UCIBIO -Applied Molecular Biosciences Unit, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
Unit of Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden.
Int J Environ Res Public Health. 2019 Nov 26;16(23):4718. doi: 10.3390/ijerph16234718.
The last decade witnessed extraordinary advances in "omics" methods, particularly transcriptomics, proteomics and metabolomics, enabling toxicologists to integrate toxicokinetics and toxicodynamics with mechanistic insights on the mode-of-action of noxious chemicals, single or combined. The toxicology of mixtures is, nonetheless, a most challenging enterprise, especially for environmental toxicologists and ecotoxicologists, who invariably deal with chemical mixtures, many of which contain unknowns. Despite costs and demanding computations, the systems toxicology framework, of which "omics" is a major component, endeavors extracting adverse outcome pathways for complex mixtures. Still, the interplay between the multiple components of gene expression and cell metabolism tends to be overlooked. As an example, the proteome allocates DNA methyltransferases whose altered transcription or loss of function by action of chemicals can have a global impact on gene expression in the cell. On the other hand, chemical insult can produce reactive metabolites and radicals that can intercalate or bind to DNA as well as to enzymes and structural proteins, compromising their activity. These examples illustrate the importance of exploring multiple "omes" and the purpose of "omics" and multi-"omics" for building truly predictive models of hazard and risk. Here we will review the state-of-the-art of toxicogenomics highlighting successes, shortcomings and perspectives for next-generation environmental toxicologists.
过去十年见证了“组学”方法的非凡进展，特别是转录组学、蛋白质组学和代谢组学，使毒理学家能够将毒代动力学和毒效动力学与关于有毒化学物质单一或组合作用模式的机制见解相结合。然而，混合物的毒理学是一项极具挑战性的工作，特别是对于环境毒理学家和生态毒理学家来说，他们经常处理化学混合物，其中许多混合物都含有未知物。尽管成本高昂且计算要求苛刻，但以“组学”为主要组成部分的系统毒理学框架努力为复杂混合物提取不良结果途径。尽管如此，基因表达和细胞代谢的多个成分之间的相互作用往往被忽视。例如，蛋白质组分配 DNA 甲基转移酶，其转录的改变或化学物质作用下功能丧失会对细胞中的基因表达产生全局影响。另一方面，化学损伤会产生反应性代谢物和自由基，这些代谢物和自由基可以插入或与 DNA 以及酶和结构蛋白结合，从而损害其活性。这些例子说明了探索多个“组学”以及“组学”和多“组学”对于构建危险和风险真正预测模型的重要性。在这里，我们将回顾毒理基因组学的最新进展，突出其成功、缺点和下一代环境毒理学家的展望。
