Critical review of the current and future challenges associated with advanced in vitro systems towards the study of nanoparticle (secondary) genotoxicity.
With the need to understand the potential biological impact of the plethora of nanoparticles (NPs) being manufactured for a wide range of potential human applications, due to their inevitable human exposure, research activities in the field of NP toxicology has grown exponentially over the last decade. Whilst such increased research efforts have elucidated an increasingly significant knowledge base pertaining to the potential human health hazard posed by NPs, understanding regarding the possibility for NPs to elicit genotoxicity is limited. In vivo models are unable to adequately discriminate between the specific modes of action associated with the onset of genotoxicity. Additionally, in line with the recent European directives, there is an inherent need to move away from invasive animal testing strategies. Thus, in vitro systems are an important tool for expanding our mechanistic insight into NP genotoxicity. Yet uncertainty remains concerning their validity and specificity for this purpose due to the unique challenges presented when correlating NP behaviour in vitro and in vivo This review therefore highlights the current state of the art in advanced in vitro systems and their specific advantages and disadvantages from a NP genotoxicity testing perspective. Key indicators will be given related to how these systems might be used or improved to enhance understanding of NP genotoxicity.
In Vitro Toxicology Group, Institute of Life Science and Centre for NanoHealth, Swansea Univeristy Medical School, Swansea University, Singleton Park, Swansea SA2 8PP, Wales, UK.
Stephen J
SJ
Evans
In Vitro Toxicology Group, Institute of Life Science and Centre for NanoHealth, Swansea Univeristy Medical School, Swansea University, Singleton Park, Swansea SA2 8PP, Wales, UK.
Martin J D
MJ
Clift
Faculty of Health Sciences and Life Sciences, School of Allied Health Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, UK.
Neenu
N
Singh
In Vitro Toxicology Group, Institute of Life Science and Centre for NanoHealth, Swansea Univeristy Medical School, Swansea University, Singleton Park, Swansea SA2 8PP, Wales, UK.
Jefferson
J
de Oliveira Mallia
In Vitro Toxicology Group, Institute of Life Science and Centre for NanoHealth, Swansea Univeristy Medical School, Swansea University, Singleton Park, Swansea SA2 8PP, Wales, UK.
Michael
M
Burgum
Environmental Health Sciences and Research Bureau, Health Canada, 50 Colombine Driveway, Ottawa, Ontario K1A 0K9, Canada and.
John W
JW
Wills
Microbiology and Infectious Diseases, Institute of Life Science, MRC CLIMB Centre, Swansea University Medical School, Singleton Park, Swansea SA2 8PP, UK.
Thomas S
TS
Wilkinson
In Vitro Toxicology Group, Institute of Life Science and Centre for NanoHealth, Swansea Univeristy Medical School, Swansea University, Singleton Park, Swansea SA2 8PP, Wales, UK.
Gareth J S
GJ
Jenkins
In Vitro Toxicology Group, Institute of Life Science and Centre for NanoHealth, Swansea Univeristy Medical School, Swansea University, Singleton Park, Swansea SA2 8PP, Wales, UK, s.h.doak@swansea.ac.uk.
Shareen H
SH
Doak
D000818:Animals; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D006801:Humans; D009152:Mutagenicity Tests / Q000379:methods*; D053758:Nanoparticles / Q000633:toxicity*
D004247:DNA