title: Emerging metrology for high-throughput nanomaterial genotoxicology.
abstract: The rapid development of the engineered nanomaterial (ENM) manufacturing industry has accelerated the incorporation of ENMs into a wide variety of consumer products across the globe. Unintentionally or not, some of these ENMs may be introduced into the environment or come into contact with humans or other organisms resulting in unexpected biological effects. It is thus prudent to have rapid and robust analytical metrology in place that can be used to critically assess and/or predict the cytotoxicity, as well as the potential genotoxicity of these ENMs. Many of the traditional genotoxicity test methods [e.g. unscheduled DNA synthesis assay, bacterial reverse mutation (Ames) test, etc.,] for determining the DNA damaging potential of chemical and biological compounds are not suitable for the evaluation of ENMs, due to a variety of methodological issues ranging from potential assay interferences to problems centered on low sample throughput. Recently, a number of sensitive, high-throughput genotoxicity assays/platforms (CometChip assay, flow cytometry/micronucleus assay, flow cytometry/γ-H2AX assay, automated 'Fluorimetric Detection of Alkaline DNA Unwinding' (FADU) assay, ToxTracker reporter assay) have been developed, based on substantial modifications and enhancements of traditional genotoxicity assays. These new assays have been used for the rapid measurement of DNA damage (strand breaks), chromosomal damage (micronuclei) and for detecting upregulated DNA damage signalling pathways resulting from ENM exposures. In this critical review, we describe and discuss the fundamental measurement principles and measurement endpoints of these new assays, as well as the modes of operation, analytical metrics and potential interferences, as applicable to ENM exposures. An unbiased discussion of the major technical advantages and limitations of each assay for evaluating and predicting the genotoxic potential of ENMs is also provided.
authors: National Institute of Standards and Technology, Material Measurement Laboratory - Biosystems and Biomaterials Division, 100 Bureau Drive, Gaithersburg, MD 20899, USA, bryant.nelson@nist.gov.
authors: Bryant C
authors: BC
authors: Nelson
authors: Department of Environmental Health, Center for Nanotechnology and Nanotoxicology, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue Building 1/Room 1309, Boston, MA 02115, USA.
authors: Christa W
authors: CW
authors: Wright
authors: Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
authors: Yuko
authors: Y
authors: Ibuki
authors: Department of Biology, University of Konstanz, Molecular Toxicology Group, D-78457 Konstanz, Germany.
authors: Maria
authors: M
authors: Moreno-Villanueva
authors: Unit of Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 17177 Stockholm, Sweden.
authors: Hanna L
authors: HL
authors: Karlsson
authors: Toxys, Robert Boyleweg 4, 2333 CG Leiden, The Netherlands.
authors: Giel
authors: G
authors: Hendriks
authors: National Institute of Standards and Technology, Material Measurement Laboratory - Biosystems and Biomaterials Division, 100 Bureau Drive, Gaithersburg, MD 20899, USA.
authors: Christopher M
authors: CM
authors: Sims
authors: Faculty of Health and Life Sciences, School of Allied Health Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, UK and.
authors: Neenu
authors: N
authors: Singh
authors: Swansea University Medical School, Institute of Life Science, Centre for NanoHealth, Swansea University Medical School, Wales SA2 8PP, UK.
authors: Shareen H
authors: SH
authors: Doak
mesh_terms: D000818:Animals; D001419:Bacteria / Q000187:drug effects / Q000235:genetics; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D009152:Mutagenicity Tests / Q000379:methods*; D049329:Nanostructures / Q000633:toxicity*
chemical_list: D004247:DNA