Mutations have a profound effect on human health, particularly through an increased risk of carcinogenesis and genetic disease. The strong correlation between mutagenesis and carcinogenesis has been a driving force behind genotoxicity research for more than 50 years. The stochastic and infrequent nature of mutagenesis makes it challenging to observe and to study. Indeed, decades have been spent developing increasingly sophisticated assays and methods to study these low-frequency genetic errors, in hopes of better predicting which chemicals may be carcinogens, understanding their mode of action, and informing guidelines to prevent undue human exposure. While effective, widely used genetic selection-based technologies have a number of limitations that have hampered major advancements in the field of genotoxicity. Emerging new tools, in the form of enhanced next-generation sequencing platforms and methods, are changing this paradigm. In this review, we discuss rapidly evolving sequencing tools and technologies, such as error-corrected sequencing and single cell analysis, which we anticipate will fundamentally reshape the field. In addition, we consider a variety emerging applications for these new technologies, including the detection of DNA adducts, inference of mutational processes based on genomic site and local sequence contexts, and evaluation of genome engineering fidelity, as well as other cutting-edge challenges for the next 50 years of environmental and molecular mutagenesis research. Environ. Mol. Mutagen. 61:135-151, 2020. © 2019 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

中文翻译：

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下一代基因毒理学：使用现代测序技术评估体细胞诱变和癌症风险。

突变对人类健康具有深远的影响，特别是通过增加致癌和遗传疾病的风险。诱变和致癌作用之间的强相关性一直是遗传毒性研究背后的驱动力，已有50多年的历史了。诱变的随机性和罕见性使其难以观察和研究。实际上，已经花费了数十年的时间来开发越来越复杂的测定方法和方法来研究这些低频遗传错误，以期更好地预测哪些化学物质可能是致癌物，了解其作用方式，并提供指导方针以防止人类过度接触。虽然有效，但广泛使用的基于基因选择的技术具有许多局限性，阻碍了遗传毒性领域的重大进步。新兴工具 以增强的下一代测序平台和方法的形式，正在改变这种范例。在这篇综述中，我们讨论了快速发展的测序工具和技术，例如纠错测序和单细胞分析，我们预计它们将从根本上重塑这一领域。此外，我们考虑了这些新技术的各种新兴应用，包括DNA加合物的检测，基于基因组位点和局部序列背景的突变过程的推论，基因组工程保真度的评估以及其他挑战。未来50年的环境和分子诱变研究。环境。大声笑 诱变剂。61：135-151，2020.©2019 The Authors。Wiley Periodicals，Inc.代表环境诱变学会出版的《环境和分子诱变》。