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Exposure to lead (Pb) and the developmental origin of oxidative DNA damage in the aging brain
Author(s) -
Bolin Celeste M.,
Basha Riyaz,
Cox David,
Zawia Nasser H.,
Maloney Bryan,
Lahiri Debomoy K.,
CardozoPelaez Fernando
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-5091fje
Subject(s) - sod1 , dna damage , oxidative stress , sod2 , superoxide dismutase , neurodegeneration , reactive oxygen species , chemistry , deoxyguanosine , dna glycosylase , 8 hydroxy 2' deoxyguanosine , dna repair , medicine , endocrinology , oxidative damage , biochemistry , dna oxidation , biology , dna , disease
Oxidative damage to DNA has been associated with neurodegenerative diseases. Developmental exposure to lead (Pb) has been shown to elevate the Alzheimer's disease (AD) related β‐amyloid peptide (Aβ), which is known to generate reactive oxygen species in the aging brain. This study measures the lifetime cerebral 8‐hydroxy‐2'‐deoxyguanosine (oxo 8 dG) levels and the activity of the DNA repair enzyme 8‐oxoguanine DNA glycosylase (Ogg1) in rats developmentally exposed to Pb. Oxo 8 dG was transiently modulated early in life (Postnatal day 5), but was later elevated 20 months after exposure to Pb had ceased, while Ogg1 activity was not altered. Furthermore, an age‐dependent loss in the inverse correlation between Ogg1 activity and oxo 8 dG accumulation was observed. The effect of Pb on oxo 8 dG levels did not occur if animals were exposed to Pb in old age. These increases in DNA damage occurred in the absence of any Pb‐induced changes in copper/zinc‐superoxide dismutase (SOD1), manganese‐SOD (SOD2), and reduced‐form glutathion (GSH). These data suggest that oxidative damage and neurodegeneration in the aging brain could be impacted by the developmental disturbances.