Controlled delivery of nitric oxide for cytotoxicity studies

Endogenous synthesis of nitric oxide (NO) is essential for many physiological functions, including the immune defense. However, the sustained, high production of NO by immune cells (macrophages) that accompanies chronic inflammation may be cytotoxic, mutagenic and carcinogenic. To better understand the roles of NO and its various reactive derivatives (e.g., N203 and ONOO-) in cancer, it is important to know the NO concentration and the total NO dose that tissue cells are exposed to during inflammation. To obtain this quantitative information, methods are needed for exposing cells to physiological levels of NO and its derivatives over relatively long periods of time. This research has therefore focused on developing in vitro delivery systems that mimic the in vivo release of NO. To permit continuous NO exposures over lengthy periods, an apparatus was fabricated which utilizes gas-permeable polydimethylsiloxane tubing to supply both NO and 02 to a stirred, cylindrical vessel. Mass transfer in this system was characterized by measuring the delivery rates of NO or 02 alone, and of NO to air-saturated solutions. It was found that the total flux of nitrogen species into the liquid was 40-90% greater in the presence of 02, depending on the NO partial pressure in the gas. Also, the simultaneously measured mass transfer coefficients for NO and 02 differed greatly from the corresponding unreactive values. An analysis of the data using diffusion-reaction models showed that NO oxidation in the aqueous boundary layer contributed very little to the nitrogen flux increase or to variations in the mass transfer coefficients. However, the unusually strong dependence of the delivery rates on chemical reactions could be explained by postulating that partial oxidation of NO to NO2 occurred within the membrane, with a rate constant of ...

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2003

Author dc:creator

• Wang, Chen, 1972-

Advisor dc:contributor.advisor

• William M. Deen.

• Chemical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/29604

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/29604