Cell kinetic disturbances induced by treatment of human diploid fibroblasts with 5-azacytidine indicate a major role for DNA methylation in the regulation of the chromosome cycle |
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Authors: | Martin Poot Julia Koehler Peter S. Rabinovitch Holger Hoehn Jean H. Priest |
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Affiliation: | (1) Institut für Humangenetik der Universität, Koellikerstrasse 2, D-8700 Würzburg, Germany;(2) Department of Pathology, SM 30, University of Washington, 98195 Seattle, WA, USA;(3) Department of Pediatrics, Division of Medical Genetics, Emory University, 30030 Atlanta, GA, USA |
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Abstract: | Summary BrdU-Hoechst flow cytometry was used to investigate the effects of DNA hypomethylation, induced by treatment with 5-azacytidine (5AC), on cell proliferation. When human fibroblast-like cells derived from skin and amniotic fluid were exposed to 5AC during three successive cell cycles, their clone-forming ability was diminished after removal of the drug. Treated cells were rendered quiescent by culture with low serum in the absence of the drug. Upon serum stimulation, they showed a diminished fraction of proliferating cells, which exhibited a prolonged transit through the S and G2 phase of the cell cycle, and a permanent arrest within the G2 compartment. This pattern of disturbed cell proliferation may in part explain the changes in replication banding pattern reported in the literature. Cytogenetic analysis of 5AC-treated cells revealed numerous endomitoses and tetraploid metaphases indicating a disturbed chromosome cycle in association with these cell kinetic perturbations. |
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