Mutants of CHO cells resistant to the protein synthesis inhibitor emetine: Genetic and biochemical characterization of second-step mutants

Second-step mutants highly resistant to the protein synthesis inhibitor emetine (EmtRII) have been selected from emetine resistant (EmtRI) Chinese hamster ovary cells described earlier. The frequency of the EmtRII mutants was increased 50- to 75-fold after mutagenesis, and none of these highly resistant mutants could be selected in one step using wild-type cells. Like the EmtRI mutants, the increased resistance of EmtRII mutants results from another lesion in the polyribosomal fraction, as measured by the effects of emetine in fractionated extracts. As with the first-step mutants, the EmtRII isolates behave recessively in somatic cell hybrids. Segregation studies have shown that the EmtR lesions are not on the X chromosome, and in at least one isolate there is evidence that the EmtRI and EmtRII mutations may occur at different sites.