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The Salmonella Mutagenicity Assay: The Stethoscope of Genetic Toxicology for the 21 st Century
CLAXTON, L. D., G. UMBUZEIRO, AND D. M. DEMARINI. The Salmonella Mutagenicity Assay: The Stethoscope of Genetic Toxicology for the 21 st Century. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 118(11):1515-1522, (2010).
This study shows the procedures that occurred to validate and develop the Salmonella mutagenicity assay into the versatile, indispensable toxicology assay it is today--and how many of those procedures will need to be applied to the development of selected high-throughput in vitro toxicity assays in the 21 st century
OBJECTIVES: According to the 2007 National Research Council report Toxicology for the Twenty-first Century, modem methods ("omics," in vitro assays, high-throughput testing, computational methods, etc.) will lead to the emergence of a new approach to toxicology. The Salmonella mammalian microsome mutagenicity assay has been central to the field of genetic toxicology since the 1970s. Here we document the paradigm shifts engendered by the assay, the validation and applications of the assay, and how the assay is a model for future in vitro toxicology assays. DATA SOURCES: We searched PubMed®, Scopus", and Web of Knowledge" using key words relevant to the Salmonella assay and additional genotoxicity assays. DATA EXTRACTION: We merged the citations, removing duplicates, and categorized the papers by year and topic. DATA SYNTHESIS: The Salmonella assay led to 2 paradigm shifts: that some carcinogens were mutagens and that some samples of air, water, soil, food, combustion emissions, etc. were mutagenic. Although there are >10,000 publications on the Salmonella assay, covering tens of thousands of agents, data on even more agents likely exist in unpublished form, largely as proprietary studies by industry. The Salmonella assay is a model for the development of 21st century in vitro toxicology assays in terms of the establishment of standard procedures, ability to test various agents, transferability across laboratories, validation and testing, and structureactivity analysis. CONCLUSIONS: Similar to a stethoscope as a first-line, inexpensive tool in medicine, the Salmonella assay can serve a similar, indispensable role in the foreseeable future of 21st century toxicology.