Dexamethasone induces irreversible G1 arrest and death of a human lymphoid cell line

✍ Scribed by Jeffrey M. Harmon; Michael R. Norman; Betty Jo Fowlkes; E. Brad Thompson

• Publisher: John Wiley and Sons
• Year: 1979
• Tongue: English
• Weight: 832 KB
• Volume: 98
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1040980203

✦ Synopsis

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dexamethasone results in inhibition of growth and rapid loss of cell viability after a delay of approximately 18 to 24 hours. Analysis of dexamethasonetreated cells by flow-microfluorometry showed that they were arrested in the GI phase of the cell cycle. Loss of cell viability began at the same time as G, accumulation was first detectable, and 20% of all cells were found to be blocked in G, at this time suggesting that loss of viability and GI arrest were coincident events. Half-maximal and maximal effects on both viability and GI arrest after 48 hours in steroid were nearly identical with respect to steroid concentration and corresponded to half-maximal and full occupancy of glucocorticoid specific receptor by hormone, consistent with a glucocorticoid receptor mediated mechanism for both phenomena. Most non-viable cells were arrested in G1, and accumulation of cells in G1 was irreversible; removal of steroid in the presence of colcemid did not result in a decreased fraction of G, cells. Furthermore, dexamethasone treatment did not protect cells against the effects of 33258 Hoechstamplified killing of bromodeoxyuridine substituted cells exposed to light. These results show that dexamethasone arrests these leukemic cells in GI and strongly suggest that dexamethasone-treated cells are killed upon entry into GI.

Growth of a human leukemic T-cell line (CEM C7) in '