Biomedical Engineering Reference
In-Depth Information
17
Genotoxicity of Nanoparticles
Amaya Azqueta, Leire Arbillaga, and Adela López de Cerain
CONTENTS
17.1 Genotoxicity Testing of Nanoparticles: Nanogenotoxicology .............................................. 353
17.2 Mechanism of Action............................................................................................................ 355
17.3
In Vitro
versus
In Vivo
Assays, What Do They Tell Us? ...................................................... 355
17.4 State of the Art: Study of Methods Used in Nanogenotoxicology ....................................... 355
17.5 Tests Used in Nanogenotoxicology ....................................................................................... 356
17.5.1 Comet Assay ............................................................................................................. 357
17.5.2 Micronucleus Test ..................................................................................................... 357
17.5.3 Bacterial Reverse Mutation Test: Ames Test ............................................................ 358
17.5.4 Previous
In Vitro
Cytotoxicity Studies ..................................................................... 358
17.6 Test Conditions That Influence the Genotoxicity of NPs ..................................................... 358
17.7 Characteristics of NPs That Influence Potential Genotoxicity ............................................. 359
17.8 Conclusion ............................................................................................................................ 360
References ..................................................................................................................................... 360
17.1 GENOTOXICITY TESTING OF NANOPARTICLES:
NANOGENOTOXICOLOGY
In the last two decades, the production and use of nanoparticles (NPs) have impressively increased.
NPs have been defined as particles in a nanometer scale with at least one dimension of 100 nm or
less, although, in the case of pharmaceutical NPs, the dimension should be in the nanometer range
(Bawa et al. 2005).
NPs possess different physical, chemical, and biological properties compared with bulk materi-
als of the same composition. The small size, keeping the mass unchanged with respect to the same
bulk material, entails an increase in the surface area and, consequently, in the number of atoms that
can react to produce a certain activity. Owing to their special characteristics, NPs are applied in
several areas, including biomedicine. There are enormous potential advantages of nanotechnology
in medicine and its wide use has given rise to a new area of medicine and research called nanomedi-
cine. NPs are used in preventing diseases, as well as diagnosing, monitoring, treating (e.g., drug
carriers), and relieving pain.
Nevertheless, the small size and the large surface area improve the cellular uptake, but may lead
to cellular accumulations with poor clearances and subsequent chronic toxicities (Landsiedel et al.
2009; Singh et al. 2009). Biological nanomaterials are normally biodegradable and biocompatible
and are considered to be less toxic or nontoxic to the human body (Kim et al. 2010b). In contrast,
insoluble nanomaterials may accumulate in human tissues and organs and exert toxic effects over
long-term administrations. Nanotoxicology is a special branch of toxicology that studies the adverse
effects of NPs on living systems. The main problem of this new area is the fact that the term NP is
too broad, as it covers particles with very different physical, chemical, and biological properties.
Genotoxicity studies are crucial for assessing the safety of NPs for the development of pos-
sible medical applications. The cell nucleus is one of the desired targets, implying a possible
interaction with DNA and a possible induction of genetic damage. NPs can also reach the nucleus
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