Genotoxicity of Nanomaterials: Advanced In Vitro Models and High Throughput Methods for Human Hazard Assessment—A Review

Abstract

Changes in the genetic material can lead to serious human health defects, as mutations in somatic cells may cause cancer and can contribute to other chronic diseases. Genotoxic events can appear at both the DNA, chromosomal or (during mitosis) whole genome level. The study of mechanisms leading to genotoxicity is crucially important, as well as the detection of potentially genotoxic compounds. We consider the current state of the art and describe here the main endpoints applied in standard human in vitro models as well as new advanced 3D models that are closer to the in vivo situation. We performed a literature review of in vitro studies published from 2000–2020 (August) dedicated to the genotoxicity of nanomaterials (NMs) in new models. Methods suitable for detection of genotoxicity of NMs will be presented with a focus on advances in miniaturization, organ-on-a-chip and high throughput methods.

Functionalized Silica Star-Shaped Nanoparticles and Human Mesenchymal Stem Cells: An In Vitro Model

“…Moreover, all NPs were biocompatible for stem cells, as demonstrated by the absence of metabolic alteration (similar expression of SOD1, an enzyme that is involved in the maintenance of cell physiology due to its detoxifying activity [ 66 , 67 , 79 ]; similarly, vital Acridine Orange staining, an assay that allows monitoring the presence of storage material within the cells, and the autophagic process [ 69 ]). Of note, we observed that 10–17% of hBM-MSCs and hASCs cultured on s-MSN-Au expressed the histone pH2AX, which is a quantitative marker of DNA double-strand breaks caused by different types of physical agents (e.g., ionizing radiation, radiomimetic drugs), chemical agents, and a wide range of genotoxins [ 80 , 81 ]. This result agreed in part with other studies showing the potential cytotoxic effect of gold-shaped NPs [ 82 ] but diverged for the low grade of toxicity that we observed in both stem cell types and mostly for the absence of cell proliferation arrest.…”

Biocompatibility assessment of biomaterials used in orthopedic devices: An overview (Review)

“…Genotoxicity evaluation is an essential part of the safety assessment of biomaterials as damage of genetic material may result in the induction of carcinogenesis or may alter the reproductive function if germ cell DNA is impaired. The sensitive genotoxicity endpoints comprise DNA damage, gene mutations and chromosomal damage ( 30 , 31 ). The genotoxic risk assessment of biomaterials is performed in mammalian and non-mammalian systems ( 3 ).…”

Suitability of the In Vitro Cytokinesis-Block Micronucleus Test for Genotoxicity Assessment of TiO2 Nanoparticles on SH-SY5Y Cells

“…Therefore, results observed in these experiments indicate that the two treatment options recommended for testing nanomaterials by the CBMN assay are not good options in this particular case, since they resulted similar than the standard cotreatment, and the data obtained substantially differed from those coming from FCMN test in the absence of Cyt-B. Following the recommendations provided by OECD WPMN [22], a number of researchers evaluated MN induction by TiO 2 NP exposure applying either post-treatment [12,[70][71][72] or delayed co-treatment [51,55,73,74] in a number of different cell types. Similar to our results, these studies frequently found increases in MN frequency after TiO 2 NP exposure.…”