Biological activities of asbestos and other mineral fibres

The mechanisms of asbestos carcinogenesis are related largely to the chronic inflammatory response to these fibres when they are lodged in tissues. Mesothelial cells are much more susceptible than other cell types to asbestos and thus individuals exposed to asbestos characteristically develop malignant mesothelioma (MM). The chronic inflammatory response is driven by the release of high mobility group box 1 protein (HMGB1) in the extracellular space by mesothelial cells and by inflammatory cells undergoing programmed cell necrosis caused by asbestos. Genetics influences the individual response to asbestos, and thus individual susceptibility to asbestos carcinogenesis varies. HMGB1 represents a promising biomarker of asbestos exposure to MM and strategies aimed at interfering with HMGB1 and chronic inflammation may help prevent/delay the onset of MM in individuals exposed to asbestos or other carcinogenic fibres. Individuals carrying germline BAP1 mutations can develop any type of cancer, includingMM, regardless of asbestos exposure. However, animal experiments suggest that these individuals are also more susceptible to asbestos carcinogenesis, even at low exposure levels, compared to the population at large.