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Respiratory tract inflammation, production of mediators of inflammation capable of reaching the brain, systemic circulation of PM, and disruption of the nasal respiratory and olfactory barriers are likely in these populations. DNA damage is crucial in aging and in age-associated diseases such as Alzheimer's disease. We evaluated apurinic\/apyrimidinic (AP) sites in nasal and brain genomic DNA, and explored by immunohistochemistry the expression of nuclear factor NF \u03baB p65, inducible nitric oxide synthase (iNOS), cyclo-oxygenase 2 (COX2), metallothionein I and II, apolipoprotein E, amyloid precursor protein (APP), and beta-amyloid1-42 in healthy dogs naturally exposed to urban pollution in Mexico City. Nickel (Ni) and vanadium (V) were measured by inductively coupled plasma mass spectrometry (ICP-MS). Forty mongrel dogs, ages 7 days\u201410 years were studied (14 controls from Tlaxcala and 26 exposed to urban pollution in South West Metropolitan Mexico City (SWMMC)). Nasal respiratory and olfactory epithelium were found to be early pollutant targets. Olfactory bulb and hippocampal AP sites were significantly higher in exposed than in control age matched animals. Ni and V were present in a gradient from olfactory mucosa &gt; olfactory bulb &gt; frontal cortex. Exposed dogs had (a) nuclear neuronal NF \u03baB p65, (b) endothelial, glial and neuronal iNOS, (c) endothelial and glial COX2, (d) ApoE in neuronal, glial and vascular cells, and (e) APP and \u03b2 amyloid1-42 in neurons, diffuse plaques (the earliest at age 11 months), and in subarachnoid blood vessels. Increased AP sites and the inflammatory and stress protein brain responses were early and significant in dogs exposed to urban pollution. Oil combustion PM-associated metals Ni and V were detected in the brain. There was an acceleration of Alzheimer's-type pathology in dogs chronically exposed to air pollutants. Respiratory tract inflammation and deteriorating olfactory and respiratory barriers may play a role in the observed neuropathology. These data suggest that Alzheimer's disease may be the sequela of air pollutant exposures and the resulting systemic inflammation.<\/jats:p>","DOI":"10.1080\/01926230390226645","type":"journal-article","created":{"date-parts":[[2007,7,8]],"date-time":"2007-07-08T19:06:21Z","timestamp":1183921581000},"page":"524-538","source":"Crossref","is-referenced-by-count":305,"title":["DNA Damage in Nasal and Brain Tissues of Canines Exposed to Air Pollutants Is Associated with Evidence of Chronic Brain Inflammation and Neurodegeneration"],"prefix":"10.1177","volume":"31","author":[{"given":"Lilian","family":"Calderon-Garciduenas","sequence":"first","affiliation":[{"name":"Environmental Pathology Program, University of North Carolina at Chapel Hill, North Carolina 27599-7310, USA, , Instituto Nacional de Pediatr\u00eda, Mexico City 14410, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert R.","family":"Maronpot","sequence":"additional","affiliation":[{"name":"National 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