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Journal of Basic and Clinical Physiology and Pharmacology

Editor-in-Chief: Horowitz, Michal

Editorial Board: Das, Kusal K. / Epstein, Yoram / S. Gershon MD, Elliot / Kodesh , Einat / Kohen, Ron / Lichtstein, David / Maloyan, Alina / Mechoulam, Raphael / Roth, Joachim / Schneider, Suzanne / Shohami, Esther / Sohmer, Haim / Yoshikawa, Toshikazu / Tam, Joseph

CiteScore 2016: 1.01

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Volume 30, Issue 3


Assessment of epigenetic changes and oxidative DNA damage in rat pups exposed to polychlorinated biphenyls and the protective effect of curcumin in the prenatal period

Halef Okan Doğan
  • Corresponding author
  • Department of Biochemistry, Faculty of Medicine, University of Cumhuriyet, Sivas, Turkey
  • Director of Laboratory Animals Research Center, Faculty of Medicine, University of Cumhuriyet, Sivas, Turkey, Phone: +903462191010/1377
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mehmet Eray Alçiğir
  • Kırıkkale University, Department of Pathology, Faculty of Veterinary, Kırıkkale, Turkey
  • Department of Pathology, Faculty of Medicine, University of Ankara, Ankara, Turkey
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2019-03-27 | DOI: https://doi.org/10.1515/jbcpp-2018-0182



Polychlorinated biphenyls (PCBs) are persistent organic chemicals that exert neurotoxic and endocrine disrupting effects. The aims of this study were to examine the effects of prenatal Aroclor 1254 (PCBs mixture) exposure on central nervous system tissues DNA and to evaluate the effects of curcumin.


Rat pups were assigned to three groups: [Group 1], Aroclor 1254 administrated group; [Group 2], Aroclor 1254 and curcumin administrated group; and [Group 3], control group. Plasma, cerebrum, cerebellum, pons and medulla oblongata tissue homogenates 8-hydroxy-2′-deoxyguanosine [8-(OH)DG] levels and plasma freeT4 levels were determined. Global DNA methylation and hydroxymethylation status were determined in cerebrum, cerebellum, pons and medulla oblongata. To this aim, DNA 5-hydroxymethylcytosine and 5-methylcytosine levels were measured, respectively.


Mean cerebellum and cerebral cortex 5-hydroxymethylcytosine and 5-methylcytosine levels were higher in the control group than in the experimental groups. Mean plasma, cerebellum and cerebral cortex 8-(OH)DG concentrations were higher in Group 1 than the control group. No statistically significant difference was observed between Group 2 and the control group in terms of cerebellum and cerebral cortex 8-(OH)DG concentrations. Histopathological changes were also observed in the cerebral cortex and cerebellum of rat pups exposed to Aroclor 1254. PCBs exposure changes both DNA methylation and hypomethylation status and induces cerebellar and cerebral cortex DNA damage in the prenatal period. Exogenous curcumin may have protective effect on PCBs-induced DNA damage in cerebellum and cerebral cortex.

Keywords: curcumin; developmental neurotoxicity; DNA damage; 5-hydroxymethylcytosine; 5-methylcytosine; polychlorinated biphenyl


  • [1]

    Pariatamby A, Kee YL. Persistent organic pollutants management and remediation. Procedia Environ Sci 2016;31:842–8.CrossrefGoogle Scholar

  • [2]

    Ward MH, Colt JS, Metayer C, Gunier RB, Lubin J, Crouse V, et al. Residential exposure to polychlorinated biphenyls and organochlorine pesticides and risk of childhood leukemia. Environ Health Perspect 2009;117:1007–13.CrossrefPubMedWeb of ScienceGoogle Scholar

  • [3]

    Schantz SL, Widholm JJ, Rice DC. Effects of PCB exposure on neuropsychological function in children. Environ Health Perspect 2003;111:357–76.PubMedCrossrefGoogle Scholar

  • [4]

    Aliyu MH, Alio AP, Salihu HM. To breastfeed or not to breastfeed: a review of the impact of lactational exposure to polychlorinated biphenyls (PCBs) on infants. J Env Heal 2010;73:8–14.Google Scholar

  • [5]

    Landrigan PJ, Sonawane B, Mattison D, McCally M, Garg A. Chemical contaminants in breast milk and their impacts on children’s health: an overview. Environ Health Perspect 2002;110:313–5.Google Scholar

  • [6]

    van den Berg M, Kypke K, Kotz A, Tritscher A, Lee SY, Magulova K, et al. WHO/UNEP global surveys of PCDDs, PCDFs, PCBs and DDTs in human milk and benefit-risk evaluation of breastfeeding. Arch Toxicol 2017;91:83–96.Web of ScienceCrossrefPubMedGoogle Scholar

  • [7]

    Ribas-Fitó N, Sala M, Kogevinas M, Sunyer J. Polychlorinated biphenyls (PCBs) and neurological development in children: a systematic review. J Epidemiol Community Health 2001;55:537–46.CrossrefPubMedGoogle Scholar

  • [8]

    Choksi NY, Kodavanti PR, Tilson HA, Booth RG. Effects of polychlorinated biphenyls (PCBs) on brain tyrosine hydroxylase activity and dopamine synthesis in rats. Toxicol Sci 1997;39:76–80.CrossrefGoogle Scholar

  • [9]

    Gauger KJ, Kato Y, Haraguchi K, Lehmler HJ, Robertson RW, Bansal R, et al. Polychlorinated biphenyls (PCBs) exert thyroid hormone-like effects in the fetal rat brain but do not bind to thyroid hormone receptors. Environ Health Perspect 2004;112:516–23.CrossrefPubMedGoogle Scholar

  • [10]

    Lee DW, Opanashuk LA. Polychlorinated biphenyl mixture aroclor 1254-induced oxidative stress plays a role in dopaminergic cell injury. Neurotoxicology 2004;25:925–39.CrossrefGoogle Scholar

  • [11]

    Ock CY, Kim EH, Choi DJ, Lee HJ, Hahm KB, Chung MH. 8-hydroxydeoxyguanosine: not mere biomarker for oxidative stress, but remedy for oxidative stress-implicated gastrointestinal diseases. World J Gastroenterol 2012;18:302–8.CrossrefPubMedGoogle Scholar

  • [12]

    Valavanidis A, Vlachogianni T, Fiotakis C. 8-hydroxy-2′-deoxyguanosine (8-OHdG): a critical biomarker of oxidative stress and carcinogenesis. J Environ Sci Health C 2009;27:120–39.Web of ScienceCrossrefGoogle Scholar

  • [13]

    Li R, Cao S, Dai J, Wang L, Li L, Wang Y, et al. Effect of caffeic acid derivatives on polychlorinated biphenyls induced hepatotoxicity in male mice. J Biomed Res 2014;28:423–8.PubMedGoogle Scholar

  • [14]

    Wen S, Yang F-X, Gong Y, Zhang X-L, Hui Y, Li J-G, et al. Elevated levels of urinary 8-hydroxy-2′-deoxyguanosine in male electrical and electronic equipment dismantling workers exposed to high concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans, polybrominated diphenyl ethers, and polychlorinat. Environ Sci Technol 2008;42:4202–7.PubMedCrossrefGoogle Scholar

  • [15]

    Urdinguio RG, Sanchez-Mut JV, Esteller M. Epigenetic mechanisms in neurological diseases: genes, syndromes, and therapies. Lancet Neurol 2009;8:1056–72.CrossrefWeb of SciencePubMedGoogle Scholar

  • [16]

    Hou L, Zhang X, Wang D, Baccarelli A. Environmental chemical exposures and human epigenetics. Int J Epidemiol 2012;41:79–105.Web of ScienceCrossrefPubMedGoogle Scholar

  • [17]

    Lian CG, Xu Y, Ceol C, Wu F, Larson A, Dresser K, et al. Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma. Cell 2012;150:1135–46.CrossrefWeb of SciencePubMedGoogle Scholar

  • [18]

    Casati L, Sendra R, Poletti A, Negri-Cesi P, Celotti F. Androgen receptor activation by polychlorinated biphenyls. Epigenetics 2013;8:1061–8.CrossrefPubMedGoogle Scholar

  • [19]

    Desaulniers D, Xiao G, Lian H, Feng Y-L, Zhu J, Nakai J, et al. Effects of mixtures of polychlorinated biphenyls, methylmercury, and organochlorine pesticides on hepatic DNA methylation in prepubertal female Sprague-Dawley rats. Int J Toxicol 2009;28:294–307.PubMedCrossrefWeb of ScienceGoogle Scholar

  • [20]

    Chongtham A, Agrawal N. Curcumin modulates cell death and is protective in Huntington’s disease model. Sci Rep 2016;6:18736.PubMedWeb of ScienceGoogle Scholar

  • [21]

    Gazal M, Valente MR, Acosta BA, Kaufmann FN, Braganhol E, Lencina CL, et al. Neuroprotective and antioxidant effects of curcumin in a ketamine-induced model of mania in rats. Eur J Pharmacol 2014;724:132–9.Web of ScienceCrossrefGoogle Scholar

  • [22]

    Zhao J, Zhao Y, Zheng W, Lu Y, Feng G, Yu S. Neuroprotective effect of curcumin on transient focal cerebral ischemia in rats. Brain Res 2008;1229:224–32.PubMedWeb of ScienceCrossrefGoogle Scholar

  • [23]

    Reuter S, Gupta SC, Park B, Goel A, Aggarwal BB. Epigenetic changes induced by curcumin and other natural compounds. Genes Nutr 2011;6:93–108.Web of SciencePubMedCrossrefGoogle Scholar

  • [24]

    Rice D, Barone S. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect 2000;108(Suppl 3):511–33.PubMedGoogle Scholar

  • [25]

    Selvakumar K, Bavithra S, Krishnamoorthy G, Venkataraman P, Arunakaran J. Polychlorinated biphenyls-induced oxidative stress on rat hippocampus: a neuroprotective role of quercetin. Sci World J 2012;2012:980314.Web of ScienceGoogle Scholar

  • [26]

    Venkataraman P, Krishnamoorthy G, Selvakumar K, Arunakaran J. Oxidative stress alters creatine kinase system in serum and brain regions of polychlorinated biphenyl (Aroclor 1254)-exposed rats: protective role of melatonin. Basic Clin Pharmacol Toxicol 2009;105:92–7.PubMedWeb of ScienceCrossrefGoogle Scholar

  • [27]

    Venkataraman P, Muthuvel R, Krishnamoorthy G, Arunkumar A, Sridhar M, Srinivasan N, et al. PCB (Aroclor 1254) enhances oxidative damage in rat brain regions: protective role of ascorbic acid. Neurotoxicology 2007;28:490–8.CrossrefPubMedWeb of ScienceGoogle Scholar

  • [28]

    Kimura-Kuroda J, Nagata I, Kuroda Y. Disrupting effects of hydroxy-polychlorinated biphenyl (PCB) congeners on neuronal development of cerebellar Purkinje cells: a possible causal factor for developmental brain disorders? Chemosphere 2007;67:412–20.CrossrefWeb of ScienceGoogle Scholar

  • [29]

    ASTDR. Toxicological profile for polychlorinated biphenyls (PCBs). Agency Toxic Subst Dis Regist 2000;1–948.Google Scholar

  • [30]

    Roegge CS, Morris JR, Villareal S, Wang VC, Powers BE, Klintsova AY, et al. Purkinje cell and cerebellar effects following developmental exposure to PCBs and/or MeHg. Neurotoxicol Teratol 2006;28:74–85.PubMedCrossrefGoogle Scholar

  • [31]

    Ahmed RG. Early weaning PCB 95 exposure alters the neonatal endocrine system: thyroid adipokine dysfunction. J Endocrinol 2013;219:205–15.PubMedWeb of ScienceCrossrefGoogle Scholar

  • [32]

    Ahmed RG, El-Gareib AW, Shaker HM. Gestational 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) exposure disrupts fetoplacental unit: fetal thyroid-cytokines dysfunction. Life Sci 2018;192:213–20.Web of SciencePubMedCrossrefGoogle Scholar

  • [33]

    Longnecker MP, Gladen BC, Patterson DG Jr, Rogan WJ. Polychlorinated biphenyl (PCB) exposure in relation to thyroid hormone levels in neonates. Epidemiology 2000;11:249–54.CrossrefPubMedGoogle Scholar

  • [34]

    Osius N, Karmaus W, Kruse H, Witten J. Exposure to polychlorinated biphenyls and levels of thyroid hormones in children. Children’s Health 1999;107:843–9.Google Scholar

  • [35]

    Chan W, Wu H. Protective effects of curcumin on methylglyoxal-induced oxidative DNA damage and cell injury in human mononuclear cells. Acta Pharmacol Sin 2006;27:1192–8.CrossrefPubMedGoogle Scholar

  • [36]

    Ciftci G, Aksoy A, Cenesiz S, Sogut MU, Yarim GF, Nisbet C, et al. Therapeutic role of curcumin in oxidative DNA damage caused by formaldehyde. Microsc Res Tech 2015;78:391–5.CrossrefPubMedWeb of ScienceGoogle Scholar

  • [37]

    Ibrahim MA, Elbehairy AM, Ghoneim MA, Amer HA. Protective effect of curcumin and chlorophyllin against DNA mutation induced by cyclophosphamide or benzo[a]pyrene. Zeitschrift fur Naturforsch – Sect C J Biosci. 2007;62:215–22.CrossrefGoogle Scholar

  • [38]

    Rai B, Kaur J, Jacobs R, Singh J. Possible action mechanism for curcumin in pre-cancerous lesions based on serum and salivary markers of oxidative stress. J Oral Sci 2010;52:251–6.CrossrefPubMedGoogle Scholar

  • [39]

    Keil KP, Lein PJ. DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? Environ Epigenetics 2016;2:dvv012.CrossrefWeb of ScienceGoogle Scholar

  • [40]

    Kim K-Y, Kim D-S, Lee S-K, Lee I-K, Kang J-H, Chang Y-S, et al. Association of low-dose exposure to persistent organic pollutants with global DNA hypomethylation in healthy Koreans. Environ Health Perspect 2009;118:370–4.Web of SciencePubMedGoogle Scholar

  • [41]

    Itoh H, Iwasaki M, Kasuga Y, Yokoyama S, Onuma H, Nishimura H, et al. Association between serum organochlorines and global methylation level of leukocyte DNA among Japanese women: a cross-sectional study. Sci Total Environ 2014;490:603–9.Web of SciencePubMedCrossrefGoogle Scholar

  • [42]

    Tellez-Plaza M, Tang W, Shang Y, Umans JG, Francesconi KA, Goessler W, et al. Association of global DNA methylation and global DNA hydroxymethylation with metals and other exposures in human blood DNA samples. Environ Health Perspect 2014;122:946–54.Web of SciencePubMedGoogle Scholar

  • [43]

    Li Y, Liu L, Andrews LG, Tollefsbol TO. Genistein depletes telomerase activity through cross-talk between genetic and epigenetic mechanisms. Int J Cancer 2009;125:286–96.Web of ScienceCrossrefPubMedGoogle Scholar

  • [44]

    Medina-Franco JL, López-Vallejo F, Kuck D, Lyko F. Natural products as DNA methyltransferase inhibitors: a computer-aided discovery approach. Mol Divers 2011;15:293–304.Web of ScienceCrossrefPubMedGoogle Scholar

About the article

Received: 2018-10-05

Accepted: 2018-11-22

Published Online: 2019-03-27

Funding Source: Cumhuriyet University

Award identifier / Grant number: T-659

Financial support was provided by Cumhuriyet University Scientific Research Department (Funder Id: 10.13039/501100002966, T-659).

Author contribution: HOD: Study design, biochemical analysis, interpretation of the results and writing manuscript; EA: Pathologic analysis, interpretation of the results.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interest: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Journal of Basic and Clinical Physiology and Pharmacology, Volume 30, Issue 3, 20180182, ISSN (Online) 2191-0286, DOI: https://doi.org/10.1515/jbcpp-2018-0182.

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