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Mutagenesis Advance Access published online on May 17, 2005

Mutagenesis, doi:10.1093/mutage/gei033
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© The Author 2005. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please email: journals.permissions@oupjournals.org
Received March 17, 2005
Revised April 20, 2005
Accepted April 20, 2005

Review

The in vivo comet assay: use and status in genotoxicity testing

Susanne Brendler-Schwaab 1, Andreas Hartmann 2, Stefan Pfuhler 3, and Günter Speit 4*

1 Federal Institute for Drugs and Medical Devices, Bonn, Germany
2 Novartis Pharma AG, Basel, Switzerland
3 Wella AG, Darmstadt, Germany
4 Universität Ulm, Abteilung Humangenetik, D-89069, Ulm, Germany

* To whom correspondence should be addressed.
Günter Speit, E-mail: guenter.speit{at}medizin.uni-ulm.de


   Abstract

The in vivo comet assay (single cell gel electrophoresis assay) in its alkaline version (pH >13) is being increasingly used in genotoxicity testing of substances such as industrial chemicals, biocides, agrochemicals, food additives and pharmaceuticals. Recommendations for an appropriate performance of the test using OECD guidelines for other in vivo genotoxicity tests have been published. In this review, we critically discuss the biological significance of comet assay effects in general and the status of the test in current strategies for genotoxicity testing. Examples for practical applications of the in vivo comet assay and potential consequences of positive and negative test results are given. The significance of comet assay results for hazard identification and risk assessment is discussed. In accordance with international guidelines for genotoxicity testing the in vivo comet assay is recommended for follow-up testing of positive in vitro findings. It is particularly useful as a tool for the evaluation of local genotoxicity, especially for organs/cell types which cannot easily be evaluated with other standard tests. A positive result in an appropriately performed in vivo comet assay indicates genotoxicity of the test compound in the tissue tested and gains particular significance when a mutagenic potential of the test compound has already been demonstrated in vitro. Such findings will have practical consequences in the risk assessment processes and further development of substances.


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