In vivo Analysis of Hazard Mechanism reveals Long-fibre Carbon Nanotubes induce Pleural Mesothelioma via Silencing and/or Loss of Key Tumour Suppressor Genes

Marion MacFarlane

Exposure to asbestos fibres causes pathological changes in the pleural cavity including malignant mesothelioma.  Length-dependent retention of asbestos fibres in the pleural cavity is crucial for disease development.  Chronic inflammation plays a key role in carcinogenesis and epigenetic events, rather than driver mutations, are considered to be major causative factors.  Engineered carbon nanotubes (CNT) are similar to asbestos in terms of their high aspect-ratio (HAR) and thus may pose an asbestos-like inhalation hazard, however the molecular mechanisms underlying their carcinogenic potential have not been fully explored. We show that pleural exposure of mice to Long-fibre carbon nanotubes mimics exposure to asbestos, from initial and chronic inflammation, through loss of the same tumour-suppressor genes and eventual sporadic development of malignant mesothelioma. Thus, HAR nanomaterials of a similar nature may pose an asbestos-like inhalation hazard.

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