Oxidative Stress Generated Damage to DNA by Gastrointestinal Exposure to Insoluble Particles

P.      Moller; J.      K. Folkmann; P.      H. Danielsen; K.      Jantzen; S.      Loft

Abstract

There is growing concern that gastrointestinal exposure to particles is associated with increased risk of toxicity to internal organs and carcinogenicity. The mechanism of action is related to particle-induced oxidative stress and oxidation of DNA. Observations from animal models indicate that gastrointestinal exposure to single-walled carbon nanotubes (SWCNT), fullerenes C₆₀, carbon black, titanium dioxide and diesel exhaust particles generates oxidized DNA base lesions in organs such as the bone marrow, liver and lung. Oral exposure to nanosized carbon black has also been associated with increased level of lipid peroxidation derived exocyclic DNA adducts in the liver, suggesting multiple pathways of oxidative stress for particle-generated damage to DNA. At equal dose, diesel exhaust particles (SRM2975) generated larger levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine in rat liver than carbon black (Printex 90) did, whereas exposure to fullerenes C₆₀ and SWCNT was the least potent. This ranking of samples was also observed for oxidatively damaged DNA in cultured cells. The extent of translocation from the gut is largely unresolved. However, there is evidence indicating that gastrointestinal exposure to particulate matter is associated with oxidative damage to DNA and this might be associated with increased risk of cancer.

Keywords: Comet assay, DFCH assay, DNA damage, nanoparticles, oxidative stress, nanotechnology, pulmonary toxicity, metal oxides, respiratory tract, titanium dioxide, carbon black, inflammation, drug delivery, transcytosis, endocytosis