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IN VITRO GENOTOXICITY TESTING USING THE MICRONUCLEUS ASSAY IN CELL LINES, HUMAN LYMPHOCYTES AND 3D HUMAN SKIN MODELS.

Kirsch-Volders, Micheline and Elhajouji, Azeddine and Decordier, Ilse and Plas, Gina and Aardema, Marilyn J. and Fenech, Michael (2010) IN VITRO GENOTOXICITY TESTING USING THE MICRONUCLEUS ASSAY IN CELL LINES, HUMAN LYMPHOCYTES AND 3D HUMAN SKIN MODELS. Mutagenesis, 26 (1). pp. 177-184. ISSN 0267-8357

Abstract

The toxicological relevance of the micronucleus (MN) test is well defined: it is a multi-target genotoxic endpoint, assessing not only clastogenic and aneugenic events, but also some epigenetic effects, which is simple to score, accurate, applicable in different celltypes. In addition, it is predictive for cancer, amenable for automation, it allows good extrapolation for potential limits of exposure or thresholds and it is easily measured in experimental both in vitro and in vivo systems. Implementation of in vitro MN (IVMN) assays in the battery of tests for hazard and risk assessment of potential mutagens/carcinogens is therefore fully justified. Moreover, the final draft of its OECD guideline was recently made available. We start this short review by discussing the prerequisites for an acceptable MN assay, including the cell as unit of observation, importance of cell membranes and the requirement of a mitotic or meiotic division and the assessment of cell division in the presence of the test substance. Furthermore, the importance of adequate design of treatment protocols is highlighted and the expected new developments, in particular the in vitro 3D human skin models, are discussed. Finally, we address future research including the possibility of a combined primary 3D human skin and primary human whole blood culture system, and the need for adaptation of the IVMN assays to assess the genotoxic potential of new materials, in particular nanomaterials.

Item Type: Article
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Additional Information: author can archive post-print (ie final draft post-refereeing); Publisher version cannot be used except for Nucleic Acids Research articles
Keywords: Micronucleus test; genotoxicity; Human lymphocytes, cell lines
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Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16
URI: https://oak.novartis.com/id/eprint/3132

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