Genomic consequences of DNA oxidation by peroxynitrite

The radicals nitric oxide and superoxide are produced endogenously by activated macrophages and neutrophils and combine in a diffusion-limited reaction to form peroxynitrite, a powerful oxidizing and nitrating agent capable of damaging a variety of biomolecules, including DNA. Of the four nucleobases of DNA, guanine has the lowest oxidation potential and thus considerable attention has been given to the study of the oxidation of this base by peroxynitrite. A variety of DNA lesions are generated from guanine including guanidinohydantoin, spiroiminodihydantoin, oxaluric acid, urea, 2-aminoimidazolone, and 5-guanidino-4-nitroimidazole. In order to assess the biological significance and consequences of peroxynitrite-damaged DNA, it is essential that these lesions be characterized for their genotoxic and mutagenic potential. This work focuses on the elucidation of those properties. In the first study, the 2'-deoxynucleoside of 5-guanidino-4-nitroimidazole was chemically synthesized and incorporated into an oligonucleotide by the phosphoramidite method. In the second study, the genotoxic and mutational properties of 2-aminoimidazolone and 5-guanidino-4-nitroimidazole were determined in wild-type uninduced and SOS-induced E. coli.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2006

Author dc:creator

• Neeley, William Louis

Advisor dc:contributor.advisor

• John M. Essigmann.

• Chemistry.

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/1721.1/37359
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/37359

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/37359