Promotion of lung adenocarcinoma following inhalation exposure to multi-walled carbon nanotubes

Linda M Sargent, Dale W Porter, Lauren M Staska, Ann F Hubbs, David T Lowry, Lori Battelli, Katelyn J Siegrist, Michael L Kashon, Robert R Mercer, Alison K Bauer, Bean T Chen, Jeffrey L Salisbury, David Frazer, Walter McKinney, Michael Andrew, Shuji Tsuruoka, Morinobu Endo, Kara L Fluharty, Vince Castranova, Steven H Reynolds

Engineered carbon nanotubes are currently used in many consumer and industrial products such as paints, sunscreens, cosmetics, toiletries, electronic processes and industrial lubricants. Carbon nanotubes are among the more widely used nanoparticles and come in two major commercial forms, single-walled carbon nanotubes (SWCNT) and the more rigid, multi-walled carbon nanotubes (MWCNT). The low density and small size of these particles makes respiratory exposures likely. Many of the potential health hazards have not been investigated, including their potential for carcinogenicity. We, therefore, utilized a two stage initiation/promotion protocol to determine whether inhaled MWCNT act as a complete carcinogen and/or promote the growth of cells with existing DNA damage. Six week old, male, B6C3F1 mice received a single intraperitoneal (ip) injection of either the initiator methylcholanthrene(MCA, 10 μg/g BW, i.p.), or vehicle (corn oil). One week after i.p. injections, mice were exposed by inhalation to MWCNT (5 mg/m³, 5 hours/day, 5 days/week) or filtered air (controls) for a total of 15 days. At 17 months post-exposure, mice were euthanized and examined for lung tumor formation.