Abstract
Thirteen independently derived murine thymic lymphosarcoma lines were assayed for various aspects of sensitivity to glucocorticoid-induced cytolysis. All tumor lines were sensitive to cytolysis, as evidenced by profound tumor regression after pharmacologic doses of cortisol. All tumor lines contained about 20,000 high-affinity, dexamethasone binding sites/cell. Between 55 and 88% of these presumptive receptor sites underwent nuclear translocation during a 30-minute incubation at 37 degrees C. Dissociation constants (Kd) for the dexamethasone-receptor complex were between 1.5 and 3.6 nM in all cases. Kd for the triamcinolone acetonide-receptor complex were determined for a few tumor lines and were between 0.5 and 0.9 nM. Cytolysis-resistant subpopulations were selected by prolonged glucocorticoid treatment of BALB/c pi mice bearing tumors from seven of the lymphosarcoma lines. All seven resistant subpopulations contained about 20,000 high-affinity, dexamethasone binding sites/cell. Between 57 and 80% of these presumptive receptor sites underwent nuclear translocation under standard assay conditions. No resistant variants exhibited significantly reduced dexamethasone binding or nuclear translocation properties.
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