Inflammatory response, reactive oxygen species production and DNA damage in mice after intrapleural exposure to carbon nanotubes.

Abstract

Carbon nanotubes (CNTs) are speculated to cause mesothelioma by persistent inflammation, oxidative stress, tissue injury and genotoxicity. To investigate pleural response to CNTs, we exposed C57BL/6 mice by intrapleural injection of 0.2 or 5\u2009µg multi-walled CNTs (MWCNT-7, NM-401 and NM-403) or single-walled CNTs (NM-411). Inflammatory response, cellular reactive oxygen species (ROS) production of pleural lavage cells and genotoxicity in cells from the mesothelial surface were assessed at day 1 and 90 after the exposure. Long and rigid types of MWCNTs (MWCNT-7 and NM-401) caused acute inflammation, characterized by influx of macrophages, neutrophils and eosinophils into the pleural cavity. The inflammation was still evident at 90\u2009days after the exposure, although it had reduced dramatically. The cellular ROS production was increased at day 90 after the exposure to MWCNT-7 and NM-401. The short and tangled type of MWCNT (i.e. NM-403) did not cause pleural inflammation or ROS production in pleural fluid cells. The exposure to NM-411 did not cause consistent inflammation responses or cellular ROS production. Levels of DNA strand breaks and DNA oxidation damage were unaltered, except for NM-411-exposed mice that had increased level of DNA strand breaks at 90\u2009days after the exposure. In conclusion, the long and rigid CNTs caused prolonged inflammatory response and increased ROS production in pleural lavage cells, yet it was not reflected in higher levels of DNA damage in pleural tissue.