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05.30.2007: Vasileios Dendroulakis (ChemE/BioE)
Damaged building blocks of DNA: can they be used as indicators of
inflammation?
Abstract:
Chronic inflammation is intimately associated with human diseases such
as cancer and this relation is thought to be based on the secretion of
reactive oxygen and nitrogen species from specialized white blood cells
at sites of inflammation: apart from eliminating infectious agents these
reactive chemical mediators are also thought to cause damage to
surrounding host cells. Among those mediators, nitric oxide radical
(NO^? ) is produced at relatively high levels by activated macrophages
and reacts with oxygen (O_2 ) to form nitrous anhydride (N_2 O_3 ), the
major nitrosating agent responsible for deamination of DNA bases, giving
rise to non-canonical nucleobases. Although products of deamination can
be readily quantified in solutions of purified DNA exposed to NO^? and
O_2 , work in our laboratory has shown little nucleobase deamination in
genomic DNA from inflamed tissues in mice. These modest results have
motivated us to shift the focus of our studies to the more solvent
exposed nucleotides, the building blocks of DNA and RNA, as potential
indicators of inflammation-related cell damage. In this talk I will
describe our first steps towards the quantification of deaminated
nucleotides in cells exposed to NO^? and O_2 .
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