Mechanisms and Assessment of Genotoxicity of Metallic Engineered Nanomaterials in the Human Environment

被引:8
作者
Liu, Benjamin M. [1 ,2 ,3 ,4 ,5 ,6 ]
Hayes, A. Wallace [7 ,8 ]
机构
[1] Childrens Natl Hosp, Div Pathol & Lab Med, Washington, DC 20010 USA
[2] George Washington Univ, Sch Med & Hlth Sci, Dept Pediat, Washington, DC 20010 USA
[3] George Washington Univ, Sch Med & Hlth Sci, Dept Pathol, Washington, DC 20037 USA
[4] George Washington Univ, Sch Med & Hlth Sci, Dept Microbiol Immunol & Trop Med, Washington, DC 20037 USA
[5] Childrens Natl Res Inst, Washington, DC 20012 USA
[6] Dist Columbia Ctr AIDS Res, Washington, DC 20052 USA
[7] Univ S Florida, Coll Publ Hlth, Ctr Environm Occupat Risk Anal & Management, Tampa, FL 33612 USA
[8] Michigan State Univ, Inst Integrated Toxicol, E Lansing, MI 48824 USA
关键词
engineered nanomaterials; metallic; genotoxicity; mechanisms; assessment; guidance; DNA damage; CHRONIC HEPATITIS-B; ANTIVIRAL RESISTANCE MUTATIONS; REVERSE-TRANSCRIPTASE; TREATED PATIENTS; TRIM56; SEQUENCES; VIRUSES; IMMUNE; NAIVE;
D O I
10.3390/biomedicines12102401
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 TiO2 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 hprt 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.
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页数:16
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