ABSTRACT
Asbestos “bers initiate variable effects in mesothelial cells and lung mesenchymal and epithelial cells, the target cells of malignant mesothelioma, asbestosis, and lung cancer.1,2 The effects mediated by the different types of asbestos are dependent on “ber shape (and size) as well as the chemistry of the “bers. Especially, the surface composition of “bers plays an important role, with many effects mediated by iron either as an integral part of the “ber or as an impurity on its surface. Some effects are purely mechanical, whereas others are mediated via direct interactions of asbestos “bers with cell components, such as receptors, and via generation of reactive oxygen species (ROS). All result in the alteration of cell signaling pathways that regulate gene expression or regulatory
CONTENTS
4.1 Introduction .......................................................................................................................... 109 4.2 The Limitations of Experimental Models and Their Applicability to Human Exposures ........ 110 4.3 Apoptosis: Friend or Foe? ..................................................................................................... 113
4.3.1 The Role of Apoptosis in the Development of Fibrosis and Malignancies .............. 114 4.3.2 The Role of Apoptosis: Malignant Neoplasia ........................................................... 114
4.4 Direct Cellular Events after Inhalation of Asbestos ............................................................. 115 4.4.1 Reactive Oxygen Species .......................................................................................... 116
4.5 Oxidative Stress and In¸ammatory Responses .................................................................... 117 4.5.1 Antioxidants and the Role of the Extracellular Matrix ............................................ 117 4.5.2 Activation of Transcription Pathways ....................................................................... 119 4.5.3 Activation of Growth Factors and the Role of TNF-α...............................................119 4.5.4 TGF-β and Asbestos-Related Diseases .................................................................... 120
4.6 Synergistic Effects with Other Toxins .................................................................................. 122 4.7 Other Factors of Interest ....................................................................................................... 122
4.7.1 Mutations .................................................................................................................. 122 4.7.2 Host Factors .............................................................................................................. 122
4.8 Summary ..............................................................................................................................124 References ......................................................................................................................................124
