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Genetic toxicology in the 21st century: Reflections and future directions
MAHADEVAN, B., R. D. SNYDER, M. D. WATERS, R. D. BENZ, R. A. KEMPER, R. R. TICE, AND A. M. RICHARD. Genetic toxicology in the 21st century: Reflections and future directions. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS. Wiley Liss, New York, NY, 52(5):339 - 354, (2011).
Can genetic toxicology testing in the chemical or pharmaceutical industry rise above the suspicion that it may have limited utility and relevance with regard to human cancer risk? We will briefly examine where we are and where we should or could be headed, to set the stage for a broader discussion of these topics in the following pages. The remaining sections were contributed by presenters in a symposium entitled ‘‘Genetic Toxicology in the 21st Century’’ at the EMS 40th annual meeting held from October 24–29, 2009 in St. Louis, Missouri.
A symposium at the 40th anniversary of the Environmental Mutagen Society, held from October 24–28, 2009 in St. Louis, MO, surveyed the current status and future directions of genetic toxicology. This article summarizes the presentations and provides a perspective on the future. An abbreviated history is presented, highlighting the current standard battery of genotoxicity assays and persistent challenges. Application of computational toxicology to safety testing within a regulatory setting is discussed as a means for reducing the need for animal testing and human clinical trials, and current approaches and applications of in silico genotoxicity screening approaches across the pharmaceutical industry were surveyed and are reported here. The expanded use of toxicogenomics to illuminate mechanisms and bridge genotoxicity and carcinogenicity, and new public efforts to use high-throughput screening technologies to address lack of toxicity evaluation for the backlog of thousands of industrial chemicals in the environment are detailed. The Tox21 project involves coordinated efforts of four U.S. Government regulatory/research entities to use new and innovative assays to characterize key steps in toxicity pathways, including genotoxic and nongenotoxic mechanisms for carcinogenesis. Progress to date, highlighting preliminary test results from the National Toxicology Program is summarized. Finally, an overview is presented of ToxCast™, a related research program of the U.S. Environmental Protection Agency, using a broad array of high throughput and high content technologies for toxicity profiling of environmental chemicals, and computational toxicology modeling. Progress and challenges, including the pressing need to incorporate metabolic activation capability, are summarized.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL CENTER FOR COMPUTATIONAL TOXICOLOGY