Rebecca R. Laposa #, Jeffrey T. Henderson $, and Peter G. Wells #, @, !

# Faculty of Pharmacy Rm 514, University of Toronto, Toronto, Ontario, Canada
19 Russell St., Toronto, ONT M5S 2S2

$ Faculty of Pharmacy Rm 212, University of Toronto, Toronto, Ontario, Canada
19 Russell St., Toronto, ONT M5S 2S2

@ Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada

! Corresponding author: Telephone: 416-978-3221, Fax: 416-267-7797, Email: pg.wells@utoronto.ca

FASEB Journal, 17(10), 1343-1345, 2003.

Abstract

8-Oxo-deoxyguanosine (8-oxo-dG) is a pervasive oxidative DNA lesion formed by endogenous oxidative stress and enhanced by drugs and environmental chemicals. This lesion results in transcriptional errors and mutations, and is linked to neurodegeneration, teratogenesis, cancer and other pathologies. We demonstrate that the neonatal central nervous system of transgenic mice carrying the tetracycline-regulable DNA repair gene formamidopyrimidine DNA glycosylase (fpg) has a 50% reduction in 8-oxo-dG levels. This enhanced DNA repair is suppressed by treatment with doxycycline. For the first time, this murine model permits the level of a specific DNA oxidation product to be regulated in a temporally- and spatially-specific manner, allowing its role as a primary or secondary factor in neurodegenerative disease to be determined in vivo.

Full Paper
 

 
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