Mechanisms of fiber-induced genotoxicity.
The mechanisms of particle-induced genotoxicity have been investigated mainly with asbestos fibers. The results are summarized and discussed in this paper. DNA damage can be produced by oxidoreduction processes generated by fibers. The extent of damage yield depends on experimental conditions: if iron is present, either on fibers or in the medium, damage is increased. However, iron reactivity does not explain all the results obtained in cell-free systems, as breakage of plasmid DNA was not directly associated with the amount of iron released by the fibers. The proximity of DNA to the site of generation of reactive oxygen species (ROS) is important because these species have an extremely short half-life. Damage to cellular DNA can be produced by oxidoreduction processes that originate from cells during phagocytosis. Secondary molecules that are more stable than ROS are probably involved in DNA damage. Oxidoreduction reactions originating from cells can induce mutations. Genotoxicity is also demonstrated by chromosomal damage associated with impaired mitosis, as evidenced by chromosome missegregation, spindle changes, alteration of cell cycle progression, formation of aneuploid and polyploid cells, and nuclear disruption. In some of these processes, the particle state and fiber dimensions are considered important parameters in the generation of genotoxic effects.
Jaurand
M C
MC
Institut Mondor de Médecine Moléculaire IM3, Faculté de Médecine, INSERM Unité 139, Créteil, France. jaurand@im3.inserm.fr
D000818:Animals; D001194:Asbestos / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D004249:DNA Damage / Q000187:drug effects; D006801:Humans; D019016:Mineral Fibers / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*
D002273:Carcinogens; D019016:Mineral Fibers; D009153:Mutagens; D001194:Asbestos