Genetic Toxicology Group
Kristine L. Witt, M.S.
Health Science Evaluator, Group Leader
The Genetic Toxicology Group, headed by Kristine Witt, M.S., is responsible for testing chemicals of interest to the National Toxicology Program (NTP) for ability to induce measurable changes in DNA and chromosomes that may result in human diseases (e.g., cancer) or increase the risk of birth defects, as part of the overall toxicological assessment of a chemical.
Exposure conditions that are investigated may be acute, subacute, or long term. A variety of test systems are employed, including bacteria, cultured mammalian and human cells, and laboratory rodents. Collaborations with the NIEHS Clinical Research Unit provide an opportunity for translational studies to assess genetic effects in human populations.
Current testing capabilities:
- Bacterial mutagenicity testing (Ames assay)
- in vitro and in vivo Micronucleus (MN) testing
- in vitro and in vivo Comet assay
- Combined in vivo MN/Comet assay
- Pig-a mutation assay in vivo in rat and mouse erythrocytes
Current research projects:
- Black Cohosh Clinical Study – We are investigating the genotoxic, hematological, and metabolomic effects of black cohosh herbal products in women. This study is designed to determine if the effects seen in NTP animal studies are also observed in humans ( Mercado-Feliciano et al., 2012; Toxicol. Appl. Pharmacol. 263:138-147).
- Evaluation of comparative genotoxicity among several cohoshes – An in vitro micronucleus assay in TK6 cells is in progress to evaluate chromosome damaging potential of several different commercially available cohosh samples to understand the relationship between chemical composition of the samples and genotoxic activity.
- Tox21 Genotoxicity Prediction and Prioritization Project – The goals of this project are to evaluate and interpret the results from five quantitative high throughput screens that each measure some aspect of DNA damage/repair, and to determine how these results may be used as replacements or adjuncts to traditional assays for genotoxicity.
- Comprehensive meta-analysis of data on chromosomal damage in hospital personnel occupationally exposed to cytostatic chemotherapeutic agents – This collaboration with NIOSH investigators aims to determine the reliability of the published data on these exposures and whether the data establish a clear health risk to workers from occupational exposure to cytostatic drugs. In the event that elevated levels of chromosomal damage are clearly documented, increased personal protective measures could reduce or eliminate the risk.
- Comprehensive characterization of the genotoxicity of glyphosate formulations – An effort is underway to systematically review the published genotoxicity reports for glyphosate and its formulations to identify possible data gaps and design studies to fill these gaps to clarify contrasting conclusions regarding the potential carcinogenicity of this widely used herbicide.
Kristine Witt, M.S., is a health science evaluator in the Biomolecular Screening Branch of the National Toxicology Program (NTP). Witt manages the NTP’s genetic toxicology testing contract, and provides genetic toxicology test data review and evaluation for inclusion in the NTP Technical Reports. She is also involved in assay selection and study design for the NTP’s High Throughput Screening initiative and serves as co-chair of the Assays and Pathways Working Group for the Tox21 collaboration.
In addition to her work for NTP, Witt manages NIEHS research studies on cytogenetic endpoints in study populations exposed to medications with known or suspected genetic toxicity, with an emphasis on exposure risks to children. She has an extensive background in both clinical cytogenetics and genetic toxicology and has made numerous presentations at national meetings and workshops.
Witt received a B.S. in zoology and an M.S. in genetics from The Ohio State University. She is an active member of the Environmental Mutagenesis and Genomics Society (EMGS), the Genetics and Environmental Mutagenesis Society (GEMS), the Genetic Toxicology Association, and the ILSI/HESI Genetic Toxicology Technical Committee. She has served on EMGS Council (2011 – 2014) and numerous committees and special interest groups; she also chaired the Women in the Environmental Mutagenesis and Genomics Society Group (2009 – 2014) and currently co-chairs the Publication Policy Committee. She has served as a councilor on the GEMS board on three occasions (1991 – 1994, 1998 – 2001, 2007 – 2009). Witt has also served on an IARC Monograph Panel (Number 108) and is a member of the OECD Expert Group on Genetic Toxicology Test Guidelines. She serves on the Editorial Board of Mutation Research, Environmental and Genetic Toxicology section, and regularly reviews submitted manuscripts for genetic and environmental science journals.