Nucleobase deamination as a biomarker of inflammatory processes

(cont.) kinetic studies. Moderate increases ([approximately]30%) in nucleobase deamination products were observed in the SJL mice bearing the RcsX tumor, but the biological meaning of these increases awaits studies of DNA repair kinetics. dO was not detected in any study at levels above 5 per 10⁸ nt, leading to the prediction that it will not be present at significant levels in inflamed tissues in humans. As a complement to the LC-MS method for the quantification of nucleobase deamination products, enzymatic probes were also developed for oxidative and nitrosative DNA lesions. These probes would not only allow differential quantification of the two types of DNA damage, but would also allow the lesions to be mapped in any DNA sequence by coupling their activity with the technique of ligation-mediated PCR. As an extension of the biomarker study, the effects of ONOO⁻ dose and dose-rate on the DNA damage and mutations induced in the supF gene were investigated. The observations suggest that both the dose and dose-rate at which a genetic target is exposed to ONOO⁻ substantially influence the damage and mutational response and these parameters will need to be considered in assessing the potential effects of ONOO⁻ in vivo. Finally, an extended study using the analytical method developed in this thesis yielded results in E. coli consistent with a new paradigm: perturbations of nucleobase metabolism may lead to incorporation of the purine precursors hypoxanthine (I) and xanthine (X) into DNA. This can be regarded as another endogenous process causing DNA damage that may lead to human diseases such as cancer ...

Department dc:contributor.department

Massachusetts Institute of Technology. Biological Engineering Division.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2005

Author dc:creator

• Dong, Min, 1968-

Advisor dc:contributor.advisor

• Peter C. Dedon.

• Biological Engineering Division.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

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

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/28763

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/28763