4.7 Article

Oxidatively Damaged DNA in Rats Exposed by Oral Gavage to C-60 Fullerenes and Single-Walled Carbon Nanotubes

Journal

ENVIRONMENTAL HEALTH PERSPECTIVES
Volume 117, Issue 5, Pages 703-708

Publisher

US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
DOI: 10.1289/ehp.11922

Keywords

DNA damage; DNA repair; nanoparticle; oxidative stress

Funding

  1. Research Centre for Environmental Health
  2. Danish Research Councils
  3. European Union [FP6-012912, 513943]

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BACKGROUND: C-60 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 C-60 fullerenes and SWCNT. METHODS: We measured the level of oxidative damage to DNA as the premuragenic 8-oxo-7,8dihydro-2'-deoxyguanosine (8-oxodG) in the colon mucosa, liver, and lung of rats after intragastric administration of pristine C-60 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 C-60 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 C-60 fullerene-treated rats, we found no significant increase in repair activity. CONCLUSIONS: Oral exposure to low doses of C-60 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.

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