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Dexamethasone induces irreversible G 1 arrest and death of a human lymphoid cell line
Author(s) -
Harmon Jeffrey M.,
Norman Michael R.,
Fowlkes Betty Jo,
Thompson E. Brad
Publication year - 1979
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1040980203
Subject(s) - dexamethasone , viability assay , glucocorticoid receptor , cell culture , colcemid , glucocorticoid , steroid hormone , bromodeoxyuridine , endocrinology , cell cycle , biology , programmed cell death , steroid , flow cytometry , medicine , chemistry , cell growth , cell , microbiology and biotechnology , apoptosis , hormone , biochemistry , genetics
Growth of a human leukemic T‐cell line (CEM C7) in 10 −6 M 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 G 1 phase of the cell cycle. Loss of cell viability began at the same time as G 1 accumulation was first detectable, and 20% of all cells were found to be blocked in G 1 at this time suggesting that loss of viability and G 1 arrest were coincident events. Half‐maximal and maximal effects on both viability and G 1 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 G 1 , and accumulation of cells in G 1 was irreversible; removal of steroid in the presence of colcemid did not result in a decreased fraction of G 1 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 G 1 and strongly suggest that dexamethasone‐treated cells are killed upon entry into G 1 .