Breakage of DNA and alterations in folded genomes by inducers of differentiation in Friend erythroleukemic cells.

摘要: Abstract Friend erythroleukemia cells are induced to differentiate when treated with dimethyl sulfoxide (DMSO) and a number of other structurally unrelated agents, some which also known alter the structure DNA. In order determine whether DMSO was responsible for DNA damage, properties [ 3 H]thymidine-labeled from untreated were compared on alkaline sucrose gradients. Criteria degradation were: ( ) an increase in radioactivity slowly sedimenting approximately 17S DNA, b decrease amount heavy, major 140S peak, c shift position heavy peak lower S value. Increasing damage found increasing doses DMSO. The earliest change, detected at 3.5 hr, peak. Therefore, breaks prior stimulation globin messenger RNA hemoglobin synthesis. Other potent inducers, such as butyrate, caused similar degradation. Agents that cause (X-ray, bleomycin, UV) stimulate partial erythrodifferentiation these cells. “Folded genomes” prepared 24-hr control DMSO-treated cultures labeled either H]- or 14 C]thymidine, respectively. Cosedimentation folded genomes revealed 10% value samples control. Reverse labeling, contained C H, gave results. These changes consistent accumulation single-stranded nicks genomes. scission may be early step differentiation.