title: In vitro comet and micronucleus assays do not predict morphological transforming effects of silica particles in Syrian Hamster Embryo cells.
abstract: Crystalline silica particles and asbestos have both been classified as carcinogenic by the International Agency for Research on Cancer (IARC). However, because of the limited data available, amorphous silica was not classifiable. In vitro, the carcinogenic potential of natural crystalline and amorphous silica particles has been revealed by the Syrian Hamster Embryo (SHE) cell transformation assay. On the other hand, the genotoxic potential of those substances has not been investigated in SHE cells. And yet, genotoxicity assays are commonly used for hazard evaluation and they are often used as in vitro assays of reference to predict a possible carcinogenic potential. The main objective of this study was to compare the genotoxic potential and the carcinogenic potential of different crystalline and amorphous silica particles in SHE cells. Three silica samples of different crystallinity were used: natural amorphous silica, partially crystallized silica and quartz silica particles. Their genotoxicity were tested through the in vitro micronucleus assay and the comet assay in SHE, and their carcinogenic potential through the SHE transformation assay. In addition, silica samples were also tested with the same genotoxicity assays in V79 hamster-lung cells, a common in vitro model for particle exposure. Results obtained in the micronucleus and the comet assays show that none of the silica was capable of inducing genotoxic effects in SHE cells and only the amorphous silica induced genotoxic effects in V79 cells. However in the SHE cell transformation assays, the partially crystallized and quartz silica were able to induce morphological cell transformation. Together, these data suggest that, in vitro, the short-term genotoxic assays alone are not sufficient to predict the hazard and the carcinogenic potential of this type of particles; SHE transformation assay appears a more reliable tool for this purpose and should be included in the "in vitro battery assays" for hazard assessment.
authors.affiliation: Département Toxicologie et Biométrologie, Institut National de Recherche et de Sécurité (INRS), Rue du Morvan, CS 60027, 54519 Vandoeuvre Les Nancy Cedex, France. Electronic address: christian.darne@inrs.fr.
authors.forename: Christian
authors.initials: C
authors.lastname: Darne
authors.affiliation: Département Toxicologie et Biométrologie, Institut National de Recherche et de Sécurité (INRS), Rue du Morvan, CS 60027, 54519 Vandoeuvre Les Nancy Cedex, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Coulais
authors.affiliation: Département Toxicologie et Biométrologie, Institut National de Recherche et de Sécurité (INRS), Rue du Morvan, CS 60027, 54519 Vandoeuvre Les Nancy Cedex, France.
authors.forename: Francine
authors.initials: F
authors.lastname: Terzetti
authors.affiliation: Département Toxicologie et Biométrologie, Institut National de Recherche et de Sécurité (INRS), Rue du Morvan, CS 60027, 54519 Vandoeuvre Les Nancy Cedex, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Fontana
authors.affiliation: Département Toxicologie et Biométrologie, Institut National de Recherche et de Sécurité (INRS), Rue du Morvan, CS 60027, 54519 Vandoeuvre Les Nancy Cedex, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Binet
authors.affiliation: Département Toxicologie et Biométrologie, Institut National de Recherche et de Sécurité (INRS), Rue du Morvan, CS 60027, 54519 Vandoeuvre Les Nancy Cedex, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Gaté
authors.affiliation: Département Toxicologie et Biométrologie, Institut National de Recherche et de Sécurité (INRS), Rue du Morvan, CS 60027, 54519 Vandoeuvre Les Nancy Cedex, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Guichard
mesh_terms: D000818:Animals; D017632:Asbestos, Serpentine / Q000737:chemistry / Q000633:toxicity; D002273:Carcinogens / Q000737:chemistry / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002478:Cells, Cultured; D055598:Chemical Phenomena; D003001:Cloning, Molecular; D020552:Comet Assay / Q000379:methods*; D006224:Cricetinae / Q000196:embryology; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D015162:Micronucleus Tests / Q000379:methods*; D010316:Particle Size; D012822:Silicon Dioxide / Q000737:chemistry / Q000633:toxicity*; D014961:X-Ray Diffraction
chemical_list: D017632:Asbestos, Serpentine; D002273:Carcinogens; D012822:Silicon Dioxide
keywords: Asbestos; Genotoxicity; In vitro comet assay; In vitro micronucleus assay; SHE cell transformation; Silica