DNA damage in rats after a single oral exposure to diesel exhaust particles.
The gastrointestinal route of exposure to particulate matter is important because particles are ingested via contaminated foods and inhaled particles are swallowed when removed from the airways by the mucociliary clearance system. We investigated the effect of an intragastric administration by oral gavage of diesel exhaust particles (DEP) in terms of DNA damage, oxidative stress and DNA repair in colon epithelial cells, liver, and lung of rats. Eight rats per group were exposed to Standard Reference Material 2975 at 0.064 or 0.64 mg/kg bodyweight for 6 and 24 h. Increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine lesions were observed at the highest dose after 6 and 24 h in all three organs. 8-Oxo-7,8-dihydro-2'-deoxyguanosine is repaired by oxoguanine DNA glycosylase 1 (OGG1); upregulation of this repair system was observed as elevated pulmonary OGG1 mRNA levels after 24 h at both doses of DEP, but not in the colon and liver. A general response of the antioxidant defence system is further indicated by elevated levels of heme oxygenase 1 mRNA in the liver and lung 24 h after administration. The level of bulky DNA adducts was increased in liver and lung at both doses after 6 and 24h (DNA adducts in colon epithelium were not investigated). In summary, DEP administered via the gastrointestinal tract at low doses relative to ambient exposure generates DNA damage and increase the expression of defence mechanisms in organs such as the lung and liver. The oral exposure route should be taken into account in risk assessment of particulate matter.
Danielsen
Pernille Høgh
PH
Institute of Public Health, Department of Occupational and Environmental Health, University of Copenhagen, Copenhagen, Denmark.
Risom
Lotte
L
Wallin
Håkan
H
Autrup
Herman
H
Vogel
Ulla
U
Loft
Steffen
S
Møller
Peter
P
D000284:Administration, Oral; D000818:Animals; D003106:Colon / Q000187:drug effects; D018736:DNA Adducts / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D045647:DNA Glycosylases / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008297:Male; D009153:Mutagens / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D052638:Particulate Matter / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species; D001335:Vehicle Emissions / Q000633:toxicity*
D018736:DNA Adducts; D009153:Mutagens; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D001335:Vehicle Emissions; D006419:Heme Oxygenase (Decyclizing); D045647:DNA Glycosylases; C483741:OGG1 protein, rat