Oxidant-Antioxidant Status and c-myc Expression in BPA- and DEHP-Exposed Zebrafish Embryos

Year 2017, , 26 - 30, 27.12.2017

Unsal Veli Ustundag İsmail Unal Perihan Seda Ates Ahmet Ata Alturfan Turkan Yigitbasi Ebru Emekli Alturfan

https://doi.org/10.5152/EurJBiol.2017.1705

Abstract

Di-(2-ethylhexyl)-phthalate
(DEHP) is used in polyethylene terephthalate plastics and bisphenol-A (BPA) is
used to make polycarbonate plastics. The health-concerning effects of DEHP and
BPA indicate their potential toxic effects. The Wnt/β-catenin signaling pathway is necessary for embryonic
development. The c-MYC proto-oncogene (MYC) has been identified as a Wnt/β-catenin target gene, and MYC is a transcription
factor that regulates the expression of many gene products related to cell
proliferation, growth, differentiation, and apoptosis. Activation and
overexpression of the MYC gene has been reported in many human cancers and
during tumorigenesis. The aim of this study was to investigate the relationship
between oxidant-antioxidant balance and c-myc in BPA- and DEHP-exposed
zebrafish embryos. The real-time-polymerase chain reaction was used to
determine c-myc expression. Lipid peroxidation (LPO), nitric oxide (NO) levels,
and superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities
were determined in homogenates prepared from pooled embryo samples. Increased
expression of c-myc and decreased GST activity were observed in the BPA and
DEHP groups. NO levels increased and SOD activity decreased in the BPA group,
whereas LPO increased in the DEHP group. Disruption of oxidant-antioxidant
balance in DEHP- and BPA-exposed zebrafish embryos was associated with
increased c-myc expression and may be an important mechanism for the toxic
effects of these chemicals. 

Keywords

Di(2-ethylhexyl) phthalate, bisphenol A, oxidant-antioxidant balance, c-myc, zebrafish embryo

References

• 1. Kincha CD, Ibhazehiebo K, Jeong JH, Habibia HR, Kurrasch DM. Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish. Proc Nat Acad Sci 2015; 112(5): 1475-80. 2. Wan HT, Leung PY, Zhao YG, Wei X, Wong MH, Wong CK. Blood plasma concentrations of endocrine disrupting chemicals in Hong Kong populations. J Hazard Mater 2013; 261: 763-9. 3. Uren-Webster TM, Lewis C, Filby A, Paull GC, Santos EM. Mechanisms of toxicity of di(2-ethylhexyl) phthalate on the reproductive health of male zebrafish. Aquat Toxicol 2010; 99(3): 360-9. 4. Akyüz S, Yarat A, Egil E. Dental materials containing bisphenol-A: current approach. Clin Exp Health Sci 2011; 1(3): 190-5. 5. Alonso-Magdalena P, Vieira E, Soriano S, Menes L, Burks D, Quesada I, et al. Bisphenol A exposure during pregnancy disrupts glucose homeostasis in mothers and adult male offspring. Environ Health Perspect 2010; 118(9): 1243-50. 6. Adewale HB, Todd KL, Mickens JA, Patisaul HB. The impact of neonatal bisphenol-A exposure on sexually dimorphic hypothalamic nuclei in the female rat. Neurotoxicology 2011; 32(1): 38-49. 7. Huang H, He X. Wnt/beta-catenin signaling: new (and old) players and new insights. Curr Opin Cell Biol 2008; 20(2): 119-25. 8. Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 2004; 20: 781-810. 9. Stuppia L, Franzago, Ballerini P, Gatta V, Antonucci I. Epigenetics and male reproduction: the consequences of paternal lifestyle on fertility, embryo development, and children lifetime health. Clin Epigenetics 2015; 7: 120. 10. Casey SC, Tong L, Li Y, Do R, Walz S, Fitzgerald KN, et al. MYC Regulates the anti-Tumor immune response through CD47 and PD-L1. Science 2016; 352(6282): 227-31. 11. Simonian NA, Coyle JT. Oxidative stress in neurodegenerative diseases. Annu Rev Pharmacol Toxicol 1996; 36: 83-106. 12. Mudbhary R, Sadler KC. Epigenetics, development, and cancer: zebrafish make their mark. Birth Defects Res C Embryo Today 2011; 93(2): 194-203. 13. Westerfield M. The Zebrafish Book, A Guide for the Laboratory Use of Zebrafish. University of Oregon Press, Oregon, USA (1995). 14. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193(1): 265-75. 15. Yagi K. Assay for blood plasma or serum. Methods Enzymol 1981; 105: 328-37. 16. Mylorie AA, Collins H, Umbles C, Kyle J. Erythrocyte SOD activity and other parameters of copper status in rats ingesting lead acetate. Toxicol Appl Pharmacol 1986; 82(3): 512-20. 17. Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 2001; 5(1): 62-71. 18. Hui SP, Sengupta D, Lee SGP, Sen T, Kundu S, Mathavan S. Genome Wide Expression Profiling during Spinal Cord Regeneration Identifies Comprehensive Cellular Responses in Zebrafish. PLoS One 2014; 9(1): e84212. 19. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25(4): 402-8. 20. Diamanti-Kandarakis E, Bourguignon J, Giudice LC, Hauser R, Prins GS, Soto AM, et al. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev 2009; 30(4): 293-342. 21. Gassman NR. Induction of oxidative stress by bisphenol A and its pleiotropic effects. Environ Mol Mutagen 2017; 58(2): 60-71. 22. Liou GY, Storz P. Reactive oxygen species in cancer. Free Radic Res 2010; 44(5): 479-96. 23. Chepelev NL, Enikanolaiye MI, Chepelev LL, Almohaisen A, Chen Q, Scoggan KA, et al. Bisphenol A activates the Nrf1/2-antioxidant response element pathway in HEK 293 cells. Chem Res Toxicol 2013; 26(3): 498-506. 24. Ponniah M, Billett EE, De Girolamo LA. Bisphenol A increases BeWo trophoblast survival in stress-induced paradigms through regulation of oxidative stress and apoptosis. Chem Res Toxicol 2015; 28(9): 1693-703. 25. Erkekoglu P, Giray BK, Kizilgun M, Rachidi W, Hininger-Favier I, Roussel AM, et al. Di(2-ethylhexyl)phthalate-induced renal oxidative stress in rats and protective effect of selenium. Toxicol Mech Methods 2012; 22(6): 415-23. 26. Kuan YH, Huang FM, Li YC, Chang YC. Proinflammatory activation of macrophages by bisphenol A-glycidyl-methacrylate involved NFκB activation via PI3K/Akt pathway. Food Chem Toxicol 2012; 50(11): 4003-9. 27. Pfeifer D, Chung YM, Hu MC. Efects of low-dose bisphenol A on DNA damage and proliferation of breast cells: the role of c-Myc. Environ Health Perspect 2015; 123(12): 1271-9. 28. Benassi B, Fanciulli M, Fiorentino F, Porrello A, Chiorino G, Loda M, et al. c-Myc phosphorylation is required for cellular response to oxidative stress. Mol Cell 2006; 21(4): 509-19.