title: Oxidative stress, inflammation, and DNA damage in rats after intratracheal instillation or oral exposure to ambient air and wood smoke particulate matter.
abstract: Wood combustion is a significant source of ambient particulate matter (PM) in many regions of the world. Exposure occurs through inhalation or ingestion after deposition of wood smoke particulate matter (WSPM) on crops and food. We investigated effects of ambient PM and WSPM by intragastric or intratracheal exposure in terms of oxidative stress, inflammation, genotoxicity, and DNA repair after 24 h in liver and lung tissue of rats. Rats were exposed to WSPM from high or low oxygen combustion and ambient PM collected in areas with and without many operating wood stoves or carbon black (CB) at the dose of 0.64 mg/kg body weight. The levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine, 1,N(6)-etheno-2'-deoxyadenosine, and 1-N(2)-etheno-2'-deoxyguanosine (εdG) were significantly increased with 23% (95% confidence interval [CI]: 0.1-45%), 54% (95% CI:18-90%), and 73% (95% CI: 31-134%) in the liver of rats exposed orally to CB, respectively. Rats orally exposed to PM from the wood stove area and low oxygen combustion WSPM (LOWS) had 35% (95% CI: 0.1-71%) and 45% (95% CI: 10-82%) increased levels of εdG in the liver, respectively. No significant differences were observed for bulky DNA adducts. Increased gene expression of proinflammatory cytokines, heme oxygenase-1, and oxoguanine DNA glycosylase 1 was observed in the liver following intragastric exposure and in the lung following instillation in particular of LOWS. Exposure to LOWS also increased the proportion of neutrophils in BAL fluid. These results indicate that WSPM and CB exert the strongest effect in terms of oxidative stress-induced response, inflammation, and genotoxicity in the organ closest to the port of entry.
authors.affiliation: Section of Environmental Health, Department of Public Health, University of Copenhagen, DK-1014 Copenhagen, Denmark.
authors.forename: Pernille Høgh
authors.initials: PH
authors.lastname: Danielsen
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
authors.forename: Nicklas Raun
authors.initials: NR
authors.lastname: Jacobsen
authors.forename: Keld Alstrup
authors.initials: KA
authors.lastname: Jensen
authors.forename: Herman
authors.initials: H
authors.lastname: Autrup
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Ravanat
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallin
authors.forename: Peter
authors.initials: P
authors.lastname: Møller
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D018736:DNA Adducts / Q000032:analysis; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D007442:Intubation, Intratracheal; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D052638:Particulate Matter / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012906:Smoke / Q000009:adverse effects*; D014934:Wood
chemical_list: D015415:Biomarkers; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D016207:Cytokines; D018736:DNA Adducts; D008565:Membrane Proteins; D052638:Particulate Matter; D012906:Smoke; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse