EFFECTS OF CYTOSINE ARABINOSIDE ON DIFFERENTIAL GENE EXPRESSION IN EMBRYONIC NEURAL RETINA I . Accumulation of Glutamine Synthetase with Suppression of Macromolecular Synthesis

The analogue of cytidine, cytosine arabinoside (Ara-C), elicited a significant increase in the level of glutamine synthetase (GS) in embryonic chick neural retina in the absence of the steroid inducer of the enzyme . The increase was due to de novo synthesis of GS and was mediated by RNA which accumulated in the presence of the effective concentration of Ara-C . Accumulation of GS did not result from the inhibition of DNA synthesis for which Ara-C is best known . This new effect of Ara-C involves differential suppression of macromolecular synthesis in this system : the concentration of Ara-C which caused maximum GS accumulation suppressed overall protein and RNA syntheses 65-75% without inhibiting the transcription and translation of templates essential for GS synthesis . Withdrawal of Ara-C resulted in restoration of RNA synthesis and cessation of GS accumulation, even though preformed templates for the enzyme were present ; however, if all RNA synthesis was arrested with actinomycin D at the time of Ara-C withdrawal, GS continued to accumulate . The results are consistent with the hypothesis that Ara-C differentially affects the activity of structural and regulatory genes involved in the regulation of GS levels in the retina : Ara-C allows transcription of the enzymespecific templates, but reversibly inhibits the expression of regulatory genes which limit the accumulation of GS .