A Return to the Origin of the EMGS: Rejuvenating the Quest for Human Germ Cell Mutagens and Determining the Risk to Future Generations
- Language of the publication
- English
- Date
- 2019-08-31
- Type
- Article
- Author(s)
- Marchetti, Francesco
- Douglas, George R.
- Yauk, Carole L.
- Publisher
- Wiley
Abstract
Fifty years ago, the Environmental Mutagen Society (now Environmental Mutagenesis and Genomics Society) was founded with a laser-focus on germ cell mutagenesis and the protection of “our most vital assets”—the sperm and egg genomes. Yet, five decades on, despite the fact that many agents have been demonstrated to induce inherited changes in the offspring of exposed laboratory rodents, there is no consensus on whether human germ cell mutagens exist. We argue that it is time to reevaluate the available data and conclude that we already have evidence for the existence of environmental exposures that impact human germ cells. What is missing are definite data to demonstrate a significant increase in de novo mutations in the offspring of exposed parents. We believe that with over two decades of research advancing knowledge and technologies in genomics, we are at the cusp of generating data to conclusively show that environmental exposures cause heritable de novo changes in the human offspring. We call on the research community to harness our technologies, synergize our efforts, and return to our Founders' original focus. The next 50 years must involve collaborative work between clinicians, epidemiologists, genetic toxicologists, genomics experts and bioinformaticians to precisely define how environmental exposures impact germ cell genomes. It is time for the research and regulatory communities to prepare to interpret the coming outpouring of data and develop a framework for managing, communicating and mitigating the risk of exposure to human germ cell mutagens. Environ. Mol. Mutagen. 61:42–54, 2020. © 2019 Her Majesty the Queen in Right of Canada
Plain language summary
Health Canada contributes to the development and update of Test Guidelines for the Organisation for the Economic Co-Operation and Development (OECD). These guidelines are internationally accepted and used for evaluating the safety of chemicals before they come on the market. One of these OECD test guidelines (TG 488) uses genetically modified rodent (eg, mouse and rat) models, called transgenic rodents (TGR), that allow the detection of mutations (changes in the DNA sequence) in any tissue in the body. Health Canada is leading the update of TG 488 regarding the experimental designs for detecting mutations in germ cells (the sperm and egg) and is recognized as an international leader in this area. On occasion of the 50th anniversary of the founding of the Environmental Mutagenesis and Genomics Society, the premier international scientific society that focuses on the role of environmental chemicals on the induction of mutations, Health Canada scientists have been invited to contribute a manuscript on germ cell mutagenesis. The present publication summarizes the advances in germ cell mutagenesis over the past six decades, the role played by TGR models in understanding the mechanisms by which chemicals cause mutations, and discusses the impact that new genomics technologies that allow the identification of mutations over the entire genome will have on the way chemicals are assessed for their ability to damage the germ cell genome. This will require the research and regulatory communities to work together to develop a framework for managing, communicating and mitigating the risk of exposure to environmental germ cell mutagens.
Subject
- Health,
- Health and safety