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ToxSci Advance Access published online on December 27, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl193
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Performances of the In Vitro Micronucleus Test Compared to the Mouse Lymphoma Assay and the In Vitro Chromosome Aberration Assay

Elisabeth Lorge*,1, Carine Lambert*, Véronique Gervais*, Nathalie Becourt-Lhote*, Jean-Luc Delongeas* and Nancy Claude{dagger}

* Servier Group, Drug Safety Assessment, 45403 Orléans-Gidy, France {dagger} Servier Group, IRIS, 92400 Courbevoie, France

1 Biologie Servier BP 43255, 45403 Fleury-les-Aubrais, France; elisabeth.lorge{at}fr.netgrs.com

Received October 13, 2006; accepted December 13, 2006


  Abstract

The in vitro micronucleus test is commonly used in the early stages of pharmaceutical development as a predictive tool for the regulatory mouse lymphoma assay or in vitro chromosome aberration test. The accumulated data from this assay leads to the suggestion that it could be used as an alternative to the chromosome aberration test or the mouse lymphoma assay in the regulatory genotoxicity battery. In this paper, we present the results of the in vitro micronucleus test on L5178Y mouse lymphoma cells with 25 compounds from Servier research and have compared these results to those obtained in the genotoxicity regulatory battery. All the negative compounds were also negative in the in vitro micronucleus assay. Among the fourteen positive compounds, two of them, positive in the mouse lymphoma assay, were found negative in the in vitro micronucleus test. However, this apparent discordance was likely to be due to cytotoxicity- or high concentration-related false positive responses in the mouse lymphoma assay. In addition, we confirmed that the in vitro micronucleus assay is useful for detecting aneugens, especially when cells in metaphasis and multinucleated cells are also scored, and when cells are allowed to recover after the long treatment. On this series of compounds, the in vitro micronucleus assay showed high sensitivity and possibly a better specificity than the mouse lymphoma assay. Thus, the in vitro micronucleus assay was shown to be at least as adequate as the mouse lymphoma assay or the in vitro chromosome aberration test to be used in the standard genotoxicity battery.

Key Words: Genotoxicity; In vitro tests; In vitro micronucleus assay.


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