manner, even as low as 0.2Gy for carbon ion radiation. The involvement of ATR pathway in heavy particles induced HRS/IRR was determined with the specific ATR inhibitor in GM0639 cells, which affected the HRS/IRR occurrence similarly as ATM inhibitor. These data demonstrate that ATR pathway may cooperate with ATM in the mechanism of low dose hypersensitivity induced by carbon ion beam.
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PMID:ATR signaling cooperates with ATM in the mechanism of low dose hypersensitivity induced by carbon ion beam. 2624 17