EPA Science Inventory

Myeloperoxidase-produced Genomic DNA-centered Radicals and Protection by Resveratrol

Citation:

Gomez-Mejibal, S. E., R. A. Faris, Z. Zhai, S. Mannava, J. Chilakapati, M. T. Asby, R. P. Mason, K. T. KITCHIN, AND D. C. Ramirez. Myeloperoxidase-produced Genomic DNA-centered Radicals and Protection by Resveratrol. THE JOURNAL OF BIOLOGICAL CHEMISTRY 285(26):20062-71, (2010).

Description:

Myeloperoxidase (MPO) released by activated neutrophils, production of hypochlorous acid (HOCI) and oxidation of the genomic DNA in epithelial cells is thought to initiate and promote carcinogenesis. In this study we applied the 5,5-dimethyl-l-pyrroline N-oxide (DMPO)-based i;nmuno-spin trapping technique to investigate M PO-driven, HOCI-triggered, DNA-centered radicals in biochemical and cell models and to test whether resveratro! scavenges HOCI formed inside cells and consequently block DNA-centered radical formation. We found that HOC! produced by MPO in close proximity to the genome produces DNA-centered radicals. Resveratrol, a cell-permeable scavenger of HOCI, blocked DNA-centered radical formation. DMPO might be useful to stop early DNA oxidation and to detect early the oxidative DNA damage in site ofinflammation. Study ofDNa-centered radicals in sites of inflammation will help to understand the biochemical bases of' fiGel-induced genomic instability and find new therapeutic strategies to block early inflammation-induced carcinogenesis.

Purpose/Objective:

Inflammation and locally produced free radicals are now suspected as being major causes of some types of cancers. This study looked at myeloperoxidase activity as a way in which free radicals can be produced. Both oxidation of DNA, attack on DNA by free radicals and the production of free radicals where the unpaired electron is centered on the DNA backbone all can contribute to carcinogenesis. This report directly measures the last of these three possibilities (the production of free radicals where the unpaired electron is centered on the DNA backbone).

URLs/Downloads:

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Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Projected Completion Date: 11/05/2013
Record Last Revised: 10/29/2012
Record Created: 12/01/2009
Record Released: 12/01/2009
OMB Category: Other
Record ID: 217121

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB

INTEGRATED SYSTEMS TOXICOLOGY DIVISION

GENETIC AND CELLULAR TOXICOLOGY BRANCH