The effects of 6-diazo-5-oxo-l-norleucine (DON) on the conversions of orotic acid-6-C14 to RNA pyrimidines and of glycine-2-C14 to RNA purines were studied in suspensions of Novikoff tumor cells in vitro.
The concentrations of DON required to inhibit the amination step in the biosynthesis of cytidine nucleotides were about 10 times the concentrations required to inhibit completely the biosynthesis de novo of purine nucleotides. The degree of inhibition in both cases was diminished by the presence of glutamine in the medium.
The inhibition by DON of the amination step in cytidine nucleotide formation was shown to be irreversible. The effect of glutamine was to delay or partially prevent the inhibition.
The formation of cytidine nucleotides was observed to be stimulated by the minimal concentration of DON effective in the inhibition of purine nucleotide formation; an explanation of this anomaly is offered.
This investigation was supported by a grant from the American Cancer Society (P-146A).