Liu Benjamin M, Hayes A Wallace
Division of Pathology and Laboratory Medicine, Children's National Hospital, Washington, DC 20010, USA.
Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC 20010, USA.
Biomedicines. 2024 Oct 20;12(10):2401. doi: 10.3390/biomedicines12102401.
Engineered nanomaterials (ENMs) have a broad array of applications in agriculture, engineering, manufacturing, and medicine. Decades of toxicology research have demonstrated that ENMs can cause genotoxic effects on bacteria, mammalian cells, and animals. Some metallic ENMs (MENMs), e.g., metal or metal oxide nanoparticles TiO and CuO, induce genotoxicity via direct DNA damage and/or reactive oxygen species-mediated indirect DNA damage. There are various physical features of MENMs that may play an important role in promoting their genotoxicity, for example, size and chemical composition. For a valid genotoxicity assessment of MENMs, general considerations should be given to various factors, including, but not limited to, NM characterization, sample preparation, dosing selection, NM cellular uptake, and metabolic activation. The recommended in vitro genotoxicity assays of MENMs include gene mutation assay, chromosomal aberration assay, and micronucleus assay. However, there are still knowledge gaps in understanding the mechanisms underlying the genotoxicity of MENMs. There are also a variety of challenges in the utilization and interpretation of the genotoxicity assessment assays of MENMs. In this review article, we provide mechanistic insights into the genotoxicity of MENMs in the human environment. We review advances in applying new endpoints, biomarkers, and methods to the genotoxicity assessments of MENMs. The guidance of the United States, the United Kingdom, and the European Union on the genotoxicity assessments of MENMs is also discussed.
工程纳米材料（ENMs）在农业、工程、制造业和医学等领域有着广泛的应用。数十年的毒理学研究表明，ENMs可对细菌、哺乳动物细胞和动物产生遗传毒性作用。一些金属工程纳米材料（MENMs），例如金属或金属氧化物纳米颗粒TiO和CuO，通过直接DNA损伤和/或活性氧介导的间接DNA损伤诱导遗传毒性。MENMs的各种物理特性可能在促进其遗传毒性方面发挥重要作用，例如尺寸和化学成分。为了对MENMs进行有效的遗传毒性评估，应综合考虑各种因素，包括但不限于纳米材料表征、样品制备、剂量选择、纳米材料细胞摄取和代谢活化。推荐的MENMs体外遗传毒性试验包括基因突变试验、染色体畸变试验和微核试验。然而，在理解MENMs遗传毒性的潜在机制方面仍存在知识空白。在MENMs遗传毒性评估试验的应用和解释方面也存在各种挑战。在这篇综述文章中，我们提供了关于人类环境中MENMs遗传毒性的机制见解。我们回顾了在将新的终点、生物标志物和方法应用于MENMs遗传毒性评估方面取得的进展。还讨论了美国、英国和欧盟关于MENMs遗传毒性评估的指南。
