Genotoxicity evaluation of zinc oxide nanoparticles in Swiss mice after oral administration using chromosomal aberration,micronuclei,semen analysis,and RAPD profile
Restricted accessResearch articleFirst published online November, 2017
Genotoxicity evaluation of zinc oxide nanoparticles in Swiss mice after oral administration using chromosomal aberration,micronuclei,semen analysis,and RAPD profile
The expanded uses of zinc oxide nanoparticles (ZnO NPs) have grown rapidly in the field of nanotechnology. Thus, rising production of nanoparticles (NPs) increases the possible risks to the environment and occupationally exposed humans. Hence, it is indispensable to appraise the safety toxicity including genotoxicity for these NPs. In the present study, we have evaluated the genotoxic effect of ZnO NPs after oral administration to Swiss mice at dose levels of 300 and 2000 mg/kg body weight. These doses were administered for 2 days at 24 h apart. Chromosomal aberration (CA) and micronucleus tests were conducted following Organization for Economic Co-operation and Development guidelines. DNA damage was evaluated at 0, 24, 48, and 72 h posttreatment using a randomly amplified polymorphic DNA (RAPD) assay; additionally, semen analyses were also performed at 34.5 days post oral exposure. The reactive oxygen species (ROS), 8-oxo-2′-deoxyguanosine and CAs were increased (p < 0.05) at the highest dosage (2000 mg/kg) of ZnO NPs compared to controls. Aberrant sperm morphology with reduced sperm count and motility were also present (p < 0.05) in the high-dose group. Based on the RAPD assay, the genomic template stability within the high-dose group (<90%) was less than the controls (100%). The results suggested that ZnO NPs are mildly genotoxic in a dose-related manner and this toxicity were induced by generation of ROS.
AdlerID (1984) Cytogenetic tests in mammals. In: VenittSParryJM (eds) Mutagenicity Testing: A Practical Approach. Oxford: IRL Press, pp. 275–306.
2.
AtienzarFAConradiMEvendenAJ. (1999) Qualitative assessment of genotoxicity using random amplified polymorphic DNA: comparison of genomic template stability with key fitness parameters in Daphnia magna exposed to benzo [a] pyrene. Environmental Toxicology and Chemistry18(10): 2275–2282.
3.
AtienzarFAVenierPJhaAN. (2002) Evaluation of the random amplified polymorphic DNA (RAPD) assay for the detection of DNA damage and mutations. Mutation Research/Genetic Toxicology and Environmental Mutagenesis521(1): 151–163.
4.
BarnesCAElsaesserAArkuszJ. (2008) Reproducible comet assay of amorphous silica nanoparticles detects no genotoxicity. Nano Letters8(9): 3069–3074.
5.
BartkeAWeirJAMathisonP. (1974) Testicular function in mouse strains with different age of sexual maturation. Journal of Heredity65(4): 204–208.
6.
BjörndahlL (2010) The usefulness and significance of assessing rapidly progressive spermatozoa. Asian Journal of Andrology12(1): 33.
7.
BlazakWFTreinenKAJuniewiczPE (1993) Application of testicular sperm head counts in the assessment of male reproductive toxicity. In: ChapinRE and HeindelJJ (eds) Methods in Toxicology, Vol. 3, Pt. A. Male Reproductive Toxicology. San Diego, CA: Academic Press, pp. 86–94.
8.
BormPJAKreylingW (2004) Toxicological hazards of inhaled nanoparticles potential implications for drug delivery. Journal of Nanoscience and Nanotechnology4(5): 521–531.
9.
Braydich-StolleLHussainSSchlagerJJ. (2005) In vitro cytotoxicity of nanoparticles in mammalian germline stem cells. Toxicological Sciences88(2): 412–419.
CadetJWagnerJR (2013) DNA base damage by reactive oxygen species, oxidizing agents, and UV radiation. Cold Spring Harbor Perspectives in Biology5(2): a012559.
12.
CarmonaERInostroza-BlancheteauCRubioL. (2016) Genotoxic and oxidative stress potential of nanosized and bulk zinc oxide particles in Drosophila melanogaster. Toxicology and Industrial Health32(12): 1987–2001.
13.
ChandraSChauhanLKSDhawanA. (2006) In vivo genotoxic effects of industrial waste leachates in mice following oral exposure. Environmental and Molecular Mutagenesis47(5): 325–333.
14.
ChenYXueZZhengD. (2003) Sodium chloride modified silica nanoparticles as a non-viral vector with a high efficiency of DNA transfer into cells. Current Gene Therapy3(3): 273–279.
15.
CoetzeeKKrugeTFLombardCJ (1998) Predictive value of normal sperm morphology: a structured literature review. Human Reproduction Update4(1): 73–82.
16.
DufourEKKumaravelTNohynekGJ. (2006) Clastogenicity, photo-clastogenicity or pseudo-photo-clastogenicity: genotoxic effects of zinc oxide in the dark, in pre-irradiated or simultaneously irradiated Chinese hamster ovary cells. Mutation Research/Genetic Toxicology and Environmental Mutagenesis607(2): 215–224.
17.
GhoshMSinhaSJothiramajayamM. (2016) Cyto-genotoxicity and oxidative stress induced by zinc oxide nanoparticle in human lymphocyte cells in vitro and Swiss albino male mice in vivo. Food and Chemical Toxicology97: 286–296.
18.
Gil-GuzmanEOlleroMLopezMC. (2001) Differential production of reactive oxygen species by subsets of human spermatozoa at different stages of maturation. Human Reproduction16(9): 1922–1930.
19.
GriffittRJWeilRHyndmanKA. (2007) Exposure to copper nanoparticles causes gill injury and acute lethality in zebrafish (Danio rerio). Environmental Science & Technology41(23): 8178–8186.
20.
HoodE (2004) Nanotechnology: looking as we leap. Environmental Health Perspectives112(13): A740.
21.
JalaliMSakiGSarkakiAR. (2012) Effect of noise stress on count, progressive and non-progressive sperm motility, body and genital organ weights of adult male rats. Journal of Human Reproductive Sciences5(1): 48.
22.
KangTGuanRChenX. (2013) In vitro toxicity of different-sized ZnO nanoparticles in Caco-2 cells. Nanoscale Research Letters8(1): 496.
23.
KesslerR (2011) Engineered nanoparticles in consumer products: understanding a new ingredient. Environmental Health Perspectives119(3): A120–A125.
24.
KisinERMurrayARKeaneMJ. (2007) Single-walled carbon nanotubes: geno-and cytotoxic effects in lung fibroblast V79 cells. Journal of Toxicology and Environmental Health, Part A70(24): 2071–2079.
25.
KumarMKumarS (2014) Genetic structure and inter-generic relationship of closed colony of laboratory rodents based on RAPD markers. Molecular Biology Reports41(11): 7273–7280.
26.
KútvölgyiGSteflerJKovácsA (2006) Viability and acrosome staining of stallion spermatozoa by Chicago sky blue and Giemsa. Biotechnic & Histochemistry81(4–6): 109–117.
27.
KwonJYLeeSYKoedrithP. (2015) Lack of genotoxic potential of ZnO nanoparticles in in vitro and in vivo tests. Mutation Research/Genetic Toxicology and Environmental Mutagenesis761: 1–9.
28.
LiangX-JChenCZhaoY. (2008) Biopharmaceutics and therapeutic potential of engineered nanomaterials. Current Drug Metabolism9(8): 697–709.
29.
LindholmerCH (1974) The importance of seminal plasma for human sperm motility. Biology of Reproduction10(5): 533–542.
30.
MagdolenovaZCollinsAKumarA. (2013) Mechanisms of genotoxicity. A review of in vitro and in vivo studies with engineered nanoparticles. Nanotoxicology8(3): 233–278.
31.
McWilliamsA (112016) The manufacturing nanotechnology market: products and application. Global Markets. BCC Research ReportsReport ID: NANO31G. Available at: WWW.bcccresearch.com (accessed 1 September 2017).
32.
MemarzadehKShariliASHuangJ. (2015) Nanoparticulate zinc oxide as a coating material for orthopedic and dental implants. Journal of Biomedical Materials Research Part A103(3): 981–989.
33.
MoosPJChungKWoessnerD. (2010) ZnO particulate matter requires cell contact for toxicity in human colon cancer cells. Chemical Research in Toxicology23(4): 733–739.
34.
OECD (2010) No. 27: Environment, Health and Safety Publications Series on the Safety of Manufactured Nanomaterials. Paris.
OECD (2014) Test No. 475: Mammalian Bone Marrow Chromosomal Aberration Test. Paris: OECD Publishing.
37.
PageRD (1996) TREE VIEW: an application to display phylogenetic tree on personal computer. Computer Applications in the Biosciences12: 357–358.
38.
RayaSeDAHassanMIFarrohKY. (2016) Zinc oxide nanoparticles fortified biscuits as a nutritional supplement for zinc deficient rats. Journal of Nanomedicine Research4(2): 1–7.
39.
RoccoLValentinoIVScapigliatiG. (2013) RAPD-PCR analysis for molecular characterization and genotoxic studies of a new marine fish cell line derived from Dicentrarchus labrax. Cytotechnology66(3): 383–393.
40.
SargentJF (2013) Nanotechnology: A Policy Primer, CRS Report for Congress, Library of Congress. Congressional Research Service.
41.
SavvaD (1998) Use of DNA fingerprinting to detect genotoxic effects. Ecotoxicology and Environmental Safety41(1): 103–106.
42.
SchmidW (1975) The micronucleus test. Mutation Research/Environmental Mutagenesis and Related Subjects31(1): 9–15.
43.
SchmidW (1976) The micronucleous test for cytogenetic analysis. Chemical Mutagenesis, Principles and Methods for their Detection4: 31–53.
44.
SharmaVSinghSKAndersonD. (2011) Zinc oxide nanoparticle induced genotoxicity in primary human epidermal keratinocytes. Journal of Nanoscience and Nanotechnology11(5): 3782–3788.
45.
SharmaVSinghPPandeyAK. (2012) Induction of oxidative stress, DNA damage and apoptosis in mouse liver after sub-acute oral exposure to zinc oxide nanoparticles. Mutation Research/Genetic Toxicology and Environmental Mutagenesis745(1): 84–91.
46.
ShugartLTheodorakisC (1994) Environmental genotoxicity: probing the underlying mechanisms. Environmental Health Perspectives102(Suppl 12): 13.
47.
SinghSPKumariMKumariSI. (2013) Toxicity assessment of manganese oxide micro and nanoparticles in Wistar rats after 28 days of repeated oral exposure. Journal of Applied Toxicology33(10): 1165–1179.
48.
SinghNManshianBJenkinsGJS. (2009) NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. Biomaterials30(23): 3891–3914.
49.
SocciDJBjugstadKBJonesHC, et al. (1999) Evidence that oxidative stress is associated with the pathophysiology of inherited hydrocephalus in the H-Tx rat model. Experimental Neurology155(1): 109–117.
50.
SrivastavAKKumarMAnsariNG. (2016) A comprehensive toxicity study of zinc oxide nanoparticles versus their bulk in Wistar rats: toxicity study of zinc oxide nanoparticles. Human & Experimental Toxicology35(12): 1286–1304.
51.
SuzukiNSofikitisN (1999) Protective effects of antioxidants on testicular functions of varicocelized rats. Yonago Acta Medica42(7): 87–94.
52.
WangBFengWWangM. (2008) Acute toxicological impact of nano-and submicro-scaled zinc oxide powder on healthy adult mice. Journal of Nanoparticle Research10(2): 263–276.
53.
World Health Organization (2010) WHO Laboratory Manual for the Examination and Processing of Human Semen. 5th ed. Geneva: World Health Organization, pp. 21–26.
54.
XiaTKovochichMLiongM. (2008) Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties. ACS Nano2(10): 2121.
55.
YahyaNPuspitasariPLatiffNRA (2012) Hardness improvement of dental amalgam using zinc oxide and aluminum oxide nanoparticles. In: Characterization and Development of Biosystems and Biomaterials. OchsnerAndreasda SilvaLucas F. M.AltenbachHolm (eds), Advanced Structured Materials 29, Springer, Verlag Berlin, Heidelberg, pp. 9–32.
56.
YanLZhengYBZhaoF. (2012) Chemistry and physics of a single atomic layer: strategies and challenges for functionalization of graphene and graphene-based materials. Chemical Society Reviews41(1): 97–114.
57.
YangHLiuCYangD. (2009) Comparative study of cytotoxicity, oxidative stress and genotoxicity induced by four typical nanomaterials: the role of particle size, shape and composition. Journal of Applied Toxicology29(1): 69–78.
58.
YehFCYangRCBoyleT (1999) POPGENE version 1.31, University of Alberta, Canada.
59.
YoshidaYItohNSaitoY. (2004) Application of water-soluble radical initiator, 2, 2-azobis-[2-(2-imidazolin-2-yl) propane] dihydrochloride, to a study of oxidative stress. Free Radical Research38(4): 375–384.
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