The relationship between induced mutation frequency and chromosome dosage in established mouse fibroblast lines.
The frequencies of induced mutation to ouabain (OUA) and 6-thioguanine (6TG) resistance were compared in two established mouse fibroblast lines with different doses of the active X chromosome. The activity states of the X chromosomes were determined by DNA replication studies. Mutation frequency to 6TG R, an X-linked recessive phenotype, was inversely related to dosage whereas OUA R, a codominant phenotpye, occurred with equal frequency in both lines. 6TG R clones isolated from the line containing a majority of cells with two active X chromosomes were monosomic for the active X chromosome. Enzyme activity studies of these cytologically monosomic lines yieled results that were consistent with the presence of a single active X chromosome. The findings strongly support the hypothesis that mutation frequency is dependent on gene dosage.
D000483:Alleles; D002460:Cell Line; D004261:DNA Replication; D004351:Drug Resistance; D005260:Female; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007621:Karyotyping; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D009154:Mutation / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology; D012730:Sex Chromosomes / Q000187:drug effects*; D013866:Thioguanine / Q000494:pharmacology; D014960:X Chromosome / Q000187:drug effects*
D008769:Methylnitronitrosoguanidine; D010042:Ouabain; D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine