Effects of fluorodeoxyuridine on growth and choline acetyltransferase activity in fetal rat brain cells in surface culture

Inhibition of DNA synthesis by 5‐fluoro‐2‐deoxyuridine in cultures of rapidly growing fetal rat brain cells resulted in a marked decrease in the development of total activity and a stimulation of specific activity (pmolesmin\μg DNA) of the enzyme choline acetyltransferase, a putative neuronal marker. Similar treatment of higher density, less rapidly dividing cultures of the same age resulted in no change in total activity development, although an increment in specific activity was again found. The findings appeared to be the result of inhibition of DNA synthesis by fluorodeoxyuridine, rather than secondary effects of the drug, and indicate either that the nucleotide analog specifically inhibited choline acetyltransferase gene expression in rapidly growing, but not in stationary cultures, or that cells capable of producing the enzyme activity were able to proliferate in culture. If the latter were true and if cells producing the enzyme were, in fact, neurons, it may be possible to clone untransformed neurons for in‐depth study in a culture system.