Complementation between glucocorticoid receptor and lymphocytolysis in somatic cell hybrids of two...

Somatic hybrids between two glucocorticoid-resistant clonal cell lines, CEM C1 and ICR-27, isolated independently from the CCRF-CEM human lymphoblastoid cell line, were constructed to investigate the complementation effect between the glucocorticoid receptor and the gene product(s) for inducing receptor-mediated lymphocytolysis. CEM C1 (r+ly-) has a normal amount of functional glucocorticoid receptor as compared to the steroid-sensitive clonal line CEM C7. Clone ICR-27 (r-ly?), which was originally isolated following mutagenesis of CEM C7 with the mutagen ICR 191, has few glucocorticoid receptors as determined by whole-cell receptor assay. The eight randomly selected CEM C1 X ICR-27 hybrid clones all showed sensitivity to 10(-6) M dexamethasone (ly+). The receptor site content of two near-tetraploid hybrids chosen for analysis was close to that of CEM C1 (r+). Hybrids constructed between CEM C1 and the receptor-bearing, steroid-sensitive clone, CEM C7 (r+ly+) also showed glucocorticoid sensitivity, and their receptor sites corresponded to the sum of those of CEM C1 and CEM C7 (r+r+ly+). These results indicate: that CEM C1 has no trans-active inhibitor of lysis; that CEM C1 has intact glucocorticoid receptor; and that ICR-27 and CEM C1 complement one another to restore lymphocytolysis. Therefore, CEM C1 cells can serve as a donor of human glucocorticoid receptors.