Glucorticoid resistance in murine lymphoma and thymoma lines

Abstract

The thymoma line W7 contains 30,000 dexamethasone-binding sites per cell and gives rise to glucocorticoid-resistant variants at a frequency less than 1.6 X 10(-9); the lymphoma S49 contains one-half that amount of receptor, is resistant to low concentrations of dexamethasone, and gives rise to fully resistant variants at high frequency. These results suggest that S49 is functionally haploid (r+/-) for a gene coding for the receptor while W7 appears diploid for that locus (r+/+). Derivatives of the W7 (r+/+) line, selected for resistance to low concentrations of dexamethasone, have the same properties as S49. These putative W7's (r+/-) give rise to the same types of receptor variants as S49 and in the same proportion; 80 to 90% are "receptorless" (r-) while 10 to 20% are "nuclear transfer defective" (nt-). A total of 127 variants resistant to high concentrations of dexamethasone were derived from the W7 (r+/+) line after mutagenesis. All are receptor variants but N-methyl-N'-nitro-N-nitrosoguanidine and ethyl methanesulfonate induce only 60 to 70% r- variants, confirming the presence of two r+ alleles in the parental line. Ultraviolet light induces a higher proportion (87%) of r+ variants, as expected from the introduction of breaks and deletions in DNA.