Isolation and characterization of dexamethasone-resistant mutants from human lymphoid cell line CEM-C7
Fifty-four independent dexamethasone-resistant clones were isolated from the clonal, glucocorticoid-sensitive human leukemic T-cell line CEM-C7. Resistance to 1 ..mu..M dexamethasone was acquired spontaneously at a rate of 2.6 x 10/sup -5/ per cell per generation as determined by fluctuation analysis. After mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the phenotypic expression time for dexamethasone resistance was determined to be 3 days. The mutagens ICR 191 and MNNG were effective in increasing the dexamethasone-resistant fraction of cells in mutagenized cultures; ICR 191 produced a 35.6-fold increase, and MNNG produced an 8.5-fold increase. All the spontaneous dexamethasone-resistant clones contained glucocorticoid receptors, usually less than half of the amount found in the parental clone. They are therefore strikingly different from dexamethasone-resistant clones derived from the mouse cell lines S49 and W7. Dexamethasone-resistant clones isolated after mutagenesis of CEM-C7 contained, on the average, lower concentrations of receptor than did those isolated spontaneously, and one clone contained no detectable receptor. These results are consistent with a mutational origin for dexamethasone resistance in these human cells at a haploid or functionally hemizygous locus. They also suggest that this is a useful system for mutation assay.
- Research Organization:
- Lab. of Biochemistry, Div. of Cancer Biology and Diagnosis, National Cancer Institute, Bethesda, MD 20205
- OSTI ID:
- 6030012
- Journal Information:
- Mol. Cell. Biol.; (United States), Vol. 1:6
- Country of Publication:
- United States
- Language:
- English
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DEXAMETHASONE
RECEPTORS
NITROSO COMPOUNDS
MUTAGENESIS
TOXICITY
ENZYME INDUCTION
CELL CULTURES
GENE REGULATION
GUANIDINES
HAPLOIDY
LEUKEMIA
LYMPHOCYTES
MAN
MOLECULAR BIOLOGY
MUTAGENS
MUTANTS
PHENOTYPE
SENSITIVITY
TECHNOLOGY ASSESSMENT
ADRENAL HORMONES
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
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CONNECTIVE TISSUE CELLS
CORTICOSTEROIDS
DISEASES
GLUCOCORTICOIDS
HEMIC DISEASES
HYDROXY COMPOUNDS
KETONES
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MEMBRANE PROTEINS
NEOPLASMS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PLOIDY
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SOMATIC CELLS
STEROIDS
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550400* - Genetics
550200 - Biochemistry