In Vitro Study of Mutagenesis Induced by Crocidolite-Exposed Alveolar Macrophages NR8383 in Cocultured Big Blue Rat2 Embryonic Fibroblasts
Asbestos-induced mutagenicity in the lung may involve reactive oxygen/nitrogen species (ROS/RNS) released by alveolar macrophages. With the aim of proposing an alternative in vitro mutagenesis test, a coculture system of rat alveolar macrophages (NR8383) and transgenic Big Blue Rat2 embryonic fibrob...
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | Journal of Toxicology |
| Online Access: | http://dx.doi.org/10.1155/2010/323828 |
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| author | Yves Guichard Laurent Gaté Christian Darne Marie-Claire Bottin Cristina Langlais Jean-Claude Micillino Michèle Goutet Schmit Julien Binet Stéphane |
| author_facet | Yves Guichard Laurent Gaté Christian Darne Marie-Claire Bottin Cristina Langlais Jean-Claude Micillino Michèle Goutet Schmit Julien Binet Stéphane |
| author_sort | Yves Guichard |
| collection | DOAJ |
| description | Asbestos-induced mutagenicity in the lung may involve reactive oxygen/nitrogen species (ROS/RNS) released by alveolar macrophages. With the aim of proposing an alternative in vitro mutagenesis test, a coculture system of rat alveolar macrophages (NR8383) and transgenic Big Blue Rat2 embryonic fibroblasts was developed and tested with a crocidolite sample. Crocidolite exposure induced no detectable increase in ROS production from NR8383, contrasting with the oxidative burst that occurred following a brief exposure (1 hour) to zymosan, a known macrophage activator. In separated cocultures, crocidolite and zymosan induced different changes in the gene expressions involved in cellular inflammation in NR8383 and Big Blue. In particular, both particles induced up-regulation of iNOS expression in Big Blue, suggesting the formation of potentially genotoxic nitrogen species. However, crocidolite exposure in separated or mixed cocultures induced no mutagenic effects whereas an increase in Big Blue mutants was detected after exposure to zymosan in mixed cocultures. NR8383 activation by crocidolite is probably insufficient to induce in vitro mutagenic events. The mutagenesis assay based on the coculture of NR8383 and Big Blue cannot be used as an alternative in vitro method to assess the mutagenic properties of asbestos fibres. |
| format | Article |
| id | doaj-art-2f276caf0b5f471bb5b73647a2660f17 |
| institution | OA Journals |
| issn | 1687-8191 1687-8205 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Toxicology |
| spelling | doaj-art-2f276caf0b5f471bb5b73647a2660f172025-08-20T02:08:12ZengWileyJournal of Toxicology1687-81911687-82052010-01-01201010.1155/2010/323828323828In Vitro Study of Mutagenesis Induced by Crocidolite-Exposed Alveolar Macrophages NR8383 in Cocultured Big Blue Rat2 Embryonic FibroblastsYves Guichard0Laurent Gaté1Christian Darne2Marie-Claire Bottin3Cristina Langlais4Jean-Claude Micillino5Michèle Goutet6Schmit Julien7Binet Stéphane8Institut National de Recherche et de Sécurité, rue du Morvan CS 60027, 54519 Vandoeuvre-Les-Nancy Cedex, FranceInstitut National de Recherche et de Sécurité, rue du Morvan CS 60027, 54519 Vandoeuvre-Les-Nancy Cedex, FranceInstitut National de Recherche et de Sécurité, rue du Morvan CS 60027, 54519 Vandoeuvre-Les-Nancy Cedex, FranceInstitut National de Recherche et de Sécurité, rue du Morvan CS 60027, 54519 Vandoeuvre-Les-Nancy Cedex, FranceInstitut National de Recherche et de Sécurité, rue du Morvan CS 60027, 54519 Vandoeuvre-Les-Nancy Cedex, FranceInstitut National de Recherche et de Sécurité, rue du Morvan CS 60027, 54519 Vandoeuvre-Les-Nancy Cedex, FranceInstitut National de Recherche et de Sécurité, rue du Morvan CS 60027, 54519 Vandoeuvre-Les-Nancy Cedex, FranceInstitut National de Recherche et de Sécurité, rue du Morvan CS 60027, 54519 Vandoeuvre-Les-Nancy Cedex, FranceInstitut National de Recherche et de Sécurité, rue du Morvan CS 60027, 54519 Vandoeuvre-Les-Nancy Cedex, FranceAsbestos-induced mutagenicity in the lung may involve reactive oxygen/nitrogen species (ROS/RNS) released by alveolar macrophages. With the aim of proposing an alternative in vitro mutagenesis test, a coculture system of rat alveolar macrophages (NR8383) and transgenic Big Blue Rat2 embryonic fibroblasts was developed and tested with a crocidolite sample. Crocidolite exposure induced no detectable increase in ROS production from NR8383, contrasting with the oxidative burst that occurred following a brief exposure (1 hour) to zymosan, a known macrophage activator. In separated cocultures, crocidolite and zymosan induced different changes in the gene expressions involved in cellular inflammation in NR8383 and Big Blue. In particular, both particles induced up-regulation of iNOS expression in Big Blue, suggesting the formation of potentially genotoxic nitrogen species. However, crocidolite exposure in separated or mixed cocultures induced no mutagenic effects whereas an increase in Big Blue mutants was detected after exposure to zymosan in mixed cocultures. NR8383 activation by crocidolite is probably insufficient to induce in vitro mutagenic events. The mutagenesis assay based on the coculture of NR8383 and Big Blue cannot be used as an alternative in vitro method to assess the mutagenic properties of asbestos fibres.http://dx.doi.org/10.1155/2010/323828 |
| spellingShingle | Yves Guichard Laurent Gaté Christian Darne Marie-Claire Bottin Cristina Langlais Jean-Claude Micillino Michèle Goutet Schmit Julien Binet Stéphane In Vitro Study of Mutagenesis Induced by Crocidolite-Exposed Alveolar Macrophages NR8383 in Cocultured Big Blue Rat2 Embryonic Fibroblasts Journal of Toxicology |
| title | In Vitro Study of Mutagenesis Induced by Crocidolite-Exposed Alveolar Macrophages NR8383 in Cocultured Big Blue Rat2 Embryonic Fibroblasts |
| title_full | In Vitro Study of Mutagenesis Induced by Crocidolite-Exposed Alveolar Macrophages NR8383 in Cocultured Big Blue Rat2 Embryonic Fibroblasts |
| title_fullStr | In Vitro Study of Mutagenesis Induced by Crocidolite-Exposed Alveolar Macrophages NR8383 in Cocultured Big Blue Rat2 Embryonic Fibroblasts |
| title_full_unstemmed | In Vitro Study of Mutagenesis Induced by Crocidolite-Exposed Alveolar Macrophages NR8383 in Cocultured Big Blue Rat2 Embryonic Fibroblasts |
| title_short | In Vitro Study of Mutagenesis Induced by Crocidolite-Exposed Alveolar Macrophages NR8383 in Cocultured Big Blue Rat2 Embryonic Fibroblasts |
| title_sort | in vitro study of mutagenesis induced by crocidolite exposed alveolar macrophages nr8383 in cocultured big blue rat2 embryonic fibroblasts |
| url | http://dx.doi.org/10.1155/2010/323828 |
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