Environmental Health Science Research Bureau, Health Canada, Ottawa, Ontario, Canada.
Environ Mol Mutagen. 2020 Jan;61(1):42-54. doi: 10.1002/em.22327. Epub 2019 Oct 10.
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.
五十年前,环境诱变学会(现环境诱变与基因组学学会)成立,其研究重点是生殖细胞诱变以及保护“我们最宝贵的资产”-精子和卵子基因组。然而,五十年过去了,尽管已经有许多研究证明,暴露于实验室啮齿动物的生殖细胞诱变剂会导致后代遗传改变,但对于人类生殖细胞诱变剂是否存在,尚无共识。我们认为,现在是重新评估现有数据的时候了,并得出结论,我们已经有证据表明,存在影响人类生殖细胞的环境暴露。目前缺少的是明确的数据来证明暴露于环境诱变剂的父母的后代中,新出现的突变数量显著增加。我们相信,经过二十多年来在基因组学方面的研究进展,我们已经掌握了生成数据的技术,这些数据将最终证明环境暴露会导致人类后代中可遗传的新出现的变化。我们呼吁研究界利用我们的技术,协同努力,回归我们创始人最初的重点。未来的 50 年必须涉及临床医生、流行病学家、遗传毒理学家、基因组学专家和生物信息学家之间的合作,以精确定义环境暴露如何影响生殖细胞基因组。现在是研究和监管界准备解释即将涌现的数据,并制定框架来管理、沟通和减轻人类生殖细胞诱变剂暴露风险的时候了。环境分子突变学 61:42-54, 2020. © 2019 加拿大女王陛下的权利。