Quenching of the tyrosyl free radical of ribonucleotide reductase by nitric oxide. Relationship to cytostasis induced in tumor cells by cytotoxic macrophages.

M Lepoivre, JM Flaman, P Bobé, G Lemaire… - Journal of Biological …, 1994 - ASBMB
Nitric oxide (NO) synthesized by macrophages inhibits tumor cell replication. NO also
inhibits ribonucleotide reductase, an enzyme essential for DNA synthesis, probably by
quenching the catalytically active tyrosyl free radical of its R2 subunit. The role of this
inhibition in NO-mediated cytostasis was thus evaluated. After a 4-h coculture with
macrophages, quenching of the radical was demonstrated by electron paramagnetic
resonance spectroscopy in transfected L1210-R2 cells over-expressing the R2 protein …