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Mutagenesis Advance Access originally published online on July 26, 2007
Mutagenesis 2007 22(5):335-342; doi:10.1093/mutage/gem022
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© The Author 2007. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Bioluminescent Salmonella reverse mutation assay: a screen for detecting mutagenicity with high throughput attributes

Jiri Aubrecht*, Jeffery J. Osowski, Prita Persaud, Jennifer R. Cheung, Joel Ackerman, Sarah H. Lopes and Warren W. Ku

Drug Safety Research and Development, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA

Here, we describe the development and evaluation of a novel bioluminescent high-throughput Salmonella reverse mutation assay applicable to the screening of large numbers of small molecules. The bioluminescent Salmonella assay utilizes genetically engineered standard Salmonella tester strains TA98 and TA100 expressing the lux(CDABE) operon from Xenorhabdus luminescence. In principle, the assay employs bioluminescence as a sensor of changes in bacterial metabolism associated with starvation or energy depletion effectively identifying colonies of histidine-independent revertant cells in a high-throughput fashion. The assay provides highly concordant data with the outcome in the standard Salmonella plate incorporation reverse mutation assay. Since the results of the standard Salmonella plate assay are required by various regulatory agencies for approval of new drugs, the bioluminescent Salmonella assay can be effectively used for prioritization of compounds in pharmaceutical drug discovery as well as the evaluation of environmental and industrial chemicals. Because of its high throughput attributes, the assay permits effective, fast and economical screening of a large series of structural analogs enabling the investigation of structure–activity relationships.

* To whom correspondence should be addressed. Tel: 860 715 3384; Fax: 860 715 7884; Email: Jiri_Aubrecht{at}groton.pfizer.com

Received on January 12, 2007; revised on April 26, 2007; accepted on May 10, 2007.


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