Elevated Glucocorticoid Receptor Binding in Cultured Human Lymphoblasts following Hydroxyurea Treatment: Lack of Effect on Steroid Responsiveness1

Abstract

While studying the effects of chemotherapy on glucocorticoid receptor (GR) binding levels in hentatological malignancies, we observed a sizable increase in nuclear GR binding of (3H)dexamethasone in peripheral leukocytes from a chronic basophilic leukemia patient following treat ment with hydroxyurea plus prednisone, but not after prednisone alone. This apparent clinical effect of hydroxyurea led to an examination of hydroxyurea effects on GR binding and sensitivity in the glucocorticoidsensitive human lymphoblast cell line GM4672A. GR binding levels in GM4672A cells were measured following a 3-day exposure to 50 ¿IM hydroxyurea, a concentration chosen to have a minimal but measurable effect on cellular growth rates with little or no effect on cellular viability. Under these conditions, nuclear (3H]dexamethasone receptor binding measured by Scatchard analysis using a whole-cell assay was elevate

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