Studies involving indium-containing particles (ICPs) indium phosphide (InP) and indium tin-oxide (ITO) were completed. Studies are in progress to determine if prolonged chronic exposure to sub-lethal concentrations (0.5 and/or 1 M) of soluble InCl3 can transform human lung epithelial (HPL-1D) cells into malignant cancer cells in vitro. The purpose of this carcinogenicity study is based on previous chronic inhalation data in rats and mice showing that InP and ITO particles were highly carcinogenic to the lung combined with the fact that there is currently no cancer data linked to indium exposure in humans. As of week 38, increased expression of matrix metalloproteinases (MMPs) by indium-treated lung cells and morphologic changes suggest that transformation is occurring. Additional assays to examine the acquisition of cancer cell characteristics will include cell proliferation, serum-independent growth, colony formation in soft agar, invasion (using matrigel) and gene expression (using RT-PCR). The NTP is also running a micronucleus assay and Ames test to assess the genotoxicity of InCl3.

Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
2015
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
Zip Code
Gwinn, William M; Qu, Wei; Bousquet, Ronald W et al. (2015) Macrophage solubilization and cytotoxicity of indium-containing particles as in vitro correlates to pulmonary toxicity in vivo. Toxicol Sci 144:17-26
Kelly, Francine L; Sun, Jesse; Fischer, Bernard M et al. (2014) Diacetyl induces amphiregulin shedding in pulmonary epithelial cells and in experimental bronchiolitis obliterans. Am J Respir Cell Mol Biol 51:568-74
Gwinn, William M; Qu, Wei; Shines, Cassandra J et al. (2013) Macrophage Solubilization and Cytotoxicity of Indium-Containing Particles In Vitro. Toxicol Sci :
Morgan, Daniel L; Nyska, Abraham; Harbo, Sam Jens et al. (2011) Multisite carcinogenicity and respiratory toxicity of inhaled 1-bromopropane in rats and mice. Toxicol Pathol 39:938-48
Palmer, Scott M; Flake, Gordon P; Kelly, Fran L et al. (2011) Severe airway epithelial injury, aberrant repair and bronchiolitis obliterans develops after diacetyl instillation in rats. PLoS One 6:e17644
Mathews, James M; Watson, Scott L; Snyder, Rodney W et al. (2010) Reaction of the butter flavorant diacetyl (2,3-butanedione) with N-?-acetylarginine: a model for epitope formation with pulmonary proteins in the etiology of obliterative bronchiolitis. J Agric Food Chem 58:12761-8
Card, Jeffrey W; Carey, Michelle A; Voltz, James W et al. (2010) Modulation of allergic airway inflammation by the oral pathogen Porphyromonas gingivalis. Infect Immun 78:2488-96
Anderson, Stacey E; Munson, Albert E; Butterworth, Leon F et al. (2010) Whole-body inhalation exposure to 1-bromopropane suppresses the IgM response to sheep red blood cells in female B6C3F1 mice and Fisher 344/N rats. Inhal Toxicol 22:125-32
Kirby, Patrick J; Shines, Cassandra J; Taylor, Genie J et al. (2009) Pleural effects of indium phosphide in B6C3F1 mice: nonfibrous particulate induced pleural fibrosis. Exp Lung Res 35:858-82