Oxidative DNA damage by cytotoxic N-oxides of 1-hydroxyphenazine: Toward a molecular understanding of the bacterial virulence factor 1-hydroxyphenazine

TOXI 98

Sarmistha Sinha, ssg84@mizzou.edu and Kent Gates, GatesK@missouri.edu. Department of Chemistry, University of Missouri-Columbia, 601 South College Avenue, columbia, MO 65211
1-Hydroxyphenazine(1) is a secondry metabolite of P.aeruginosa which colonizes the airways of the patients of cystic fibrosis. It is thought that 1-hydroxyphenazine is a bacterial virulence factor that plays an important role in tissue damage, but the mechanisms of action are not well studied. Here we report chemical properties of 1-hydroxyphenazine which might help to explain its biological activities. Our results suggest that 1-hydroxyphenazine and its potential N-oxide metabolites, in tandem with bioreductive enzyme systems such as NADPH:cytochrome P450 reductase can generate oxidative stress via redox cycling mechanisms and via the release of hydroxyl radical.

 

Poster Session and Awards
6:00 PM-10:00 PM, Tuesday, August 21, 2007 BCEC -- 204 A/B, Poster

Division of Chemical Toxicology

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007