Skip to main content
SpringerLink
Log in

Comparative Study of Cytotoxicity, DNA Damage and Oxidative Stress Induced by Heavy Metals Cd(II), Hg(II) and Cr(III) in Yeast

  • Published:
Current Microbiology Aims and scope Submit manuscript

Abstract

Wide range of applications of heavy metals and improperly discarded their castoffs possess serious threats to environment and human health. In this study, cytotoxicity, DNA damage and oxidative stress induced by Cd(II), Hg(II) and Cr(III) were comparatively studied in yeast Saccharomyces cerevisiae. Cd(II), Hg(II), and Cr(III) all produced strong cytotoxicity resulting in growth inhibition and cell mortality to varying degrees (Hg(II) > Cd(II) > Cr(III)). Hg(II) produced more oxidative stress. Cr(III) caused more serious DNA damage in vitro. Cd(II) also caused both obvious DNA damage and oxidative stress at higher concentration, but not as efficiently as Cd(II) and Hg(II). A further null mutation sensitivity assay showed that the relative sensitivity of rad1∆ to the metals was Cr(III) > Cd(II) > Hg(II), and that of trx1∆ to the metals was Hg(II) > Cd(II) > Cr(III). These data provide a clear evidence that the Cr(III) can cause significant DNA damage and potential genotoxicity; Hg(II) can strongly inhibit SOD activity, produce lipid peroxidation and cause serious membrane injury, suggesting these heavy metals can cause different toxic effects in different ways.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Gheju M, Balcu I (2017) Assisted green remediation of chromium pollution. J Environ Manag 203:920–924

    Article  CAS  Google Scholar 

  2. Chen Y, Mao H, Ma J, Wu N, Zhang C, Su Y, Zhang Z, Yuan M, Zhang H, Zeng X (2018) Biomonitoring chromium III or VI soluble pollution by moss chlorophyll fluorescence. Chemosphere 194:220–228

    Article  CAS  Google Scholar 

  3. Zimta A, Schitcu V, Gurzau E, Stavaru C, Manda G, Szedlacsek SE, Berindanneagoe I (2019) Biological and molecular modifications induced by cadmium and arsenic during breast and prostate cancer development. Environ Res 178:108700

    Article  CAS  Google Scholar 

  4. Kumari S, Amit JR, Mishra N, Singh DK (2020) Recent developments in environmental mercury bioremediation and its toxicity: a review. Environ Nanotechnol Monit Manag 13:100283. https://doi.org/10.1016/j.enmm.2020.100283

    Article  Google Scholar 

  5. Gundacker C, Frohlich S, Grafrohrmeister K, Eibenberger B, Jessenig V, Gicic D, Prinz S, Wittmann KJ, Zeisler H, Vallant B (2010) Perinatal lead and mercury exposure in Austria. Sci Total Environ 408(23):5744–5749

    Article  CAS  Google Scholar 

  6. Desmarias TL, Costa M (2019) Mechanisms of chromium-induced toxicity. Curr Opin Toxicol 14:1–7

    Article  Google Scholar 

  7. Zhitkovich A (2005) Importance of chromium−DNA adducts in mutagenicity and toxicity of chromium(VI). Chem Res Toxicol 1(18):3–11. https://doi.org/10.1021/tx049774+

    Article  CAS  Google Scholar 

  8. Puzon GJ, Tokala RK, Zhang H, Yonge D, Peyton BM, Xun L (2008) Mobility and recalcitrance of organo–chromium(III) complexes. Chemosphere 70(11):2054–2059. https://doi.org/10.1016/j.chemosphere.2007.09.010

    Article  CAS  PubMed  Google Scholar 

  9. Nargund AM, Avery SV, Houghton JE (2008) Cadmium induces a heterogeneous and caspase-dependent apoptotic response in Saccharomyces cerevisiae. Apoptosis 13(6):811–821

    Article  CAS  Google Scholar 

  10. Kumar KMK, Kumar MN, Patil RH, Nagesh R, Hegde SM, Kavya K, Babu RL, Ramesh GT, Sharma SC (2016) Cadmium induces oxidative stress and apoptosis in lung epithelial cells. Toxicol Mech Methods 26(9):658–666

    Article  Google Scholar 

  11. Nanda R, Agrawal V (2018) Piriformospora indica, an excellent system for heavy metal sequestration and amelioration of oxidative stress and DNA damage in Cassia angustifolia Vahl under copper stress. Ecotoxicol Environ Saf 156:409–419. https://doi.org/10.1016/j.ecoenv.2018.03.016

    Article  CAS  PubMed  Google Scholar 

  12. Huang Z, Yu Y, Fang Z, Deng Y, Shen Y, Shi P (2018) OLE1 reduces cadmium-induced oxidative damage in Saccharomyces cerevisiae. FEMS Microbiol Lett. https://doi.org/10.1093/femsle/fny193

    Article  PubMed  Google Scholar 

  13. Fang Z, Zhao M, Zhen H, Chen L, Shi P, Huang Z (2014) Genotoxicity of tri- and hexavalent chromium compounds in vivo and their modes of action on DNA damage in vitro. PLoS ONE 9(8):e103194

    Article  Google Scholar 

  14. Malik MA, Althabaiti SA, Malik MA (2012) Synthesis, structure optimization and antifungal screening of novel tetrazole ring bearing acyl-hydrazones. Int J Mol Sci 13(9):10880–10898

    Article  CAS  Google Scholar 

  15. Fang Z, Chen Z, Wang S, Shi P, Shen Y, Zhang Y, Xiao J, Huang Z (2016) Overexpression of OLE1 enhances cytoplasmic membrane stability and confers resistance to cadmium in Saccharomyces cerevisiae. Appl Environ Microbiol. https://doi.org/10.1128/AEM.2319-16

    Article  PubMed  PubMed Central  Google Scholar 

  16. Beauchamp C, Fridovich I (1971) Superoxide dismutase: improved assays and an assay applicable to acrylamide gels. Anal Biochem 44(1):276–287

    Article  CAS  Google Scholar 

  17. Huang Z, Kuang X, Chen Z, Fang Z, Wang S, Shi P (2014) Comparative studies of tri- and hexavalent chromium cytotoxicity and their effects on oxidative state of Saccharomyces cerevisiae cells. Curr Microbiol 68(4):448–456

    Article  CAS  Google Scholar 

  18. Wang J, Zhang Y, Fang Z, Sun L, Wang Y, Liu Y, Xu D, Nie F, Gooneratne R (2019) Oleic acid alleviates cadmium-induced oxidative damage in rat by its radicals scavenging activity. Biol Trace Elem Res 190(1):95–100

    Article  CAS  Google Scholar 

  19. Kuang X, Fang Z, Wang S, Shi P, Huang Z (2015) Effects of cadmium on intracellular cation homoeostasis in the yeast Saccharomyces cerevisiae. Toxicol Environ Chem 97(7):922–930. https://doi.org/10.1080/02772248.2015.1074689

    Article  CAS  Google Scholar 

  20. Yiin S, Chern C, Sheu J, Lin T (1999) Cadmium induced lipid peroxidation in rat testes and protection by selenium. Biometals 12(4):353–359

    Article  CAS  Google Scholar 

  21. Gargioni R, Filipak Neto F, Buchi DF, Randi MAF, Franco CRC, Paludo KS, Pelletier É, Ferraro MVM, Cestari MM, Bussolaro D, Oliveira Ribeiro CA (2006) Cell death and DNA damage in peritoneal macrophages of mice (Mus musculus) exposed to inorganic lead. Cell Biol Int 30(7):615–623. https://doi.org/10.1016/j.cellbi.2006.03.010

    Article  CAS  PubMed  Google Scholar 

  22. Zhang X, Kuang X, Cao F, Chen R, Fang Z, Liu W, Shi P, Wang H, Shen Y, Huang Z (2020) Effect of cadmium on mRNA mistranslation in Saccharomyces cerevisiae. J Basic Microbiol 60(4):372–379

    Article  CAS  Google Scholar 

  23. Farrell RP, Judd RJ, Lay PA, Dixon NE, Baker RSU, Bonin AM (1989) Chromium(V)-induced cleavage of DNA: are chromium(V) complexes the active carcinogens in chromium(VI)-induced cancers? Chem Res Toxicol 2(4):227–229

    Article  CAS  Google Scholar 

  24. Garrido EO, Grant CM (2002) Role of thioredoxins in the response of Saccharomyces cerevisiae to oxidative stress induced by hydroperoxides. Mol Microbiol 43(4):993–1003

    Article  CAS  Google Scholar 

  25. Unk I, Haracska L, Prakash S, Prakash L (2001) 3′-Phosphodiesterase and 3′→5′ exonuclease activities of yeast apn2 protein and requirement of these activities for repair of oxidative DNA damage. Mol Cell Biol 21(5):1656–1661

    Article  CAS  Google Scholar 

  26. Prakash S, Prakash L (2000) Nucleotide excision repair in yeast. Mutat Res 451(1):13–24

    Article  CAS  Google Scholar 

  27. Herrero E, Ros J, Belli G, Cabiscol E (2008) Redox control and oxidative stress in yeast cells. Biochim Biophys Acta 1780(11):1217–1235

    Article  CAS  Google Scholar 

  28. Picazo C, McDonagh B, Peinado J, Bárcena JA, Matallana E, Aranda A (2019) Saccharomyces cerevisiae cytosolic thioredoxins control glycolysis, lipid metabolism, and protein biosynthesis under wine-making conditions. Appl Environ Microbiol 85(7):e02953-02918. https://doi.org/10.1128/aem.02953-18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ramotar D, Popoff SC, Gralla EB, Demple B (1991) Cellular role of yeast Apn1 apurinic endonuclease/3′-diesterase: repair of oxidative and alkylation DNA damage and control of spontaneous mutation. Mol Cell Biol 11(9):4537–4544. https://doi.org/10.1128/mcb.11.9.4537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ho R, Rachek LI, Xu Y, Kelley MR, LeDoux SP, Wilson GL (2007) Yeast apurinic/apyrimidinic endonuclease Apn1 protects mammalian neuronal cell line from oxidative stress. J Neurochem 102(1):13–24. https://doi.org/10.1111/j.1471-4159.2007.04490.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Şener G, Şehirli AÖ, Ayanogˇlu-Dülger G (2003) Melatonin protects against mercury(II)-induced oxidative tissue damage in rats. Pharmacol Toxicol 93(6):290–296. https://doi.org/10.1111/j.1600-0773.2003.pto930607.x

    Article  PubMed  Google Scholar 

  32. Elblehi SS, Hafez MH, El-Sayed YS (2019) L-α-Phosphatidylcholine attenuates mercury-induced hepato-renal damage through suppressing oxidative stress and inflammation. Environ Sci Pollut Res 26(9):9333–9342. https://doi.org/10.1007/s11356-019-04395-9

    Article  CAS  Google Scholar 

  33. Dazy M, Masfaraud JF, Férard JF (2009) Induction of oxidative stress biomarkers associated with heavy metal stress in Fontinalis antipyretica Hedw. Chemosphere 75(3):297–302. https://doi.org/10.1016/j.chemosphere.2008.12.045

    Article  CAS  PubMed  Google Scholar 

  34. Shinyashiki M, Kumagai Y, Homma-Takeda S, Nagafune J, Takasawa N, Suzuki J, Matsuzaki I, Satoh S, Sagai M, Shimojo N (1996) Selective inhibition of the mouse brain Mn-SOD by methylmercury. Environ Toxicol Pharmacol 2(4):359–366. https://doi.org/10.1016/S1382-6689(96)00070-1

    Article  CAS  PubMed  Google Scholar 

  35. Dey SK, Jena PP, Kundu S (2009) Antioxidative efficiency of Triticum aestivum L. exposed to chromium stress. J Environ Biol 30(4):539

    CAS  PubMed  Google Scholar 

  36. Dixit V, Pandey V, Shyam R (2002) Chromium ions inactivate electron transport and enhance superoxide generation in vivo in pea Pisum sativum L. cv. Azad root mitochondria. Plant Cell Environ 25(5):687–693

    Article  CAS  Google Scholar 

  37. Xiao F, Li Y, Dai L, Deng Y, Zou Y, Li P, Yang Y, Zhong C (2012) Hexavalent chromium targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent caspase-3 activation in L-02 hepatocytes. Int J Mol Med 30(3):629–635. https://doi.org/10.3892/ijmm.2012.1031

    Article  CAS  PubMed  Google Scholar 

  38. Polykretis P, Cencetti F, Donati C, Luchinat E, Banci L (2019) Cadmium effects on superoxide dismutase 1 in human cells revealed by NMR. Redox Biol 21:101102. https://doi.org/10.1016/j.redox.2019.101102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Stohs SJ, Bagchi D, Hassoun E, Bagchi M (2001) Oxidative mechanisms in the toxicity of chromium and cadmium ions. J Environ Pathol Toxicol Oncol 20(2):12. https://doi.org/10.1615/JEnvironPatholToxicolOncol.v20.i2.10

    Article  Google Scholar 

  40. Zecevic A, Menard HL, Gurel V, Hagan E, Decaro R, Zhitkovich A (2009) WRN helicase promotes repair of DNA double-strand breaks caused by aberrant mismatch repair of chromium-DNA adducts. Cell Cycle 8(17):2769–2778

    Article  CAS  Google Scholar 

  41. Reynolds M, Petersonroth E, Bespalov I, Johnston T, Gurel V, Menard HL, Zhitkovich A (2009) Rapid DNA double-strand breaks resulting from processing of Cr-DNA cross-links by both MutS dimers. Cancer Res 69(3):1071–1079

    Article  CAS  Google Scholar 

  42. Arakawa H, Ahmad R, Naoui M, Tajmirriahi HA (2000) A comparative study of calf thymus DNA binding to Cr(III) and Cr(VI) Ions: evidence for the guanine N-7-chromium-phosphate chelate formation. J Biol Chem 275(14):10150–10153

    Article  CAS  Google Scholar 

  43. 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/Genet Toxicol Environ Mutagen 490(2):99–106. https://doi.org/10.1016/S1383-5718(00)00145-5

    Article  CAS  Google Scholar 

  44. Joseph P (2009) Mechanisms of cadmium carcinogenesis. Toxicol Appl Pharmacol 238(3):272–279

    Article  CAS  Google Scholar 

  45. Waalkes MP, Poirier LA (1984) In vitro cadmium-DNA interactions: cooperativity of cadmium binding and competitive antagonism by calcium, magnesium, and zinc. Toxicol Appl Pharmacol 75(3):539–546. https://doi.org/10.1016/0041-008X(84)90190-X

    Article  CAS  PubMed  Google Scholar 

  46. Dunpall R, Nejo AA, Pullabhotla VSR, Opoku AR, Revaprasadu N, Shonhai A (2012) An in vitro assessment of the interaction of cadmium selenide quantum dots with DNA, iron, and blood platelets. IUBMB Life 64(12):995–1002. https://doi.org/10.1002/iub.1100

    Article  CAS  PubMed  Google Scholar 

  47. Dally H, Hartwig A (1997) Induction and repair inhibition of oxidative DNA damage by nickel(II) and cadmium(II) in mammalian cells. Carcinogenesis 18(5):1021–1026

    Article  CAS  Google Scholar 

  48. Bagchi D, Joshi SS, Bagchi M, Balmoori J, Benner EJ, Kuszynski CA, Stohs SJ (2000) Cadmium- and chromium-induced oxidative stress, DNA damage, and apoptotic cell death in cultured human chronic myelogenous leukemic K562 cells, promyelocytic leukemic HL-60 cells, and normal human peripheral blood mononuclear cells. J Biochem Mol Toxicol 14(1):33–41. https://doi.org/10.1002/(sici)1099-0461(2000)14:1%3c33::aid-jbt5%3e3.0.co;2-y

    Article  CAS  PubMed  Google Scholar 

  49. Onyido I, Norris AR, Buncel E (2004) Biomolecule−mercury interactions: modalities of DNA base−mercury binding mechanisms. Remediat Strateg Chem Rev 104(12):5911–5930. https://doi.org/10.1021/cr030443w

    Article  CAS  Google Scholar 

  50. Sljivic Husejnovic M, Bergant M, Jankovic S, Zizek S, Smajlovic A, Softic A, Music O, Antonijevic B (2018) Assessment of Pb, Cd and Hg soil contamination and its potential to cause cytotoxic and genotoxic effects in human cell lines (CaCo-2 and HaCaT). Environ Geochem Health 40(4):1557–1572. https://doi.org/10.1007/s10653-018-0071-6

    Article  CAS  PubMed  Google Scholar 

  51. Tsuzuki K, Sugiyama M, Haramaki N (1994) DNA single-strand breaks and cytotoxicity induced by chromate(VI), cadmium(II), and mercury(II) in hydrogen peroxide-resistant cell lines. Environ Health Perspect 102(3):341–342. https://doi.org/10.1289/ehp.94102s3341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Skipper A, Sims JN, Yedjou CG, Tchounwou PB (2016) Cadmium chloride induces DNA damage and apoptosis of human liver carcinoma cells via oxidative stress. Int J Environ Res Public Health 13(1):88

    Article  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (No. 31701706), the Program for Scientific Research Start-up Funds of the Guangdong Ocean University (No. R17102), Characteristic Innovation Project of Guangdong Province (No. 2018KTSCX089) and Guangdong Basic and Applied Basic Research Foundation (Nos. 2019A1515010809 and 2021A1515012443). The design of the study: the National Natural Science Foundation of China (No. 31701706); data collection, interpretation of data: the National Natural Science Foundation of China (No. 31701706), the Program for Scientific Research Start-up Funds of the Guangdong Ocean University (No. R17102), Characteristic Innovation Project of Guangdong Province (No. 2018KTSCX089), Guangdong Basic and Applied Basic Research Foundation (Nos. 2019A1515010809 and 2021A1515012443); writing the manuscript: the Program for Scientific Research Start-up Funds of the Guangdong Ocean University (No. R17102).

Author information

Authors and Affiliations

  1. College of Food Science and Technology, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology, Research Center of Marine Food, Key Laboratory of Advanced Processing of Aquatic Products of Guangdong Higher Education Institution, Cunjin College, Guangdong Ocean University, Zhanjiang, 524088, China

    Jingwen Wang, Zhijia Fang, Jian Gao, Lijun Sun, Yaling Wang & Ying Liu

  2. Department of Wine, Food and Molecular Biosciences, Lincoln University, Lincoln, Canterbury, 7647, New Zealand

    Ravi Gooneratne

Authors
  1. Jingwen Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhijia Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jian Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lijun Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yaling Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ying Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ravi Gooneratne
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis: were performed by JW and ZF. The first draft of the manuscript: was written by JW and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zhijia Fang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, J., Fang, Z., Gao, J. et al. Comparative Study of Cytotoxicity, DNA Damage and Oxidative Stress Induced by Heavy Metals Cd(II), Hg(II) and Cr(III) in Yeast. Curr Microbiol 78, 1856–1863 (2021). https://doi.org/10.1007/s00284-021-02454-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00284-021-02454-4

Search

Navigation