Genetic and Reproductive Toxicology

Director: Martha Moore, Ph.D.

The Division of Genetic and Reproductive Toxicology (DGRT) conducts basic and applied research to address specific high-priority issues related to the induction of genetic damage. Division research is directed toward developing and validating new methods or improving existing methods for the identification of potentially hazardous food additives, human and animal drugs, biological therapies, and medical devices. In collaboration with other FDA scientists, DGRT utilizes the methodologies it develops to understand the potential toxicity of specific high-priority drugs, dietary supplements, and other agents. 

As experts in the field of genetic toxicology, scientists in DGRT are actively involved in national and international efforts to harmonize the conduct of genetic-toxicology tests and to improve their interpretation and use for regulatory decision making. DGRT scientists frequently provide expert advice to the FDA Centers, other government agencies, academia, and industry. They also are active participants in the FDA Genetic Toxicology Network, the CDER Genetic Toxicology Network, and other interagency workgroups. 

The Division’s research is divided into the three research areas listed below and is being used to improve the ability of FDA to incorporate new and powerful technologies into regulatory decision making. 

1. genetic-toxicology research addresses the development of methods to assess the potential for chemicals to negatively impact human-genetic material or the function of the genetic material
2. dietary research primarily focuses on the potential hazards of dietary supplements
3. omics research, coupled with more traditional approaches 

DGRT activities provide both direct support for, and the generation of, new approaches used by FDA Centers and, in particular, provide research and expertise directly related to the FDA Critical Path Initiative.

Ongoing Research Projects

• ACB-PCR Measurement of Azoxymethane-Induced Rat K-ras codon 12 GGT-->GAT and GTT-->GTT Mutations in Colonic Aberrant Crypt Foci Isolated using Laser Capture Microdissection (E0714901)
• Analysis of p53 Codon 270 CGT to TGT Mutation in Simulated Solar Light-Induced Skin Tumors and Exposed Mouse Skin (E0715201)
• Cancer Mutations as Biomarkers of Cancer Risk: Human Studies with Implications for Personalized Medicine (E0726501)
• Comparison of Mutation Induction and Types of Mutations in the cII Gene of Big Blue Mice Treated with Carcinogens as Neonates and Adults (E0709001)
• Development of a New Safety Evaluation Method Using MicroRNA (miRNA) Expression Analysis as a Biomarker for Detecting Carcinogens (E0728101)
• Development of a New T-cell Receptor (TCR) Gene Rat Model for Safety Screening of Pharmaceuticals and Other Chemicals for Potential Mutagenicity (E0719601)
• Development of High Throughput Methodology for Detection of In Vivo Mutation in the Endogenous PIG-A Gene of Human Blood Cells Using Flow Cytometry (E0728301)
• Development of Methods for Evaluating DNA Damage using Single Cell Gel Electrophoresis (Comet Assay) in Rodents (E0729001)
• DNA Adduct Formation, Mutations and Patterns of Gene Expression in Big Blue Rats Treated with the Botanical Carcinogens Riddelliine, Aristolochic Acid (AA), and Comfrey (E0710001)
• Effect of p53 Genotype on Gene Expression Profiles in Mice Exposed to the Model Mutagen, N-ethyl-N'-nitrosourea (ENU) (E0712901)
• Evaluating the Utility of ACB-PCR in Dose-Response Assessment and Mode-of-Action Evaluation (E0726901)
• Evaluation of Growth and Pubertal Development in Male Rhesus Monkeys (Macaca mulatta) Chronically Exposed to Methylphenidate Hydrochloride (MPH) (E0728701)
• Evaluation of the Ability of Both the Agar and Microwell Versions of the Mouse Lymphoma Assay (MLA) to Optimally Detect the Mutagenic Potential and Potency of Complex Chemical Mixtures (E0728401)
• Evaluation of the Genetic Toxicity and Behavioral Effects of Chronic Methylphenidate Exposure in Juvenile Male Rhesus Monkeys (Macaca mulatta) (E0723401)
• Evaluation of the Genotoxicity and Pharmacokinetics of Methylphenidate in Male Big Blue Mice (E0723501)
• Further Evaluation of the Types of Genetic Events Detected by the Mouse Lymphoma Assay (MLA) and the Role of the Assay in Mechanistically Based Risk Assessment (E0711701)
• Measurement of Cancer-Associated Gene Mutation in Colon Tumor and Non-Tumor Tissue (E0716001)
• Methods Development for Measurement of Bone Density and Bone Growth in the Rhesus Monkey (Macaca mulatta) (P00700)
• Methods Development for Measurement of Cardiovascular Parameters in the Rhesus Monkey (Macaca mulatta) (P00701)
• Phosphatidylinositol Glycan - Complementation Group A (PIG-A) Mutagenesis: Development of Methods for the Identification and Molecular Characterization of Mutations in the PIG-A Gene in Human Lymphoblastoid Cells and C57Bl/6 Mice (E0720901)

NCTR's Annual Report contains information on the latest accomplishments and plans for the Division of Genetic and Reproductive Toxicology as well as project and publication listings.