title: Relationship between a chromatin anomaly in ataxia-telangiectasia cells and enhanced sensitivity to DNA damage.
abstract: The cellular basis for the enhanced sensitivity to ionising radiation and some DNA damaging chemicals in ataxia-telangiectasia (AT) cells is not clearly understood. Abnormalities in cell-cycle traverse, chromosome stability and DNA synthesis patterns have suggested that a chromatin associated defect may be the primary lesion in AT. This study involves an attempt to define such an anomaly by the use of a vital DNA specific bis-benzimidazole dye (Hoechst 33342) and deoxyribonuclease II as probes for chromatin organisation in intact and permeabilised human cells respectively. Despite similar DNA binding characteristics (determined by flow cytometry) of Ho33342 in normal and AT transformed fibroblasts, the AT cells show: (i) enhanced cell killing and increased accumulation of cells in G2 phase of the cell-cycle [both biological responses being relatively resistant in AT cells to modification by an inhibitor of poly (ADP ribosyl)ation], (ii) no resistance of de novo DNA synthesis to Ho33342-induced inhibition, (iii) elevated levels of slow-rejoining ligand-induced DNA strand-breaks, and (iv) enhanced expression of chromatin regions accessible to an exogenously supplied endonuclease. The results are interpreted on the basis that a chromatin anomaly of enhanced nuclease susceptibility, involving a minor fraction of the genome, may be a controlling factor in the expression of the various in vivo and in vitro characteristics of AT cells.
mesh_terms: D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000378:metabolism; D001549:Benzamides / Q000633:toxicity; D001562:Benzimidazoles / Q000633:toxicity; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002843:Chromatin / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D006801:Humans
chemical_list: D001549:Benzamides; D001562:Benzimidazoles; D002843:Chromatin; C025160:3-aminobenzamide; D004247:DNA; C017807:bisbenzimide ethoxide trihydrochloride