Cell cycle dependent DNA break increase in ataxia telangiectasia lymphoblasts after radiation exposure. 2001

B Humar, and H Müller, and R J Scott
Research Group Human Genetics, Department of Research, University Clinics, CH-4031 Basel, Switzerland.

The most striking feature of ataxia telangiectasia (AT) cells is their profound sensitivity to ionising radiation. A deficiency in the rejoining of radiation induced DNA breaks has been suggested to be responsible for AT radiosensitivity; however, the existing literature is controversial. A subpopulation, which is present in irradiated AT lymphoblasts, but rarely in controls, has been reported previously. The cells that make up this subpopulation harbour highly fragmented DNA and are responsible for the overall increase in DNA breaks soon after irradiation in AT lymphoblasts. This study examines the influence of the cell cycle on the highly damaged subpopulation. The frequency of highly damaged cells was highest when AT lymphoblasts were irradiated during the G2/M phase. In contrast, AT lymphoblasts irradiated during the G0/G1 phase displayed a frequency similar to control cells. Thus, only G2/M and to some extent S phase cells contribute to an increased DNA break number in AT lymphoblasts early after irradiation. These findings might explain several inconsistencies reported in the literature.

UI MeSH Term Description Entries
D002453 Cell Cycle The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE. Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D001260 Ataxia Telangiectasia An autosomal recessive inherited disorder characterized by choreoathetosis beginning in childhood, progressive CEREBELLAR ATAXIA; TELANGIECTASIS of CONJUNCTIVA and SKIN; DYSARTHRIA; B- and T-cell immunodeficiency, and RADIOSENSITIVITY to IONIZING RADIATION. Affected individuals are prone to recurrent sinobronchopulmonary infections, lymphoreticular neoplasms, and other malignancies. Serum ALPHA-FETOPROTEINS are usually elevated. (Menkes, Textbook of Child Neurology, 5th ed, p688) The gene for this disorder (ATM) encodes a cell cycle checkpoint protein kinase and has been mapped to chromosome 11 (11q22-q23). Louis-Bar Syndrome,Ataxia Telangiectasia Syndrome,Ataxia-Telangiectasia,Telangiectasia, Cerebello-Oculocutaneous,Louis Bar Syndrome,Syndrome, Ataxia Telangiectasia,Syndrome, Louis-Bar
D001402 B-Lymphocytes Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B-Cells, Lymphocyte,B-Lymphocyte,Bursa-Dependent Lymphocytes,B Cells, Lymphocyte,B Lymphocyte,B Lymphocytes,B-Cell, Lymphocyte,Bursa Dependent Lymphocytes,Bursa-Dependent Lymphocyte,Lymphocyte B-Cell,Lymphocyte B-Cells,Lymphocyte, Bursa-Dependent,Lymphocytes, Bursa-Dependent
D053938 DNA Fragmentation Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS. DNA Degradation, Apoptotic,Apoptotic DNA Degradation,Fragmentation, DNA
D020552 Comet Assay A genotoxicological technique for measuring DNA damage in an individual cell using single-cell gel electrophoresis. Cell DNA fragments assume a "comet with tail" formation on electrophoresis and are detected with an image analysis system. Alkaline assay conditions facilitate sensitive detection of single-strand damage. Alkaline Comet Assay,Alkaline Single-Cell Gel Electrophoresis Assay,Electrophoresis, Gel, Single-Cell,Gel Electrophoresis, Single-Cell,Alkaline Comet Assays,Alkaline Single Cell Gel Electrophoresis Assay,Assay, Alkaline Comet,Assay, Comet,Assays, Alkaline Comet,Assays, Comet,Comet Assay, Alkaline,Comet Assays,Comet Assays, Alkaline,Electrophoreses, Single-Cell Gel,Electrophoresis, Single-Cell Gel,Gel Electrophoreses, Single-Cell,Gel Electrophoresis, Single Cell,Single-Cell Gel Electrophoreses,Single-Cell Gel Electrophoresis

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