GENETOXICITY STUDIES OF CHEMOPREDVENTIVE AGENTS - TASK A

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The National Cancer Institute, Division of Cancer Prevention, Chemopreventive Agent Development Research Group directs an investigational chemopreventive agent development program to identify and develop drugs that will prevent, delay, or reverse the process of carcinogenesis. In order to assess safety of investigational new agents, they must be evaluated for their toxicological potential. Toxicity screening includes genetoxicity studies consisting of in vitro and in vivo tests to detect compounds that directly or indirectly induce genetic damage. The currently accepted battery of genetic toxicity tests, as specified by FDA, consists of assays for gene mutation in bacteria, chromosomal damage in mammalian cells, and in vivo chromosomal damage evaluated using rodent bone marrow hematopoetic cells. These requirements can be satisfied by Salmonella histidine reversion mutagenesis (Ames) assay with inclusion of an Escherichia coli tryptophan reversion assay, in vitro chromosomal aberration in Chinese hamster ovary (CHO) cells, and the mouse bone marrow micronucleus assay. Compound selection for the study will be made from the Rapid Access to Preventive Intervention Development (RAPID) Program. The studies shall fulfill current industry standards for toxicology studies supporting NDA application and shall be conducted under FDA Good Laboratory Practice (GLP) regulations in AAALAC accredited, NIH/OPRR & USDA registered laboratories with active Institutional Animal Care and Use Committee (IACUC).