Glucocorticoid induced lymphocytolysis

Various cells of lymphatic origin, most prominently immature thymocytes and certain leukaemia and lymphoma cells respond to high physiological or pharmacological doses of glucocorticoids by growth inhibition and cell lysis [8,12,17-25], In some cells the response is limited to the inhibition of cell proliferation, in others an initial phase of diminished growth with preferential accumulation of cells in the G, phase 

Lymphoid, cell variants with altered hormone responsiveness 

Despite the uncertainty in the mechanism of hormone-induced lymphocytolysis, cultured cells of mouse and human origin have been very useful for obtaining resistant cell variants. Mostly, three cell culture lines have been used S49.1 and WEHI-7 mouse lymphoma cells of thymic origin [43,44] and human CEM-C7 lym- 

The above mentioned cell lines can be cloned under appropriate conditions in soft agar. Upon addition of high concentrations of a potent glucocorticoid, for example, dexamethasone at 0.1-1 /rM concentrations the vast majority of S49.1 or CEM-7 cells die but a few cells form colonies. These clones are completely resistant to the cytolytic hormone effect. Resistance is a stable heritable trait which arises randomly in the cell population treatment with mutagens increases the rate at which resistant cells come up [20,53]. 

The same cloning procedure has also been used for obtaining cell variants of decreased sensitivity [54], In this case S49.1 subclones were isolated which grew in the presence of much lower concentrations, i.e., 10 nM dexamethasone. These variants turned out to contain significantly reduced levels of glucocorticoid receptors with unaltered affinity for the steroid. This observation suggests that receptors are not only a necessary requirement for hormone action but also play a quantitative role. A relationship between cellular receptor content and the extent of hormonal sensitivity has in fact been seen in a series of mouse lymphomas of independent origin [52]. 

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