National Nanomedicine Seminar - "Recent Advances in the Knowledge Base of Nanotoxicology: Pulmonary Responses to Carbon Nanotubes"
Vincent Castranova, Ph.D.
Department of Pharmaceutical Sciences, West Virginia University
Recent Advances in the Knowledge Base of Nanotoxicology: Pulmonary Responses to Carbon Nanotubes
Carbon nanotube applications in structural materials, electronics, and medicine are expanding rapidly, leading to potential occupational exposure. Fifteen years ago, concern was raised that high aspect ratio durable CNTs may act as asbestos to cause pulmonary disease. Numerous studies have since shown that CNTs cause lung inflammation/damage, granulomas (due to CNT agglomerates), and fibrosis (due to deposition of smaller CNT structures in the distal lung). Although these pulmonary responses maybe asbestos-like, CNT pathogenesis differs from asbestos; i.e., 1) asbestos causes frustrated phagocytosis and persistent inflammation, while CNTs does not; 2) purified CNTs do not generate radicals as does asbestos; and 3) lung gene expression pathways differ for MWCNTs vs. asbestos. Indeed, the fibrogenic potency of CNTs appears driven by their ability to enter the alveolar interstitium and directly activate fibroblast proliferation and collagen production. Fibrogenic potential is SWCNTs > MWCNTs > CNFs = asbestos. Carboxylation of MWCNTs decreases fibrotic potency, while amination enhances bioactivity. These pulmonary responses to CNTs are qualitatively similar in mice vs. rats and quantitatively similar in males vs. females. Recent results also indicate that MWCNTs can both initiate and promote lung cancer, with male rats being more susceptible to MWCNT-induced lung tumors than female rats. MWCNTs can migrate to the interpleural space, and after two years of inhalation exposure MWCNT-induced mesothelial hyperplasia was reported. However, to date, no mesothelioma has been demonstrated following pulmonary exposure to MWCNTs.
Pulmonary exposure to MWCNTs has also been reported to adversely affect cardiac performance and microvascular function. Lung sensory neurons in the lung are involved in this response. Therefore, recent expansion of nanotoxicology data allows for risk analysis for CNTs.
Tuesday, December 11, 2018 at 3:25pm
121 Snell Library