Abstract
The present study was aimed to investigate the ability of cadmium (Cd) and nickel (Ni) to induce genotoxicity, cytotoxicity, and oxidative stress in bone marrow cells of male mice. Aneuploidy and chromosomal aberrations (CA) showed that Cd is a stronger mutagen than Ni. Cd and Ni increased significantly the incidences of micronucleated polychromatic erythrocytes (PCEs). Also, the ratio of polychromatic erythrocytes to normochromatic erythrocytes (PCE/NCE) suggests that treatment with higher doses of the two metals increased the cytotoxicity. Numerical chromosomal aberrations increased hypoploidy with the treatment which reached two to three times of the frequency of hyperploidy. The results showed that both Cd and Ni are aneugenic that act on kinetochores and cause malsegregation of chromosomes as well as being clastogenic. Both Cd and Ni increased single-break aberrations and also Cd and Ni were found to induce significant DNA damage in mouse bone marrow cells as assessed by the comet assay. In addition to the cytotoxicity results, biochemical analysis in bone marrow revealed a dose-dependent increase of oxidative stress markers. According to the results obtained, genotoxicity and cytotoxicity effects of cadmium and nickel in vivo are dose-dependent and are associated with oxidative stress and their combined effect is less than their expected additive effect, and it could be concluded that there are no synergistic effects resulting from the combined application of both metals.
Similar content being viewed by others
References
Zan NR, Datta SP, Rattan RK et al (2013) Prediction of the solubility of zinc, copper, nickel, cadmium, and lead in metal-contaminated soils. Environ Monit Assess 185:10015–10025
Permenter MG, Lewis JA, Jackson DA (2011) Exposure to nickel, chromium, or cadmium causes distinct changes in the gene expression patterns of a rat liver derived cell line. PLoS One 6(11):e27730
Othman MS, Nada A, Zaki HS et al (2014) Effect of Physalis peruviana L. On cadmium-induced testicular toxicity in rats. Biol Trace Elem Res. doi:10.1007/s12011-014-9955-1
Stohs SJ, Bagchi D (1995) Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med 18(2):321–336
Beyersmann D, Hartwig A (2008) Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms. Arch Toxicol 82(8):493–512
Hartwig A, Schwerdtle T (2002) Interactions by carcinogenic metal compounds with DNA repair processes: toxicological implications. Toxicol Lett 127(1–3):47–54
Stoner GD, Shimkin MB, Troxell MC et al (1976) Test for carcinogenicity of metallic compounds by the pulmonary tumor response in strain a mice. Cancer Res 36(5):1744–1747
Poirier LA, Theiss JC, Arnold LJ et al (1984) Inhibition by magnesium and calcium acetates of lead subacetate- and nickel acetate-induced lung tumors in strain a mice. Cancer Res 44(4):1520–1522
Savage JR (1976) Classification and relationships of induced chromosomal structural changes. J Med Genet 13(2):103–122
Singh NP, McCoy MT, Tice RR et al (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175(1):184–191
Collins AR (2014) Measuring oxidative damage to DNA and its repair with the comet assay. Biochim Biophys Acta 1840:794–800
Lowry OH, Rosebrough NJ, Farr AL et al (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193(1):265–275
El-Habit OH (2001) In vitro evaluation of the protective role of zinc and magnesium compounds on cadmium and nickel induced cytotoxicity and genotoxicity in male rats. J Egypt Ger Soc Zool 34C:83–97
Chen CY, Wang YF, Huang WR et al (2003) Nickel induces oxidative stress and genotoxicity in human lymphocytes. Toxicol Appl Pharmacol 189(3):153–159
El-Habit OH, Mussa E (2010) Clastogenic and aneugenic abilities of cadmium and nickel salts and their combinations in male mice. The UKEMS 33rd annual meeting P18:pp.113
Ayed-Boussema I, Rjiba K, Mnasri N et al (2012) Genotoxicity evaluation of dimethoate to experimental mice by micronucleus, chromosome aberration tests, and comet assay. Int J Toxicol 31(1):78–85
Sen P, Costa M (1985) Induction of chromosomal damage in Chinese hamster ovary cells by soluble and particulate nickel compounds: preferential fragmentation of the heterochromatic long arm of the x-chromosome by carcinogenic crystalline NiS particles. Cancer Res 45(5):2320–2325
Seoane AI, Dulout FN (2001) Genotoxic ability of cadmium, chromium and nickel salts studied by kinetochore staining in the cytokinesis-blocked micronucleus assay. Mutat Res 490(2):99–106
Khandelwal S, Tandon SK (1984) Effect of cadmium pretreatment on nickel toxicity. IARC Sci Publ 53:293–300
Fenech M (1993) The cytokinesis-block micronucleus technique and its application to genotoxicity studies in human populations. Environ Health Perspect 101(Suppl 3):101–107
Ciranni R, Antonetti M, Migliore L (1995) Vanadium salts induce cytogenetic effects in in vivo treated mice. Mutat Res 343(1):53–60
Desoize B (2003) Metals and metal compounds in carcinogenesis. In Vivo 17(6):529–539
Rehen SK, Yung YC, McCreight MP et al (2005) Constitutional aneuploidy in the normal human brain. J Neurosci 25(9):2176–2180
Ganmore I, Smooha G, Izraeli S (2009) Constitutional aneuploidy and cancer predisposition. Hum Mol Genet 18(R1):R84–R93
Merzenich H, Hartwig A, Ahrens W et al (2001) Biomonitoring on carcinogenic metals and oxidative DNA damage in a cross-sectional study. Cancer Epidemiol Biomarkers Prev 10(5):515–522
Chen CY, Lin TK, Chang YC et al (2010) Nickel(ii)-induced oxidative stress, apoptosis, g2/m arrest, and genotoxicity in normal rat kidney cells. Toxicol Appl Pharmacol 189:153–159
Güerci A, Seoane A, Dulout FN (2000) Aneugenic effects of some metal compounds assessed by chromosome counting in mrc-5 human cells. Mutat Res 469(1):35–40
Tice RR, Agurell E, Anderson D et al (2000) Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35(3):206–221
Wozniak K, Blasiak J (2002) Free radicals-mediated induction of oxidized DNA bases and DNA-protein cross-links by nickel chloride. Mutat Res 514(1–2):233–243
Kasprzak KS (2002) Oxidative DNA and protein damage in metal-induced toxicity and carcinogenesis. Free Radic Biol Med 32(10):958–967
Ognjanovic BI, Markovic SD, Ethordevic NZ et al (2010) Cadmium-induced lipid peroxidation and changes in antioxidant defense system in the rat testes: protective role of coenzyme Q(10) and vitamin e. Reprod Toxicol 29(2):191–197
El-Maraghy SA, Gad MZ, Fahim AT et al (2001) Effect of cadmium and aluminum intake on the antioxidant status and lipid peroxidation in rat tissues. J Biochem Mol Toxicol 15(4):207–214
Das KK, Das SN, DasGupta S (2001) The influence of ascorbic acid on nickel-induced hepatic lipid peroxidation in rats. J Basic Clin Physiol Pharmacol 12(3):187–195
Chlubek D, Grucka-Mamczar E, Birkner E et al (2003) Activity of pancreatic antioxidative enzymes and malondialdehyde concentrations in rats with hyperglycemia caused by fluoride intoxication. J Trace Elem Med Biol 17(1):57–60
Rana SV, Verma S (1996) Protective effects of GSH, vitamin E, and selenium on lipid peroxidation in cadmium-fed rats. Biol Trace Elem Res 51(2):161–168
Chakrabarti SK, Bai C (1999) Role of oxidative stress in nickel chloride-induced cell injury in rat renal cortical slices. Biochem Pharmacol 58(9):1501–1510
Das KK, Das SN, Dhundasi SA (2008) Nickel, its adverse health effects & oxidative stress. Indian J Med Res 128(4):412–425
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
El-Habit, O.H., Abdel Moneim, A.E. Testing the Genotoxicity, Cytotoxicity, and Oxidative Stress of Cadmium and Nickel and Their Additive Effect in Male Mice. Biol Trace Elem Res 159, 364–372 (2014). https://doi.org/10.1007/s12011-014-0016-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12011-014-0016-6