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

Yvonne Kohl,Eleonora Marta Longhin,Elise Rundén-Pran,Michelle Hesler,Maria Dusinska,Espen Mariussen,Naouale El Yamani

doi:10.3390/nano10101911

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.

Highlights

Nanomaterials (NMs) are materials with unique properties and size with at least one dimension between 1 and 100 nm, as defined by the European Commission (Regulation (EC) No 1907/2006) [1]
The development of advanced in vitro models for nanotoxicity assessment is greatly encouraged by the principles of 3Rs, which are embedded in international legislation and regulations on the use of animals for scientific purposes [43]
Besides the general mechanisms of genotoxicity and their verification processes, we have described the additional studies which are needed for a correct implementation of genotoxicity studies

Summary

Introduction

Nanomaterials (NMs) are materials with unique properties and size with at least one dimension between 1 and 100 nm, as defined by the European Commission (Regulation (EC) No 1907/2006) [1]. They have already been in use for several decades, and are being utilized in almost every industrial sector. A main concern with NM exposure is their genotoxic potential. Genotoxicity describes the property of chemical or physical agents that are able to alter the genetic information. Genotoxic events can be transient (repairable damage), or can lead to permanent changes (mutations) in the amount or structure of the genetic material in a cell.

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Conclusion