Diffusion and reaction of nitric oxide in cell cultures

Nitric oxide (NO) is synthesized throughout the body and its intercellular signalling and other functions are necessary for health. However, its mutagenic effects make it a potential cause of cancer, if it is produced at a high enough rate for a sufficient time. Sustained overproduction of NO may occur, for example, in macrophages as part of the immune response to certain chronic infections. The mutagenic effects of NO are thought to be due largely to trace compounds such as nitrous anhydride (N2O3) and peroxynitrite (ONOO-), formed during its reaction with molecular oxygen or superoxide anion (O2-)- It is not technically feasible to monitor the concentrations of these species under most conditions of interest, yet assessing the amounts of these species reaching target cells is essential to correlate levels of toxicity and to extrapolate to pathological situations in the body. Accordingly, mathematical models are needed to predict the concentrations of NO and related compounds in cell cultures. A reaction-diffusion model was developed to predict the fate of NO released by activated macrophages attached to microcarrier beads suspended in a stirred vessel, where experimental data were obtained previously. In the analysis the reactor was divided into a "stagnant film" with position-dependent concentrations and a well-mixed bulk solution. Model predictions based on independently determined kinetics and mass transfer parameters were found to be in good agreement with the experimental results for the concentration of NO in bulk solution, nitrite and nitrate accumulation rate, as well as the NO loss to the head space. The coupling between reaction and diffusion was found to greatly influence the spatial distributions of NO, O2-, as well as N2O3 and peroxynitrite, the potential mediators of cytotoxicity and mutagenicity.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2001

Author dc:creator

• Chen, Bo, 1970-

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/1721.1/8205

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/8205