Cytotoxicity and genotoxicity of cadmium oxide nanoparticles evaluated using in vitro assays

Eşref Demir; Taichun Qin; Yan Li; Yongbin Zhang; Xiaoqing Guo; Taylor Ingle; Jian Yan; Annamaria Ioana Orza; Alexandru S Biris; Suman Ghorai; Tong Zhou; Tao Chen

doi:10.1016/j.mrgentox.2020.503149

Cytotoxicity and genotoxicity of cadmium oxide nanoparticles evaluated using in vitro assays

Mutat Res Genet Toxicol Environ Mutagen. 2020 Feb-Mar:850-851:503149. doi: 10.1016/j.mrgentox.2020.503149. Epub 2020 Jan 28.

Authors

Eşref Demir¹, Taichun Qin², Yan Li³, Yongbin Zhang⁴, Xiaoqing Guo⁵, Taylor Ingle⁴, Jian Yan⁵, Annamaria Ioana Orza⁶, Alexandru S Biris⁷, Suman Ghorai⁴, Tong Zhou⁸, Tao Chen⁹

Affiliations

¹ Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA; Antalya Bilim University, Faculty of Engineering, Department of Material Science and Nanotechnology Engineering, Antalya, Turkey.
² Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA; Office of Global Regulatory Operations and Policy, U.S. Food and Drug Administration, Los Angeles, CA, USA.
³ Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA; Exploratory Medicine & Pharmacology, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
⁴ Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA.
⁵ Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA.
⁶ Department of Radiology and Imaging Sciences and Center for Systems Imaging, Emory University School of Medicine, Atlanta, GA, USA; CellaCurre LLC., 3630 Peachtree Rd, Atlanta, GA, 30326, USA.
⁷ Center for Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, Little Rock, AR, USA.
⁸ Center for Veterinary Medicine, U.S. Food and Drug Administration, Rockville, MD, USA.
⁹ Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA. Electronic address: Tao.Chen@fda.hhs.gov.

PMID: 32247558
DOI: 10.1016/j.mrgentox.2020.503149

Abstract

Cadmium oxide nanoparticles (CdO NPs) are among some of the most studied and industrially used metal oxide NPs. They have been widely used for industrial application, such as paint pigments and electronic devices, and medical therapeutics. With increasing use of CdO NPs and concerns for their potential adverse effects on the environment and public health, evaluation of the cytotoxicity and genotoxicity of CdO NPs becomes very important. To date, there is a limited understanding of the potential hazard brought by CdO NPs and a lack of information and research, particularly on the genotoxicity assessment of these NPs. In this study, 10 nm CdO core-PEG stabilized NPs were synthesized, characterized and used for evaluation of CdO NPs' cytotoxicity and genotoxicity. Release of cadmium ions (Cd⁺²) from the CdO NPs in cell culture medium, cellular uptake of the NPs, and the endotoxin content of the particles were measured prior to the toxicity assays. Cytotoxicity was evaluated using the MTS assay, ATP content detection assay, and LDH assay. Genotoxicity was assessed using the Ames test, Comet assay, micronucleus assay, and mouse lymphoma assay. The cytotoxicity of cadmium chloride (CdCl₂) was also evaluated along with that of the CdO NPs. The results showed that endotoxin levels within the CdO NPs were below the limit of detection. CdO NPs induced concentration-dependent cytotoxicity in TK6 and HepG2 cells with the MTS, ATP and LDH assays. Although the genotoxicity of CdO NPs was negative in the Ames test, positive results were obtained with the micronucleus, Comet, and mouse lymphoma assays. The negative response of CdO NPs with the Ames test may be the result of unsuitability of the assay for measuring NPs, while the positive responses from other genotoxicity assays suggest that CdO NPs can induce chromosomal damage, single or double strand breaks in DNA, and mutations. The toxicity of the CdO NPs results from the NPs themselves and not from the released Cd⁺², because the ions released from the NPs were minimal. These results demonstrate that CdO NPs are cytotoxic and genotoxic and provide new insights into risk assessment of CdO NPs for human exposure and environmental protection.

Keywords: Cadmium ion; Cadmium oxide nanoparticles; Cell uptake; Cytotoxicity; DNA damage; Endotoxin; Genotoxicity; Mutant frequency.

Published by Elsevier B.V.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Cadmium Compounds / pharmacology
Cadmium Compounds / toxicity*
Cell Line
Cell Survival / drug effects
Comet Assay
DNA Damage / drug effects
Humans
Metal Nanoparticles / chemistry
Metal Nanoparticles / toxicity*
Mice
Mutagenicity Tests*
Mutagens / pharmacology
Mutagens / toxicity*
Oxides / pharmacology
Oxides / toxicity*

Substances

Cadmium Compounds
Mutagens
Oxides
cadmium oxide