Isolation and characterization of dexamethasone-resistant mutants from human lymphoid cell line CEM-C7.

摘要: Fifty-four independent dexamethasone-resistant clones were isolated from the clonal, glucocorticoid-sensitive human leukemic T-cell line CEM-C7. Resistance to 1 microM dexamethasone was acquired spontaneously at a rate of 2.6 X 10(-5) per cell generation as determined by fluctuation analysis. After mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), phenotypic expression time for resistance be 3 days. Spontaneous acquisition 0.1 mM 6-thioguanine appeared occur much slower rate, 1.6 10(-6) generation. However, after MNNG this resistant phenotype greater than 11 days, suggesting that different rates two phenotypes measured analysis results disparate times. The mutagens ICR 191 and effective in increasing fraction cells mutagenized cultures; produced 35.6-fold increase, an 8.5-fold increase. All spontaneous contained glucocorticoid receptors, usually less half amount found parental clone. They are therefore strikingly derived mouse lines S49 W7. Dexamethasone-resistant CEM-C7 contained, on average, lower concentrations receptor did those spontaneously, one clone no detectable receptor. These consistent mutational origin these haploid or functionally hemizygous locus. also suggest is useful system mutation assay.