Skip to main content
Log in

Testing the Genotoxicity, Cytotoxicity, and Oxidative Stress of Cadmium and Nickel and Their Additive Effect in Male Mice

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. 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

    Article  CAS  PubMed  Google Scholar 

  2. 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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. 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

    PubMed  Google Scholar 

  4. Stohs SJ, Bagchi D (1995) Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med 18(2):321–336

    Article  CAS  PubMed  Google Scholar 

  5. Beyersmann D, Hartwig A (2008) Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms. Arch Toxicol 82(8):493–512

    Article  CAS  PubMed  Google Scholar 

  6. Hartwig A, Schwerdtle T (2002) Interactions by carcinogenic metal compounds with DNA repair processes: toxicological implications. Toxicol Lett 127(1–3):47–54

    Article  CAS  PubMed  Google Scholar 

  7. 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

    CAS  PubMed  Google Scholar 

  8. 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

    CAS  PubMed  Google Scholar 

  9. Savage JR (1976) Classification and relationships of induced chromosomal structural changes. J Med Genet 13(2):103–122

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. 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

    Article  CAS  PubMed  Google Scholar 

  11. Collins AR (2014) Measuring oxidative damage to DNA and its repair with the comet assay. Biochim Biophys Acta 1840:794–800

    Article  CAS  PubMed  Google Scholar 

  12. Lowry OH, Rosebrough NJ, Farr AL et al (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193(1):265–275

    CAS  PubMed  Google Scholar 

  13. 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

    Google Scholar 

  14. 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

    Article  CAS  PubMed  Google Scholar 

  15. 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

  16. 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

    Article  CAS  PubMed  Google Scholar 

  17. 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

    CAS  PubMed  Google Scholar 

  18. 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

    Article  CAS  PubMed  Google Scholar 

  19. Khandelwal S, Tandon SK (1984) Effect of cadmium pretreatment on nickel toxicity. IARC Sci Publ 53:293–300

    CAS  PubMed  Google Scholar 

  20. 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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Ciranni R, Antonetti M, Migliore L (1995) Vanadium salts induce cytogenetic effects in in vivo treated mice. Mutat Res 343(1):53–60

    Article  CAS  PubMed  Google Scholar 

  22. Desoize B (2003) Metals and metal compounds in carcinogenesis. In Vivo 17(6):529–539

    CAS  PubMed  Google Scholar 

  23. Rehen SK, Yung YC, McCreight MP et al (2005) Constitutional aneuploidy in the normal human brain. J Neurosci 25(9):2176–2180

    Article  CAS  PubMed  Google Scholar 

  24. Ganmore I, Smooha G, Izraeli S (2009) Constitutional aneuploidy and cancer predisposition. Hum Mol Genet 18(R1):R84–R93

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. 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

    CAS  PubMed  Google Scholar 

  26. 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

    Article  Google Scholar 

  27. 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

    Article  PubMed  Google Scholar 

  28. 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

    Article  CAS  PubMed  Google Scholar 

  29. 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

    Article  CAS  PubMed  Google Scholar 

  30. Kasprzak KS (2002) Oxidative DNA and protein damage in metal-induced toxicity and carcinogenesis. Free Radic Biol Med 32(10):958–967

    Article  CAS  PubMed  Google Scholar 

  31. 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

    Article  CAS  PubMed  Google Scholar 

  32. 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

    Article  CAS  PubMed  Google Scholar 

  33. 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

    Article  CAS  PubMed  Google Scholar 

  34. 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

    Article  CAS  PubMed  Google Scholar 

  35. 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

    Article  CAS  PubMed  Google Scholar 

  36. 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

    Article  CAS  PubMed  Google Scholar 

  37. Das KK, Das SN, Dhundasi SA (2008) Nickel, its adverse health effects & oxidative stress. Indian J Med Res 128(4):412–425

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ahmed E. Abdel Moneim.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-014-0016-6

Keywords

Navigation