Cellular And Molecular Effects Of Asbestos

Elucidating the mechanisms of asbestos-induced toxicity is of paramount interest fbr scientific and economic reasons. When asbestos fibers interact with a variety of cell types, in vivo and in vitro, including pleural mesothelial cells that specifically respond to asbestos, phagocytosis ensues. Concomitant with this response is an activation of several transcription factors, and certain cell types also exhibit an activation of a PKC signaling pathway from cell surface receptors. Asbestos in dividing cells causes mitotic abnormalities such as aneuploidy, micronuclei and multinucleated cells by physically interfering with segregating chromosomes. In addition, asbestos fibers activate cell cycle control mechanisms consistent with the development of DNA damage. Asbestos fibers cause DNA lesions and mutations that can lead to cancer, nd this damage may be partly related to the production of reactive oxygen species (ROS). ROS can originate from direct production by some fiber types as well as from cellular responses to the fiber's during phagocytosis and inflammatory events. These scenarios are postulates that have developed fi-om recent studies showing DNA base hydroxylation and activation of DNA repair pathways in asbestos-exposed cells. The current we of man-made mineral fibers, partly as asbestos substitutes, requires that we develop a thorough knowledge of the mechanisms through which fibers induce genetic abnormalities. This effort is a. priority for molecular toxicologists studying environmental insults.