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

Nitric oxide can be introduced slowly and steadily into aqueous solutions, including cell culture media, over extended periods of time via semipermeable Silastic (a registered trademark of the Dow Coming Corp.) polymer membranes. The rates of introduction are predictable and reproducible and can approach rates of nitric oxide production by stimulated cells, such as macrophages, that express inducible nitric oxide synthases. DNA damage in Chinese hamster ovary cells by membrane-delivered nitric oxide is comparable to that observed in the DNA of stimulated macrophages. Toxicity and mutagenicity of nitric oxide toward Salmonealla typhimurium, toxicity of nitric oxide toward Chinese hamster ovary cells, and nitrosation of dimethylmorpholine are all more efficient when nitric oxide is delivered by membrane than when an equivalent amount of gaseous nitric oxide is added by syringe.