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Methods for Using the Mouse Lymphoma Assay to Screen for Chemical Mutagenicity and Photo-Mutagenicity

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Optimization in Drug Discovery

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

The mouse lymphoma assay (MLA) quantifies genetic alterations affecting expression of the thymidine kinase (Tk) gene which is located on chromosome 11. This assay is widely used for evaluating the genotoxic potential of various agents. It can also be used for photo-mutagenicity. The Tk-deficient mutants in the MLA result not only from point mutations but also from gross structural and numerical changes at the chromosomal level. The MLA has been recommended as one component of the genotoxicity test battery in many regulatory authorities, countries, and international organizations. The protocol for the MLA has been optimized and adopted by many laboratories around the world. In this chapter, the authors provide an example of the application of the MLA by detailing the procedures that are used for performing the assay in their laboratory and analyzing and interpreting the data generated from both the soft-agar and microwell versions of the assay. In addition, they provide information for using the assay for the analysis of potential photo-mutagenicity.

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Acknowledgements

The authors thank Drs. Mugimane G. Manjanatha and Haixia Lin for the critical review of the manuscript. Use of trade names is for informational purposes only and in no way implies endorsement by the U.S. Food and Drug Administration (FDA). The views presented in this paper do not necessarily reflect those of the U.S. FDA.

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Authors and Affiliations

  1. Division of Genetic and Molecular Toxicology, National Center for Toxicological Research (NCTR), Food and Drug Administration (FDA), Jefferson, AR, USA

    Nan Mei, Xiaoqing Guo & Martha M. Moore

Authors
  1. Nan Mei
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  2. Xiaoqing Guo
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  3. Martha M. Moore
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Editors and Affiliations

  1. CREATe Core Science Technologies, Janssen Research & Development, LLC, Spring House, Pennsylvania, USA

    Gary W. Caldwell

  2. CREATe Core Science Technologies, Janssen Research & Development, LLC, Spring House, Pennsylvania, USA

    Zhengyin Yan

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Mei, N., Guo, X., Moore, M.M. (2014). Methods for Using the Mouse Lymphoma Assay to Screen for Chemical Mutagenicity and Photo-Mutagenicity. In: Caldwell, G., Yan, Z. (eds) Optimization in Drug Discovery. Methods in Pharmacology and Toxicology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-742-6_34

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  • DOI: https://doi.org/10.1007/978-1-62703-742-6_34

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-741-9

  • Online ISBN: 978-1-62703-742-6

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