Environmental Health Perspectives 105, Supplement 5, September 1997: Article by Jaurand

Environmental Health Perspectives 105, Supplement 5, September 1997

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Mechanisms of Fiber-induced Genotoxicity

Marie-Claude Jaurand

Institut Mondor de Médecine Moléculaire IM3, Faculté de Médecine, INSERM Unité 139, Créteil, France

Abstract
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. -- Environ Health Perspect 105(Suppl 5):1073-1084 (1997)

Key words : asbestos, genotoxicity, in vitro cell systems, lung cancer, man-made fibers, mechanisms of action, mesothelioma

This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York. Manuscript received at EHP 26 March 1997; accepted 9 April 1997.

Address correspondence to Dr. M.-C. Jaurand, Institut Mondor de Médecine Moléculaire IM3, Faculté de Médecine, INSERM Unité 139, 8, rue du Général Sarrail, 94010 Créteil Cedex, France. Telephone: 33 1 49 81 36 56. Fax: 33 1 49 81 35 33. E-mail: jaurand@im3.inserm.fr

Abbreviations used: CH, Chinese hamster; CHO, Chinese hamster ovary; DF, desferrioxamine; 8-OHdG, 8-hydroxydeoxyguanosine; HGPRT, hypoxanthine guanine phosphoribosyl transferase; HMC, human mesothelial cells; H ₂ O ₂ , hydrogen peroxide; LOH, loss of heterozygosity; MMMF, man-made mineral fiber(s); MMVF, man-made vitreous fiber(s); OH ^· , hydroxyl radical; RCF, refractory ceramic fiber; ROS, reactive oxygen species; SHE, Syrian hamster embryo.

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Last Update: December 1, 1997