Transcriptomic responses to crystalline silica exposure.
Joseph-P; Umbright-C; Sellamuthu-R
Inhalation toxicology, third edition. Salem H, Katz SA, eds. Boca Raton, FL: CRC Press, 2014 Aug; :423-458
Transcriptomics responses to crystalline silica exposure: Crystalline silica particles, following their entry into the lungs, are phagocytosed by the alveolar macrophages (AMs) for elimination. In the absence of efficient elimination from the lungs, such as under conditions of excessive crystalline silica exposure, interaction with the inhaled silica particles activates the AMs resulting in AM death and release of the silica particles and various signaling molecules within the lungs. The crystalline silica particles as well as the signaling molecules released into the lungs may interact with the alveolar epithelium to initiate a cascade of pulmonary and extra-pulmonary events. The net result is the recruitment of inflammatory cells into the lungs, release of toxic reactive oxygen and nitrogen species, the induction of inflammation, DNA damage, and fibrosis leading to the development of diseases, for example, silicosis and cancer. Normal functioning of cells/tissues/organs is regulated by the expression of a large number of genes that are organized as specific biological functions, pathways, and networks. The crystalline silica particles as well as the various signaling molecules released from activated AMs may cause alterations in the expression of one or several genes to result in the functional disruption of the corresponding biological functions, pathways and networks that are vital for normal cell/tissue/organ function. In addition, the transcriptome may be affected as a secondary effect of the pulmonary toxicity resulting from the inhaled crystalline silica particles. Therefore, global gene expression profiling of biological samples that are exposed to crystalline silica and functional analysis of the genes differentially expressed in response to the exposure may provide valuable information with respect to the toxicity potential of silica as well as the underlying molecular mechanisms of crystalline silicainduced pulmonary and extra-pulmonary toxicity.
Silicates; Silicosis; Silica-dusts; Exposure-levels; Hazards; Risk-factors; Lung; Lung-disease; Particulates; Particulate-dust; Molecular-structure; Molecular-biology; Respiratory-system-disorders; Pulmonary-function; Pulmonary-system; Pulmonary-system-disorders; Diseases; Cancer; Cell-biology; Cell-damage; Cell-function; Cellular-function; Genes; Biological-function; Toxins; Toxic-effects
Inhalation toxicology, third edition