Oxidatively damaged DNA in rats exposed by oral gavage to C60 fullerenes and single-walled carbon nanotubes.
BACKGROUND
C60 fullerenes and single-walled carbon nanotubes (SWCNT) are projected to be used in medicine and consumer products with potential human exposure. The hazardous effects of these particles are expected to involve oxidative stress with generation of oxidatively damaged DNA that might be the initiating event in the development of cancer.


OBJECTIVE
In this study we investigated the effect of a single oral administration of C60 fullerenes and SWCNT.


METHODS
We measured the level of oxidative damage to DNA as the premutagenic 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in the colon mucosa, liver, and lung of rats after intragastric administration of pristine C60 fullerenes or SWCNT (0.064 or 0.64 mg/kg body weight) suspended in saline solution or corn oil. We investigated the regulation of DNA repair systems toward 8-oxodG in liver and lung tissue.


RESULTS
Both doses of SWCNT increased the levels of 8-oxodG in liver and lung. Administration of C60 fullerenes increased the hepatic level of 8-oxodG, whereas only the high dose generated 8-oxodG in the lung. We detected no effects on 8-oxodG in colon mucosa. Suspension of particles in saline solution or corn oil yielded a similar extent of genotoxicity, whereas corn oil per se generated more genotoxicity than the particles. Although there was increased mRNA expression of 8-oxoguanine DNA glycosylase in the liver of C60 fullerene-treated rats, we found no significant increase in repair activity.


CONCLUSIONS
Oral exposure to low doses of C60 fullerenes and SWCNT is associated with elevated levels of 8-oxodG in the liver and lung, which is likely to be caused by a direct genotoxic ability rather than an inhibition of the DNA repair system.
Folkmann
Janne K
JK
Institute of Public Health, Department of Environmental Health, University of Copenhagen, Copenhagen, Denmark.
Risom
Lotte
L
Jacobsen
Nicklas R
NR
Wallin
Håkan
H
Loft
Steffen
S
Møller
Peter
P
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D045647:DNA Glycosylases / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004337:Drug Carriers / Q000633:toxicity*; D005260:Female; D037741:Fullerenes / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D037742:Nanotubes, Carbon / Q000633:toxicity*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D016133:Polymerase Chain Reaction; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D004337:Drug Carriers; D037741:Fullerenes; D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D045647:DNA Glycosylases; C483741:OGG1 protein, rat; D003849:Deoxyguanosine; C069837:fullerene C60