Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge (INSA), Lisbon, Portugal.
Center for Toxicogenomics and Human Health (ToxOmics), NOVA Medical School-FCM, UNL, Lisbon, Portugal.
Adv Exp Med Biol. 2022;1357:179-194. doi: 10.1007/978-3-030-88071-2_8.
In the last years, "omics" approaches have been applied to study the toxicity of nanomaterials (NM) with the aim of obtaining insightful information on their biological effects. One of the most developed "omics" field, transcriptomics, expects to find unique profiles of differentially-expressed genes after exposure to NM that, besides providing evidence of their mechanistic mode of action, may also be used as biomarkers for biomonitoring purposes. Moreover, several NM have been associated with epigenetic alterations, i.e., changes in the regulation of gene expression caused by differential DNA methylation, histone tail modification and microRNA expression. Epigenomics research focusing on DNA methylation is increasingly common and the role of microRNAs is being better understood, either promoting or suppressing biological pathways. Moreover, the proteome is a highly dynamic system that changes constantly in response to a stimulus. Therefore, proteomics can identify changes in protein abundance and/or variability that lead to a better understanding of the underlying mechanisms of action of NM while discovering biomarkers. As to genomics, it is still not well developed in nanotoxicology. Nevertheless, the individual susceptibility to NM mediated by constitutive or acquired genomic variants represents an important component in understanding the variations in the biological response to NM exposure and, consequently, a key factor to evaluate possible adverse effects in exposed individuals. By elucidating the molecular changes that are involved NM toxicity, the new "omics" studies are expected to contribute to exclude or reduce the handling of hazardous NM in the workplace and support the implementation of regulation to protect human health.
在过去的几年中,“组学”方法已被应用于研究纳米材料 (NM) 的毒性,旨在获得有关其生物效应的深入信息。“组学”领域中最发达的领域之一是转录组学,它期望在暴露于 NM 后找到差异表达基因的独特图谱,这些基因图谱除了提供其作用机制模式的证据外,还可能被用作生物监测目的的生物标志物。此外,一些 NM 与表观遗传改变有关,即由于 DNA 甲基化、组蛋白尾部修饰和 microRNA 表达的差异而导致的基因表达调控变化。越来越多的研究集中在 DNA 甲基化的表观基因组学上,并且对 microRNA 的作用的理解也在不断加深,microRNA 可以促进或抑制生物途径。此外,蛋白质组是一个高度动态的系统,会根据刺激不断变化。因此,蛋白质组学可以识别导致更好地理解 NM 作用机制的蛋白质丰度和/或可变性的变化,同时发现生物标志物。至于基因组学,它在纳米毒理学中还没有得到很好的发展。然而,由组成型或获得性基因组变体介导的 NM 个体易感性是理解 NM 暴露后生物反应变化的重要组成部分,因此也是评估暴露个体中可能的不良影响的关键因素。通过阐明涉及 NM 毒性的分子变化,新的“组学”研究有望有助于排除或减少在工作场所处理危险 NM,并支持实施法规以保护人类健康。