THE INFLUENCE OF DELIVERY RATE ON THE CHEMISTRY AND BIOLOGICAL EFFECTS OF NITRIC-OXIDE

Nitric oxide can be introduced slowly and steadily into aqueous soluti ons, including cell culture media, over extended periods of time via s emipermeable Silastic (a registered trademark of the Dow Coming Corp.) polymer membranes. The rates of introduction are predictable and repr oducible and can approach rates of nitric oxide production by stimulat ed cells, such as macrophages, that express inducible nitric oxide syn thases. DNA damage in Chinese hamster ovary cells by membrane-delivere d nitric oxide is comparable to that observed in the DNA of stimulated macrophages. Toxicity and mutagenicity of nitric oxide toward Salmone alla typhimurium, toxicity of nitric oxide toward Chinese hamster ovar y cells, and nitrosation of dimethylmorpholine are all more efficient when nitric oxide is delivered by membrane than when an equivalent amo unt of gaseous nitric oxide is added by syringe.