When plated in medium containing 0.5 microgram/ml
coformycin and
adenosine (or
adenine) fibroblasts were killed, even if
pyrimidines were supplied. Measurements of
N-formylglycine amide ribonucleotide synthesis showed that lethality is a manifestation of
purine starvation. In the case of
adenosine kinase deficient cells, growth was restored by
hypoxanthine. The adenylic derivatives block only
purine biosynthesis, presumably by inhibition of PRPP-amidotransferase. In this same medium, wild-type cells exhibited symptoms of PRPP deprivation:
purine and
pyrimidine syntheses were both shut off and
HGPRT was simultaneously inactivated. The pleiotropic control by
adenosine was abolished in
adenosine-resistant mutants that behaved as PRPP "over-producers." These mutations conferred partial resistance to various toxic
purine and
pyrimidine analogs and preserved
HGPRT activity in
adenosine-containing medium. This permits selection against these mutants. Evidence suggesting that
adenosine kinase products may fulfill a specific function in the regulation of PRPP synthesis is discussed.