Skip to main content
Log in

Predicting ZnO nanoparticle and ZnSO4 toxicity from zebrafish embryo gene expression

  • Original Paper
  • Published:
Molecular & Cellular Toxicology Aims and scope Submit manuscript

Abstract

The potential to replace the early-life-stage toxicity test (ELS) with the gene expression toxicity test in zebrafish (Danio rerio) embryos (gene-DarT) was evaluated. We compared the lowest-observable- effect concentrations (LOECs) for each. For ELS, zebrafish were exposed to ZnO nanoparticles (NPs) and ZnSO4 at 0-0.25 and 0-16 mg/L, respectively, for 28 d. For 48-h gene-DarT tests, expression of potential marker genes (opioid growth factor receptor-like 2 [ogfrl2], cytochrome b5 domain-containing 1 [cyb5d1], and intelectin 2 [intl2] for ZnO NPs and trace amine-associated receptor 10c, CaM kinase-like vesicle-associated, and interferon regulatory factor 2a [irf2a] for ZnSO4) was investigated. The ELS LOECs for ZnO NP and ZnSO4 were 0.016 and 1 mg/L, respectively. Gene-DartT cyb5d1 and irf2a LOECs were 4-16 times lower than ELS LOECs. Gene-DarT ogfrl2 and intl2 and ELS LOECs were similar. Our results suggest the gene-DarT is an effective alternative for predicting ZnO NP and ZnSO4 LOECs.

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.

Similar content being viewed by others

References

  1. Ramirez, T. et al. Knowledge sharing to facilitate regulatory decision-making in regard to alternatives to animal testing: Report of an EPAA workshop. Regul Toxicol Pharmacol 73: 210–226 (2015).

    Article  PubMed  Google Scholar 

  2. Voelker, D. et al. Differential gene expression as a toxicant-sensitive endpoint in zebrafish embryos and larvae. Aquat Toxicol 81: 355–364 (2007).

    Article  CAS  PubMed  Google Scholar 

  3. Nagel, R. DarT: The embryo test with the zebrafish Danio rerio - a general model in ecotoxicology and toxicology. Altex 19 Suppl 1: 38–48 (2002).

    Google Scholar 

  4. OECD Guidelines for the Testing of Chemicals. No. 210: Fish, Early-life Stage Toxicity Test, Organisation for Economic Cooperation and Development, www.oecd-ilibrary.org/OECD210.pdf (2013).

  5. Weil, M., Scholz, S., Zimmer, M., Sacher, F. & Duis, K. Gene expression analysis in zebrafish embryos: a potential approach to predict effect concentrations in the fish early life stage test. Environ Toxicol Chem 28: 1970–1978 (2009).

    Article  CAS  PubMed  Google Scholar 

  6. Chen, R. et al. Endoplasmic reticulum stress induced by zinc oxide nanoparticles is an earlier biomarker for nanotoxicological evaluation. ACS Nano 8: 2562–2574 (2014).

    Article  CAS  PubMed  Google Scholar 

  7. Hua, J., Vijver, M. G., Richardson, M. K., Ahmad, F. & Peijnenburg, W. J. Particle-specific toxic effects of differently shaped zinc oxide nanoparticles to zebrafish embryos (Danio rerio). Environ Toxicol Chem 33: 2859–2868 (2014).

    Article  CAS  PubMed  Google Scholar 

  8. Zhao, X., Wang, S., Wu, Y., You, H. & Lv, L. Acute ZnO nanoparticles exposure induces developmental toxicity, oxidative stress and DNA damage in embryolarval zebrafish. Aquat Toxicol 136-137:49–59 (2013).

    Article  CAS  PubMed  Google Scholar 

  9. Zhu, X. et al. Comparative toxicity of several metal oxide nanoparticle aqueous suspensions to zebrafish (Danio rerio) early developmental stage. J Environ Sci Health, Part A: Toxic/Hazard Subst Environ Eng 43: 278–284 (2008).

    Article  CAS  Google Scholar 

  10. Yu, L., Fang, T., Xiong, D., Zhu, W. & Sima, X. Comparative toxicity of nano-ZnO and bulk ZnO suspensions to zebrafish and the effects of sedimentation, ·OH production and particle dissolution in distilled water. J Environ Monit 13: 1975–1982 (2011).

    Article  CAS  PubMed  Google Scholar 

  11. Watanabe, Y., Oozeki, Y. & Kitagawa, D. Larval parameters determining preschooling juvenile production of pacific saury (Cololabis saira) in the northwestern Pacific. Can J Fish Aquat Sci 54: 1067–1076 (1997).

    Article  Google Scholar 

  12. Zheng J. L. et al. Effect of waterborne zinc exposure on metal accumulation, enzymatic activities and histology of Synechogobius hasta. Ecotoxicol Environ Saf 74: 1864–1873 (2011).

    Article  CAS  PubMed  Google Scholar 

  13. Ju, S. M., Lee, J. W., Jin, Y. G., Yu, J. & Lee, J. S. Effect of zinc bioaccumulation on survival rate, activity, growth and organ structure of the equilateral venus, Gomphina veneriformis (Bivalvia: Veneridae). J Environ Toxicol 21: 115–126 (2006).

    Google Scholar 

  14. Felix, L. C., Ortega, V. A., Ede, J. D. & Goss, G. G. Physicochemical characteristics of polymer-coated metal-oxide nanoparticles and their toxicological effects on zebrafish (Danio rerio) development. Environ Sci Technol 47: 6589–6596 (2013).

    Article  CAS  PubMed  Google Scholar 

  15. Wang, J., Zhu, X., Chen, Y. & Chang, Y. Application of embryonic and adult zebrafish for nanotoxicity assess ment. Methods Mol Biol 926: 317–329 (2012).

    Article  CAS  PubMed  Google Scholar 

  16. Embry, M. R. et al. The fish embryo toxicity test as an animal alternative method in hazard and risk assessment and scientific research. Aquat Toxicol 97: 79–87 (2010).

    Article  CAS  PubMed  Google Scholar 

  17. Tuomela, S. et al. Gene expression profiling of immunecompetent human cells exposed to engineered zinc oxide or titanium dioxide nanoparticles. PLoS One 8: e68415 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Mironava, T., Hadjiargyrou, M., Simon, M., Jurukovski, V. & Rafailovich, M. H. Gold nanoparticles cellular toxicity and recovery: effect of size, concentration and exposure time. Nanotoxicology 4: 120–137 (2010).

    Article  CAS  PubMed  Google Scholar 

  19. Toxnet, http://toxnet.nlm.nih.gov (2016).

  20. Cheng, F., McLaughlin, P. J., Verderame, M. F. & Zagon, I. S. The OGF-OGFr axis utilizes the p16INK4a and p21WAF1/CIP1 pathways to restrict normal cell proliferation. Mol Biol Cell 20: 319–327 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lin, B. et al. Characterization and comparative analyses of zebrafish intelectins: highly conserved sequences, diversified structures and functions. Fish Shellfish Immunol 26: 396–405 (2009).

    Article  CAS  PubMed  Google Scholar 

  22. Huang, B., Qi, Z. T., Xu, Z. & Nie, P. Global characterization of interferon regulatory factor (IRF) genes in vertebrates: Glimpse of the diversification in evolution. BMC Immunol 11:22 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Takano, T. et al. The two channel catfish intelectin genes exhibit highly differential patterns of tissue expression and regulation after infection with Edwardsiella ictaluri. Dev Comp Immunol 32: 693–705 (2008).

    Article  CAS  PubMed  Google Scholar 

  24. Pan, Y., Kaiguo, M., Razak, Z., Westwood, J. T. & Gerlai, R. Chronic alcohol exposure induced gene expression changes in the zebrafish brain. Behav Brain Res 16: 66–76 (2011).

    Article  Google Scholar 

  25. Li, F. F., Li, W. Q. & Jing, Q. G protein-coupled receptors in vascular development. Yi Chuan 35: 459–467 (2013) (in Chinese).

    Article  CAS  PubMed  Google Scholar 

  26. Turin, L. A spectroscopic mechanism for primary olfactory reception. Chem Senses 21: 773–791 (1996).

    Article  CAS  PubMed  Google Scholar 

  27. camkvl CaM kinase-like vesicle-associated, like [Danio rerio (zebrafish)], NCBI, www.ncbi.nlm.nih.gov/gene/ 553431 (2016).

  28. van de Vijver, M. J. et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347: 1999–2009 (2002).

    Article  PubMed  Google Scholar 

  29. OECD Guidelines for the Testing of Chemicals, Section 2, Test No. 236: Fish Embryo Acute Toxicity (FET) Test, http://www.oecd-ilibrary.org/environment/test-no-236-fish-embryo-acute-toxicity-fet-test_9789264203709-en (2013).

  30. OECD Guidelines for the Testing of Chemicals, Section 2, Test No. 210: Fish, Early-life Stage Toxicity Test, http://www.oecd-ilibrary.org/environment/test-no-210-fish-early-life-stage-toxicity-test_9789264203785-en (2013).

  31. Choi, J., Kim, R. O., Yoon, S. & Kim, W. K. Development toxicity of zinc oxide nanoparticles to zebrafish (Danio rerio): a transcriptomic analysis. PLoS One 11: e0160763 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Gene Expression Omnibus, www.ncbi.nlm.nih.gov/ geo/index.cgi (2016).

  33. Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCt method. Methods 25: 402–408 (2001).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Woo-Keun Kim.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Choi, J.S., Song, J., Yoon, S. et al. Predicting ZnO nanoparticle and ZnSO4 toxicity from zebrafish embryo gene expression. Mol. Cell. Toxicol. 14, 19–26 (2018). https://doi.org/10.1007/s13273-018-0003-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13273-018-0003-7

Keywords

Navigation