N omega-hydroxy-L-arginine, a reactional intermediate in nitric oxide biosynthesis, induces cytostasis in human and murine tumor cells.
Conversion of L-arginine to L-citrulline and nitric oxide (NO) by NO synthase induced in the murine EMT-6 cells resulted in the release of a large amount of the stable reactional intermediate N omega-hydroxy-L-arginine into the extracellular medium. We have prepared [3H]N omega-hydroxy-L-arginine biosynthetically, and shown that, after its uptake, this molecule can induce cytostasis in NO synthase-deficient P-815 and U-937 tumor cells. This long-lived intermediate could behave as a supplier of NO or other toxic molecules in cell-cell interactions.
Chénais
B
B
CNRS URA 1116, Université Paris-XI, Orsay, France.
Yapo
A
A
Lepoivre
M
M
Tenu
J P
JP
D000230:Adenocarcinoma; D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D001692:Biological Transport / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D008325:Mammary Neoplasms, Experimental; D012515:Mast-Cell Sarcoma; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D014407:Tumor Cells, Cultured
D009569:Nitric Oxide; C068309:N(omega)-hydroxyarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases