Oxidative stress, inflammation, and DNA damage in rats after intratracheal instillation or oral exposure to ambient air and wood smoke particulate matter

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Pernille Høgh Danielsen, Steffen Loft, Nicklas Raun Jacobsen, Keld Alstrup Jensen, Herman Autrup, Jean-Luc Ravanat, Håkan Wallin, Peter Møller

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 (edG) 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 edG 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.
Original languageEnglish
JournalToxicological Sciences
Volume118
Issue number2
Pages (from-to)574-85
Number of pages12
ISSN1096-6080
DOIs
Publication statusPublished - 1 Dec 2010

    Research areas

  • Administration, Oral, Animals, Biological Markers, Bronchoalveolar Lavage Fluid, Cell Count, Chemokine CCL2, Chemokine CXCL2, Cytokines, DNA Adducts, DNA Damage, DNA Glycosylases, Gene Expression, Heme Oxygenase-1, Intubation, Intratracheal, Male, Membrane Proteins, Oxidative Stress, Particulate Matter, Pneumonia, Rats, Rats, Inbred F344, Smoke, Wood

ID: 33595655