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Protectivein vivo effect of curcumin on copper genotoxicity evaluated by comet and micronucleus assays

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Abstract

Curcumin is a phytochemical with antiinflammatory, antioxidant and anticarcinogenic activities. Apparently, curcumin is not genotoxicin vivo, butin vitro copper and curcumin interactions induce genetic damage. The aim of this study was to test ifin vivo copper excess induces DNA damage measured by comet and micronucleus assays in the presence of curcumin. We tested 0.2% curcumin in Balb-C mice at normal (13 ppm) and high (65, 130 and 390 ppm) copper ion concentrations. The comet and micronucleus assays were performed 48 hr after chemical application. Comet tail length in animals treated with 0.2% curcumin was not significantly different from the control. Animals exposed to copper cations (up to 390 ppm) exhibited higher oxidative DNA damage. Curcumin reduced the DNA damage induced by 390 ppm copper. We observed statistically significant increase in damage in individuals exposed to 390 ppm copper versus the control or curcumin groups, which was lowered by the presence of curcumin. Qualitative data on comets evidenced that cells from individuals exposed to 390 ppm copper had longer tails (categories 3 and 4) than in 390 ppm copper + curcumin. A statistically significant increase in frequency of micronucleated erythrocytes (MNE/10000TE) was observed only in 390 ppm copper versus the control and curcumin alone. Also cytotoxicity measured as the frequency of polychromatic erythrocytes (PE/1000TE) was attributable to 390 ppm copper. The lowest cytotoxic effect observed was attributed to curcumin.In vivo exposure to 0.2% curcumin for 48 hr did not cause genomic damage, while 390 ppm copper was genotoxic, but DNA damage induced by 390 ppm copper was diminished by curcumin. Curcumin seems to exert a genoprotective effect against DNA damage induced by high concentrations of copper cations. The comet and micronucleus assays prove to be suitable tools to detect DNA damage by copper in the presence of curcumin.

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References

  • Ahsan H, Hadi SM, 1998. Strand scission in DNA induced by curcumin in the presence of Cu(II). Cancer Lett 124: 23–30.

    Article  CAS  PubMed  Google Scholar 

  • Ahsan H, Parveen N, Khan NU, Hadi SM, 1999. Pro-oxidant, anti-oxidant and cleavage activities on DNA of curcumin and its derivatives demethoxycurcumin and bisdemethoxycurcumin. Chem Biol Interact 121: 161–175.

    Article  CAS  PubMed  Google Scholar 

  • Andrighetti-Fröhner CR, Kratz JM, Antonio RV, Creczynski-Pasa TB, Barardi CRM, Simoes CMO, 2006. In vitro testing for genotoxicity of violacein assessed by comet and micronucleus assays. Mutat Res 603: 97–103.

    PubMed  Google Scholar 

  • Antunes LMG, Araújo MCP, Dias FL, Takahashi CS, 1999. Modulatory effects of curcumin on the chromosomal damage induced by doxorubicin in Chinese hamsterovary cells. Teratogen CarcinMut 19: 1–8.

    Article  CAS  Google Scholar 

  • Araujo MCP, Días FL, Takahashi CS, 1999. Potentiation by turmeric and curcumin of -radiation-induced chromosome aberration ien Chinese hamster ovary cells. Teratogen Carcin Mut 19: 9–18.

    Article  CAS  Google Scholar 

  • Araujo CAC, León LL, 2001. Biological activities ofCurcuma longa L. Mem. Inst. Oswaldo Cruz, Río de Janeiro 96: 723–728.

    CAS  Google Scholar 

  • Avishai N, Rabinowitz C, Rinkevick B, 2003. Use of the comet assay for studying environmental genotoxicity. Environ Molec Mutagen 42: 155–165.

    Article  CAS  Google Scholar 

  • Barik A, Mishra B, Shen L, Mohan H, Kadam RM, Dutta S, et al. 2005. Evaluation of a new copper (II)-curcumin complex as superoxide dismutase mimic and free radical reactions. Free Radic Biol Med 39: 811–822.

    Article  CAS  PubMed  Google Scholar 

  • Baum L, Ng A, 2004. Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer’s disease animal models. J Alzheimer’s Dis 6: 367–377; discussion 443–449.

    CAS  Google Scholar 

  • Belpaeme K, Cooreman K, Kirsch-Volders M, 1998. Development and validation of the in vivo alkaline comet assay for detecting genomic damage in marine flatfish. Mutat Res 415: 167–184.

    CAS  PubMed  Google Scholar 

  • Blasiak J, Trzeciak A, Malecka- Panas E, Drzewoski J, Iwanienko T, Szumiel WM, Wojewodzka M, 1999a. DNA damage and repair in human lymphocytes and gastric mucosa cells exposed to chromium and curcumin. Teratogen Carcin Mut 19: 19–31.

    Article  CAS  Google Scholar 

  • Blasiak J, Trzeciak A, Kowalik J, 1999b. Curcumin damages DNA in human gastric mucosa cells and lymphocytes. J Environ Pathol Toxicol Oncol 18: 271–276.

    CAS  PubMed  Google Scholar 

  • Collins AR, 2004. The comet assay for DNA damage and repair principles, applications, and limitations. Mol Biotechnol 26: 249–261.

    Article  CAS  PubMed  Google Scholar 

  • Conney AH, 2003. Enzyme induction and dietary chemical as approaches to cancer. Chemoprevention: 7th De Witt S. Goodman Lecture. Cancer Res: 7005–7031.

  • Eigner D, Scholz D, 1999.Ferula asa-foetida andCurcuma longa in traditional medical treatment and diet in Nepal. J Ethnopharm 67: 1–6.

    Article  CAS  Google Scholar 

  • el Hamss R, Analla M, Campos-Sanchez J, Alonso-Moraga A, Munoz-Serrano A, Idaomar M, 1999. A dose-dependent anti-genotoxic effect of turmeric. Mutat Res 446: 135–139.

    PubMed  Google Scholar 

  • Gaetke LM, Chow CK, 2003. Copper toxicity, oxidative stress, and antioxidant nutrients. Toxicol 189: 147–163.

    Article  CAS  Google Scholar 

  • Hayashi M, Kuge T, Endoh D, Nakayama K, Arihawa J, Tahazawa A, Okuit T, 2000. Hepatic Cu accumulation induces DNA strand breaks in the liver cells of Long-Evans Cinnamon strain rats. Biochem Biophys Res Commun 276: 174–178.

    Article  CAS  PubMed  Google Scholar 

  • Iqbal M, Sharma SD, Okazaki Y, Fujisawa M, Okada S, 2003. Dietary supplementation of curcumin enhances antioxidant and phase II metabolizing enzymes in ddY male mice: Possible role in protection against chemical carcinogenesis and toxicity. Pharmacol Toxicol 92: 33–38.

    Article  CAS  PubMed  Google Scholar 

  • Kawamori T, Lubet R, Steele VE, Kelloff GJ, Kashey RB, Rao CV, 1999. Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent during the promotion/progression stages of colon cancer. Cancer Res 59: 597–601.

    CAS  PubMed  Google Scholar 

  • Kelly MR, Xu J, Alexander KE, Loo G, 2001. Disparate effects of similar phenolic phytochemicals as inhibitors of oxidative damage to cellular DNA. Mutat Res 485: 309–318.

    CAS  PubMed  Google Scholar 

  • Moraes de Andrade V, da Silva J, da Silva FR, Heuser VD, Dias JF, Yoneama ML, de Freitas TRO, 2004. Fish as bioindicators to assess the effects of pollution in two southern Brazilian rivers using the comet assay and micronucleus test. Environ Molec Mutagen 44: 000–000?.

    CAS  Google Scholar 

  • Mukhopadhyay MJ, Mukherjee SA. 1998. Studies on the antic lastogenic effect of turmeric and curcumin on cyclophosphamide and mitomycin Cin vivo. Food Chem Toxicol 36: 73–76.

    Article  CAS  PubMed  Google Scholar 

  • Murray MT, Pizzorno JE, 1999.Curcuma longa (turmeric). In: Textbook of Natural Medicine. Churchill Livingstone, Inc.: 689.

  • Nair J, Strand S, Frank N, Knauft J, Wesch H, Galee PR, Bartsch H, 2005. Apoptosis and age-dependant induction of nuclear and mitochondrial etheno-DNA adducts in Long-Evans Cinnamon (LEC) rats: enhanced DNA damage by dietary curcumin upon copper accumulation. Carcinogenesis 26: 1307–1315.

    Article  CAS  PubMed  Google Scholar 

  • Polasa K, Naidu AN, Ravindranath I, Krishnaswamy K, 2004. Inhibition of B(a)P-induced strand breaks in presence of curcumin. Mut Res 557: 203–213.

    CAS  Google Scholar 

  • Rao CV, Kawamori T, Hamid R, Reddy BS, 1999. Chemoprevention of colonic aberrant crypt foci by an inducible nitric oxide synthase-selective inhibitor. Carcinogenesis 20: 641–644.

    Article  CAS  PubMed  Google Scholar 

  • Saleha Banu B, Ishaq M, Danadevi K, Padmavathi P, Ahuja RY, 2004. DNA in leukocytes of mice treated with Cu sulfate. Food Chem Toxicol 42: 1931–1936.

    Article  Google Scholar 

  • Shukla Y, Arora A, Taneja P, 2003. Antigenotoxic potential of certain dietary constituents. Teratogen Carcin Mut 23 Suppl 1: 323–335.

    Article  Google Scholar 

  • Singh NP, McCoy MT, Tice RR, Schneider EL, 1988. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175: 184–191.

    Article  CAS  PubMed  Google Scholar 

  • Sugiyama Y, Kawakishi S, Osawa T, 1996. Involvement of the beta-diketone moiety in the anti-oxidative mechanism of tetrahydrocurcumin. Biochem Pharmacol 52: 519–525.

    Article  CAS  PubMed  Google Scholar 

  • Urbina-Cano P, Bobadilla-Morales L, Ramírez-Herrera MA, Corona-Rivera JR, Mendoza- MagańaML, Troyo-Sanromán R, Corona- Rivera A, 2006. DNA damage in mouse lymphocytes exposed to curcumin and copper. J Appl Genet 47: 377–382.

    Article  PubMed  Google Scholar 

  • Vijayalaxmi, 1980. Genetic effects of turmeric and curcumin in mice and rats. Mutat Res 79: 125–132.

    Article  CAS  PubMed  Google Scholar 

  • Yoshino M, Haneda M, Naruse M, Htay HH, Tsubouchi R, Qiao SL, et al. 2004. Prooxidant activity of curcumin: copper-dependent formation of 8-hydroxy-2’-deoxyguanosine in DNA and induction of apoptotic cell death. Toxicology in vitro 18: 783–789.

    Article  CAS  PubMed  Google Scholar 

  • Zhong Y, Feng SL, Luo Y, Zhang GD, Kong ZM, 2001. Evaluating the genotoxicity of surface water of Yangzhong city using theVicia faba micronucleus test and the comet Assay. Bull Environ Contam Toxicol 67: 217–224.

    CAS  PubMed  Google Scholar 

  • Zuñiga-González G, Torres-Bugarín O, Luna-Aguirre J, González-Rodriguez A, Zamora-Pérez A, Gómez-Meda BC, et al. 2000. Spontaneous micronuclei in peripheral blood erythrocytes from 54 animal species (mammals, reptiles and birds): Part 2. Mutat Res 467: 99–103.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Departamento de Biología Molecular y Genómica, Instituto de Genética Humana “Dr. Enrique Corona Rivera”, Laboratorio de Citogenética Genotoxicidad y Biomonitoreo, Universidad de Guadalajara, Centro Universitario de Ciencias de la Salud, Edificio P, 2do Nivel, Sierra Mojada # 950, Colonia Independencia, S.L., CP-44340, Guadalajara, Jalisco, México

    Alfredo Corona-Rivera, Patricia Urbina-Cano, Lucina Bobadilla-Morales, José de Jesús Vargas-Lares, Rogelio Troyo-Sanromán & Jorge Román Corona-Rivera

  2. Laboratorio de Neurofisiología, Departamento de Fisiología, Universidad de Guadalajara, Jalisco, México

    Mario Alberto Ramírez-Herrera & María Luisa Mendoza-Magaña

  3. Bioterio, Coordinación de Investigación, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México

    Pedro Díaz-Esquivel

  4. Laboratorio de Citogenética, OPD, Hospitales Civiles de Guadalajara, Guadalajara, Jalisco, México

    Alfredo Corona-Rivera & Jorge Román Corona-Rivera

Authors
  1. Alfredo Corona-Rivera
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  2. Patricia Urbina-Cano
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  3. Lucina Bobadilla-Morales
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  4. José de Jesús Vargas-Lares
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  5. Mario Alberto Ramírez-Herrera
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  6. María Luisa Mendoza-Magaña
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  7. Rogelio Troyo-Sanromán
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  8. Pedro Díaz-Esquivel
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  9. Jorge Román Corona-Rivera
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Correspondence to Alfredo Corona-Rivera.

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Corona-Rivera, A., Urbina-Cano, P., Bobadilla-Morales, L. et al. Protectivein vivo effect of curcumin on copper genotoxicity evaluated by comet and micronucleus assays. J Appl Genet 48, 389–396 (2007). https://doi.org/10.1007/BF03195238

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  • DOI: https://doi.org/10.1007/BF03195238

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