Effets cellulaires et moléculaires de l'amiante

Abstract

L' interaction entre les fibres d' amiante et differents types cellulaires est suivie, in vitro et in vivo, d' une phagocytose. Parallelement, on observe une activation de certains facteurs de transcription, ainsi que de la voie de signalisation impliquant la PKC pour certains types cellulaires. Sur des cellules en division, l' amiante provoque des anomalies mitotiques (segregation anormale des chromosomes, aneuploidie, micronoyaux, bi/multinucleation), du fait d' interferences au cours de la segregation chromosomique. De plus, les fibres provoquent une activation de points de controle du cycle cellulaire compatible avec l' existence de lesions sur l' ADN, et un arret du cycle cellulaire. L' amiante est capable d' induire des lesions de l' ADN et des mutations. La cause de ces alterations semble etre en partie la production d' especes actives derivees de l' oxygene (EADO). L' origine de ces molecules peut etre double : production directe par certains types de fibres et/ou reponse cellulaire aux fibres (phagocytose, reaction inflammatoire). Compte tenu de l' utilisation actuelle de fibres minerales artificielles, notamment pour remplacer l' amiante, la connaissance plus approfondie de ces mecanismes d' action moleculaire reste une priorite en toxicologie de l' environnement.

Elucidating the mechanisms of asbestos-induced toxicity is of paramount interest for 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 segragating 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 and 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 fibers during phagocytosis and inflammatory events. These scenarios are postulates that have developed from recent studies showing DNA base hydroxylation and activation of DNA repair pathways in asbestos-exposed cells. The current use 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. [References: 53]