Oxidative DNA damage in the rat lung induced by intratracheal instillation and inhalation of nanoparticles

Abstract

Nanoparticles are widely used as useful industrial materials. Therefore, their possible adverse health effects must be appraised. We assessed and compared the oxidative DNA damage caused by four different nanoparticles (TiO₂, NiO, ZnO and CeO₂). The effects of the administration methods, intratracheal instillation and inhalation, were also evaluated. Rats were subjected to intratracheal instillations or 4 weeks of inhalation exposure to the nanoparticles, and the 8-hydroxydeoxyguanosine (8-OHdG) levels in the lung were analyzed by an HPLC-EC detector method. The 8-OHdG levels were increased in a dose-dependent manner with the inhalation of NiO. ZnO also increased the 8-OHdG levels with inhalation. In comparison with the control, the 8-OHdG levels were significantly and persistently higher with the CeO₂ nanoparticle administration, by both intratracheal instillation and inhalation. In contrast, there were no significant differences in the 8-OHdG levels between the control and TiO₂ nanoparticle-treated groups, with either intratracheal instillation or inhalation during the observation period. These results indicated that NiO, ZnO and CeO₂ nanoparticles generate significant amounts of free radicals, and oxidative stress may be responsible for the lung injury caused by these nanoparticles. In addition, both intratracheal instillation and inhalation exposure induced similar tendencies of oxidative DNA damage with these nanoparticles.