Effects of X-irradiation and sodium butyrate on cell-cycle traverse on normal and radiosensitive lymphoblastoid cells.
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.
P J
PJ
Smith
C O
CO
Anderson
J V
JV
Watson
D001260:Ataxia Telangiectasia / Q000235:genetics / Q000473:pathology; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects*; D002455:Cell Division; D002472:Cell Transformation, Viral; D002843:Chromatin / Q000032:analysis; D004247:DNA / Q000032:analysis; D003703:Demecolcine / Q000494:pharmacology; D003851:Deoxyribonucleases / Q000378:metabolism; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D008214:Lymphocytes / Q000166:cytology*; D012313:RNA / Q000032:analysis; D012260:Ribonucleases / Q000378:metabolism; D013997:Time Factors
D002087:Butyrates; D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D020148:Butyric Acid; D012313:RNA; D004247:DNA; D003851:Deoxyribonucleases; D012260:Ribonucleases; D003703:Demecolcine