Variants inducible for glutamine synthetase in V79-56 cells

V79-56 cells have an absolute requirement for exogenous glutamine and are not inducible for glutamine synthetase. Prototrophs arise spontaneously at approximately 1.0 X 10(-5) per cell per generation as measured by fluctuation tests. Higher frequencies of glutamine-independent variants may be obtained by treatment with the mutagen ethyl methane sulfonate, as well as by exposure to 5-azacytidine and sodium butyrate, which act primarily by affecting gene expression. Variants of all types show marked elevation of glutamine synthetase activity. Although this activity declines toward constitutive levels in the presence of glutamine, it is still inducible in variant cells. These populations, after a lag, regain the ability for progressive growth in glutamine-free medium. Thus, the stable variation seen here is in the potential for induction, rather than steady-state expression of glutamine synthetase at a higher level.