Workshop on “Genetic Toxicology: Opportunities to Integrate New Approaches”

  • Start Date/Time :
  • End Date/Time :
  • Location : Washington, DC (Silver Spring), USA

Workshop Abstract

The discipline of applied genetic toxicology relies primarily on in vitro and in vivo technologies, some of which have been in use for more than 30 years. Though technological advances have led to high-throughput analyses (e.g. Ames II, flow cytometric analyses of micronuclei), development of in vivo assays applicable to all tissues that could be used as follow-up assays (i.e., Comet assay, gene mutations in transgenic animals), pathway analyses (genomic evaluations), and in silico approaches (QSAR), the regulatory testing battery remains unchanged: 1) an in vitro test for gene mutation in bacteria, 2) an in vitro cytogenetic or micronucleus assay with mammalian cells or an in vitro mouse lymphoma thymidine kinase (tk) assay, and in some cases, 3) an in vivo test for chromosomal damage using rodent hematopoietic cells. Though genetic damage is frequently assessed as a key event(s) in the progression of cancer, toxicologists recognize that a wide spectrum of human health effects may be caused by genetic damage.

Our understanding of molecular biology has increased exponentially in recent years, particularly in areas such as epigenetics, miRNA, and genetic structure. Technologies and tools are also being developed in fields outside of genetic toxicology such as 3D tissue cultures, organ cultures, stem cells, and imaging. The purpose of this workshop is to consider the impact that our improved understanding of biology and new technologies might have on our ability to perform genetic toxicology studies to yield information that is more relevant to human hazard and risk assessment for genetic damage. By bringing together expertise from both within and outside the discipline of genetic toxicology, it is hoped that productive discussions can be held to define ways of bridging genetic toxicology to other disciplines, and to identify potential synergies that would result in new approaches to inform more accurate genotoxicity risk assessment.

Workshop Materials

Workshop Program

Workshop Participants

Speaker Bios and Abstracts

Workshop Presentations

Tuesday, April 24, 2012

Overview of ILSI Health and Environmental Sciences Institute
Dr. James Kim, HESI

Genetic Toxicology: Why thinking outside the box?  Overview, rationale and objectives of the workshop
Dr. Véronique Thybaud, Sanofi

Session 1

Alternative experimental models to improve genetic toxicity testing
Dr. Marilyn Aardema,  BioReliance

Overview of the use of 3-dimensional tissue constructs for genotoxicity testing
Dr. Stefan Pfuhler, Procter & Gamble

Development of in vitro toxicity tests using hepatocytes differentiated from human stem cells
Dr. Seiichi Ishida, National Institutes of Health Science, Japan

Humanized models in toxicology and their applications to hazard characterization and risk assessment
Darrell Boverhof, The Dow Chemical Co.

Session 2

Biomarkers of epigenetic changes and their applicability to genetic toxicology
Dr. Bhaskar Gollapudi, The Dow Chemical Co.

A new paradigm for epigenetic control of cell phenotype: Dynamic reprogramming of tRNA modifications and ribosomes controls selective translation of stress response proteins
Dr. Peter Dedon, Massachusetts Institute of Technology

Epigenomics and impact for drug safety sciences
Dr. Jennifer Marlowe, Novartis

Epigenetic traits as biomarkers of carcinogenesis
Dr. Igor Pogribny, U.S. Food and Drug Administration, NCTR

MIR-34 prevents in vivo lung tumor initiation and progression in the therapeutically resistant KRAS;TRP53 mouse model
Dr. Andrea Kasinski, Yale University

Wednesday, April 25, 2012

Workshop: recap of previous day
Dr. James Kim, HESI

Session 3 

New technologies and approaches
Ms. Kristine Witt, National Institute of Environmental Health Sciences

Imaging as an approach to safety assessment
Dr. Bill Slikker, U.S. Food and Drug Administration, NCTR

The Tox21 strategy for detecting genotoxicants
Dr. Ray Tice, National Institute of Environmental Health Sciences

The behavior of genomic signatures of genotoxicity: Effect of dose level and exposure duration
Dr. Scott Auerbach, National Institute of Environmental Health Sciences

Wrap-up: Discussion and next steps
Dr. Bhaskar Gollapudi, The Dow Chemical Co.

Summary Slides

SWOT Analysis

Conclusions and take home messages

Session Outcomes

Contact Us

Health and Environmental Sciences Institute (HESI)
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