Gene expression profiling to assess the biological effects of manufactured nanomaterials

Abstract

Recently, concern over the influence of manufactured nanoparticles on human health has risen due to advances in the development of nanotechnology. We are interested in the influence of nanoparticles on the pulmonary system at a molecular level. In this study, gene expression profiling of the rat lung after intratracheal instillation or whole-body inhalation exposure to ultrafine nickel oxide(Uf-NiO)particles as a positive control of manufactured nanoparticles such as titanium dioxide, C60 fullerene, carbon nanotube were employed to gain insights into these molecular events. In response to Uf-NiO exposure, there were a large number of highly up-regulated genes associated with the inflammatory response and Mmp12 encoding macrophage metalloelastase 12. These results suggest that Uf-NiO particles lead to acute inflammation immediately after intratracheal instillation or for the inhalation exposure period, and the damaged tissues were repaired in a timedependent manner. Analysis by inductively coupled plasma mass spectrometry and transmission electron microscope revealed that the Uf-NiO particles began to be cleared from the lungs immediately after treatment, and that low levels of the particles were present following exposure. These observations were consistent in gene expression profiling. We conclude that gene expression analysis using DNA microarrays can be extremely useful in assessing the influence of utrafine particles on biological systems.