The Salmonella Mutagenicity Assay: The Stethoscope of Genetic Toxicology for the 21st Century

• Published in: Environmental health perspectives Vol. 118; no. 11; pp. 1515 - 1522
• Main Authors: Claxton, Larry D., de A. Umbuzeiro, Gisela, DeMarini, David M.
• Format: Journal Article
• Language: English
• Published: Research Triangle Park, NC National Institute of Environmental Health Sciences 01.11.2010; US Department of Health and Human Services
• Subjects: Assaying; Bacterial diseases; Bacterial diseases of the digestive system and abdomen; Bacterial genetics; Biological and medical sciences; Biological Assay - methods; Carcinogenesis; Carcinogenicity; Carcinogens; Chemical hazards; Environment. Living conditions; Environmental health; General aspects. Methods; Genetic aspects; Genetic toxicology; Genetics; Genotoxicity; Health aspects; Human bacterial diseases; In vitro testing; Infectious diseases; Mathematical models; Medical sciences; Microsomes - drug effects; Mutagenesis; Mutagenicity; Mutagenicity Tests - methods; Mutagens; Mutagens - toxicity; Public health. Hygiene; Public health. Hygiene-occupational medicine; Review; Reviews; Rodents; Salmonella; Salmonella - drug effects; Salmonella - genetics; Stethoscopes; Toxicology; United States; 21st century toxicology; Salmonella; Century 21st; Sulmonella mutagenicity assay; Mutagenicity testing; Toxicity; Ames assay; Tumorigenicity; carcinogenicity; Infection; Toxicology; Health and environment; Salmonella assay; high-throughput assays; Bacteriosis; Bacteria; Genetics; Salmonellosis; genetic toxicology; Enterobacteriaceae
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.1002336

OBJECTIVES: According to the 2007 National Research Council report Toxicology for the Twenty-First Century, modern methods (e.g., "omics," in vitro assays, high-throughput testing, computational methods) will lead to the emergence of a new approach to toxicology. The Salmonell. 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 two paradigm shifts: that some carcinogens were mutagens and that some environmental samples (e.g., air, water, soil, food, combustion emissions) were mutagenic. Although there are > 10,000 publications on the Salmonella assay a covering tens of thousands of agents, data on even more agents probably exist in unpublished form, largely as proprietary studies by industry. The Salmonell. 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 structure—activity analysis. CONCLUSIONS: Similar to a stethoscope as a first-line, inexpensive tool in medicine, the Salmonell. assay can serve a similar, indispensable role in the foreseeable future of 21st century toxicology.