Isolation and characterization of L-cell variants with altered sensitivity to glucocorticoids.

Stable glucocorticoid-resistant receptor-containing (R+) variants of L cells have been obtained and characterized. Five clones of such cells were obtained after chemical mutagenesis of the A9HT cell line. These clones and an additional, spontaneously resistant subclone of the LB82 cell line all contain glucocorticoid receptors which appear normal with regard to quantity, affinity for steroids, and in vivo localization in subcellular compartments. Somatic cell hybrids were formed between two of these R+-resistant clones, a previously isolated R-resistant clone, and three different sensitive L cell parents. In no case was steroid resistance dominant. Thus, these resistant L cells appear to be candidates for complementation analysis. The R+-resistant clones may be hindered in as yet undefined steps of glucocorticoid action.