Importance of the copper/zinc ratio: an approach to the analysis of the effect of in vitro copper/zinc supplementation on the genome
DOI:
https://doi.org/10.24215/18536387e052Keywords:
micronutrients, peripherical blood, DNA damageAbstract
Copper (Cu) and zinc (Zn) are essential micronutrients that are involved in numerous metabolic activities. The Cu/Zn ratio is even more important than individual micronutrient concentrations, and is one of the parameters associated with the reduction of homeostasis during a stressful event. Since micronutrient deficiency and excess are not detected by anthropometric techniques, it is necessary to design experimental models to investigate the effects of these micronutrients and provide information for the implementation of health prevention policies. Taking into account the Cu/Zn ratio, the objective of this work was to analyze the effect of combined Cu and Zn supplementation on genomic stability in peripheral blood cultured in vitro. Cells were cultured for five days. Eight treatments were implemented: three combinations with zinc sulfate (SO4Zn), copper sulfate (SO4Cu), and their respective controls. The comet assay was used to assess DNA damage and the damage index (DI) was determined. ANOVA and Fisher’s LSD method were used for statistical analysis. Significantly higher DI frequencies were observed as the Cu/Zn ratio increased. Considering that Cu and Zn play a fundamental role in maintaining genomic stability, and also in child growth, disease development, and aging, we recommend that adequate Cu and Zn daily intakes should be determined.
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Aguirre, P. (2005). Contribución para el diseño de una política alimentaria. Centro interdisciplinario para el estudio de las políticas públicas (CIEPP).
Aguirre, P. (2010). La comida en los tiempos del ajuste. En S. Torrado (dir.), El costo social del ajuste (Argentina 1976-2002). Tomo II (pp. 51-102). Buenos Aires: Edhasa.
Aksu, B Y, Hasbal, C, Himmetoglu, S, Dincer, Y, Koc, E E, Hatipoglu, S, y Akcay, T (2010). Leukocyte DNA damage in children with iron deficiency anemia: effect of iron supplementation. European Journal of Pediatrics, 169(8), 951-956. https://doi.org/10.1007/s00431-010-1147-1
Ambrosone, C. B., Freudenheim, J. L., Thompson, P. A., Bowman, E., Vena, J. E., Marshall, J. R., y Shields, P. G. (1999). Manganese superoxide dismutase (MnSOD) genetic polymorphisms, dietary antioxidants, and risk of breast cancer. Cancer research, 59(3), 602-606
Antwi-Boasiako, C., Dankwah, G. B., Aryee, R., Hayfron-Benjamin, C., Doku, A., N’guessan, B. B., y Campbell, A. D. (2019). Serum iron levels and copper-to-zinc ratio in sickle cell disease. Medicina, 55(5), 180. https://doi.org/10.3390/medicina55050180
Bergel Sanchís, M. L., Cesani, M. F. y Oyhenart, E.E. (2017). Malnutrición infantil e inseguridad alimentaria como expresión de las condiciones socio-económicas familiares en Villaguay, Argentina (2010-2012). Un enfoque biocultural. Población y Salud en Mesoamérica, 14(2), 60-85. https://doi.org/10.15517/psm.v14i2.27305
Böckerman, P., Bryson, A., Viinikainen, J., Viikari, J., Lehtimäki, T., Vuori, E., y Pehkonen, J. (2016). The serum copper/zinc ratio in childhood and educational attainment: a population-based study. Journal of Public Health, 38(4), 696-703. https://doi.org/10.1093/pubmed/fdv187
Borrás, G. y García, J. (2013). Políticas alimentarias en Argentina, derechos y ciudadanía. Revista Interdisciplinaria de Estudios Agrarios, 39, 111-136.
Carmuega, E. (1999). La calidad de la dieta de los dos primeros años de vida. En: A. O´Donnell y E.
Carmuega. Hoy y Mañana. Salud y calidad de vida de la Niñez Argentina. Buenos Aires: CESNI.
Carrero, C., Leal, J., Mavo, L., Parody, A., Granadillo, V., y Fernández, D. (2016). Retinol y zinc séricos en escolares sometidos a suplementación nutricional de la Escuela Bolivariana” Catatumbo”, Maracaibo, Estado Zulia. Revista Científica General José María Córdova, 14(18), 324-332. http://www.redalyc.org/articulo.oa?id=476255360015
Collins, A. (2004). The comet assay for DNA damage repair: principles, applications, and limitations. Mol. Biotechnol, 26(3), 249-261. https://doi.org/10.1385/MB:26:3:249
Demonte, F. C. (2016) Un análisis de las políticas sociales alimentarias en la Argentina reciente (2001-2008). Población & Sociedad, 23(1), 5-43. http://sedici.unlp.edu.ar/handle/10915/108057
Eom, S. Y., Yim, D. H., Huang, M., Park, C. H., Kim, G. B., Yu, S. D., y Kim, H. (2020). Copper–zinc imbalance induces kidney tubule damage and oxidative stress in a population exposed to chronic environmentalcadmium. International archives of occupational and environmental health, 93(3), 337-344. https://doi.org/10.1007/s00420-019-01490-9
Escobedo-Monge, M. F., Barrado, E., Alonso Vicente, C., Escobedo-Monge, M. A., Torres-Hinojal, M.C., Marugán-Miguelsanz, J. M., y Redondo del Río, M. P. (2020). Copper and Copper/Zinc Ratio in a Series of Cystic Fibrosis Patients. Nutrients, 12(11), 3344. https://doi.org/10.3390/nu12113344
Fedor, M., Socha, K., Urban, B., Soroczyńska, J., Matyskiela, M., Borawska, M. H., y BakunowiczŁazarczyk, A. (2017). Serum concentration of zinc, copper, selenium, manganese, and Cu/Zn ratio in children and adolescents with myopia. Biological trace element research, 176(1), 1-9. https://doi.org/10.1007/s12011-016-0805-1
Feliu, M. S., Piñeiro, A., López, C., y Slobodianik, N. H. (2005). Valores de referencia de cobre, zinc y selenio en niños. Acta bioquímica clínica latinoamericana, 39(4), 459-462. http://www.redalyc.org/articulo.oa?id=53539407
Fenech, M. (2001). Recommended dietary allowances (RDAs) for genomic stability. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 480, 51-54. https://doi.org/10.1016/S0027-5107(01)00168-3
Fenech, M. (2005). The Genome Health Clinic and Genome Health Nutrigenomics concepts: diagnosis and nutritional treatment of genome and epigenome damage on an individual basis. Mutagenesis, 20(4), 255-269. https://doi.org/10.1093/mutage/gei040
Fenech, M. (2010). Dietary reference values of individual micronutrients and nutriomes for genome damage prevention: current status and a road map to the future. The American journal of clinical nutrition, 91(5), 1438S-1454S. https://doi.org/10.3945/ajcn.2010.28674D
Fenech, M. (2014). Nutriomes and personalised nutrition for DNA damage prevention, telomere integrity maintenance and cancer growth control. Advances in nutrition and cancer, 427-441. https://doi.org/10.1007/978-3-642-38007-5_24
Fraga, C G, y Oteiza, P I (2002). Iron toxicity and antioxidant nutrients. Toxicology, 180(1), 23-32. https://doi.org/10.1016/S0300-483X(02)00379-7
Gaetke, L. M., y Chow, C. K. (2003). Copper toxicity, oxidative stress, and antioxidant nutrients. Toxicology, 189(1-2), 147-163. https://doi.org/10.1016/S0300-483X(03)00159-8
Giovannucci, E., Stampfer, M. J., Colditz, G. A., Hunter, D. J., Fuchs, C., Rosner, B. A., y Willett, W. C. (1998). Multivitamin use, folate, and colon cancer in women in the Nurses’ Health Study. Annals of internal medicine, 129(7), 517-524. https://doi.org/10.7326/0003-4819-129-7-199810010-00002
Guevara, D. A., Reyes, S., López, M., Flores, N., Aguirre, S., Muñoz, E. B., Fornasini, M. y Baldeón, M. E. (2017). Impact of milk based micronutrient supplementation in school children in Quito-Ecuador. Nutrición Hospitalaria, 34(6), 1305-1313. https://doi.org/10.20960/nh.1353
Guo, C. H., y Wang, C. L. (2013). Effects of zinc supplementation on plasma copper/zinc ratios, oxidative stress, and immunological status in hemodialysis patients. International journal of medical sciences, 10(1), 79–89. https://doi.org/10.7150/ijms.5291
Haldsrud, R., y Krøkje, A. (2009). Induction of DNA double-strand breaks in the H4IIE cell line exposed to environmentally relevant concentrations of copper, cadmium, and zinc, singly and in combinations. Journal of toxicology and environmental health. Part A, 72(3-4), 155–163. https://doi.org/10.1080/15287390802538964
Jerez M., Carreño M., Castro A., Marino Alarcón Corredor O., Rondon C., García Fernandez M.Y. y Di Bernardo Navas M.L. (2021). Importancia de la relación cobre-zinc como indicador bioquímico de dismenorrea primaria. Red Científica Latinoamericana. https://www.siicsalud.com/acise_viaje/ensiicas-profundo.php?id=123840
Johnson, W. T., y Thomas, A. C. (1999). Copper Deprivation Potentiates Oxidative Stress in HL‐60 Cell Mitochondria. Proceedings of the Society for Experimental Biology and Medicine, 221(2), 147-152. https://doi.org/10.1046/j.1525-1373.1999.d01-68.x
Jomova, K, y Valko, M (2011). Importance of Iron Chelation in Free Radical-Induced Oxidative Stress and Human Disease. Current Pharmaceutical Design. https://www.ingentaconnect.com/content/ben/cpd/2011/00000017/00000031/art00010
Kambe, T., Weaver, B. P., y Andrews, G. K. (2008). The genetics of essential metal homeostasis during development. Genesis, 46(4), 214-228. https://doi.org/10.1002/dvg.20382
Kasprzak, K. (2002) Oxidative DNA damage in metal-induced carcinogenesis. In: Chang LW, editor. Toxicology of Metals. CRC Press Inc, Boca Raton FL, pp. 299–320. https://doi.org/10.1016/s0891-5849(02)00809-2
Kimura, M., Umegaki, K., Higuchi, M., Thomas, P., y Fenech, M. (2004). Methylenetetrahydrofolate reductase C677T polymorphism, folic acid and riboflavin are important determinants of genome stability in cultured human lymphocytes. The Journal of nutrition, 134(1), 48-56. https://doi.org/10.1093/jn/134.1.48
Lin, H, Li, L, Jia, X, Ward, D M, y Kaplan, J (2011). Genetic and Biochemical Analysis of High Iron Toxicity in Yeast. Journal of Biological Chemistry, 286(5), 3851-3862. https://doi.org/10.1074/jbc.M110.190959
Malavolta M., Piacenza F., Basso A., Giacconi R., Costarelli L., y Mocchegiani, E. (2015). Serum copper to zinc ratio: Relationship with aging and health status. Mechanisms of Ageing and Development, 151, 93-100. https://doi.org/10.1016/j.mad.2015.01.004
Maury Sintjago, E., Mattei, A., Perozo, K., Bravo, A., Martínez, E., y Vizcarra, M. (2010). Niveles Plasmáticos de Hierro, Cobre y Zinc en escolares Barí. Pediatría (Asunción), 37(2), 112-117. https://www.revistaspp.org/index.php/pediatria/article/view/204
Mezzetti, A., Pierdomenico, S. D., Costantini, F., Romano, F., De Cesare, D., Cuccurullo, F., y Fellin, R. (1998). Copper/zinc ratio and systemic oxidant load: effect of aging and aging-related degenerative diseases. Free Radical Biology and Medicine, 25(6), 676-681. https://doi.org/10.1016/S0891-5849(98)00109-9
Morris, M. C., Beckett, L. A., Scherr, P. A., Hebert, L., Bennett, D. A., Field, T. S., y Evans, D. A. (1998). Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease. Alzheimer disease and associated disorders 12(3), 121–126. https://doi.org/10.1097/00002093-199809000-00001
Olive, P. (1999) DNA damage and repair in individual cells: applications of the comet assay in radiobiology. Int. J. Radiat. Biol, 75, 395. https://doi.org/10.1080/095530099140311
OMS (2002). The world health report 2002. Reducing risks, promoting healthy life. Ginebra, Suiza. https://apps.who.int/iris/bitstream/handle/10665/42510/WHR_2002.pdf
Osredkar, J., y Sustar, N. (2011). Copper and zinc, biological role and significance of copper/zinc imbalance. J Clinic Toxicol S, 3(2161), 0495. http://dx.doi.org/10.4172/2161-0495.S3-001
Padula, G., Ponzinibbio, M. V., y Seoane, A. I. (2014). Suplementación de cultivos de sangre periférica con sulfato de zinc: inestabilidad genómica asociada a su deficiencia y exceso. BAG. Journal of basic and applied genetics, 25(2), 41-52.
Padula, G., Ponzinibbio, M. V., Gambaro, R. C., y Seoane, A. I. (2017). Genomic instability related to zinc deficiency and excess in an in vitro model: is the upper estimate of the physiological requirements recommended for children safe? In Vitro Cellular & Developmental Biology-Animal, 53(7), 586-592. http://dx.doi.org/10.1007/s11626-017-0146-1
Padula, G., Matella M., Gambaro, R. y Seoane A. I. (2021). Importancia de los micronutrientes en el crecimiento y desarrollo de la población infantil. RUNA, 42(2), 83-97.
Picco S., Padula G., Anchordoquy J.M., Anchordoquy J.P., Furnus C., y Seoane, A (2020). Consequences of copper and zinc co-supplementation on DNA integrity and apoptosis of bovine cumulus cells during oocyte in vitro maturation. Animal Science Papers and Reports, 38(2), 145-153.
Picco, S. J., Abba, M. C., Mattioli, G. A., Fazzio, L. E., Rosa, D., De Luca, J. C., y Dulout, F. N. (2004). Association between copper deficiency and DNA damage in cattle. Mutagenesis, 19(6), 453-456. https://doi.org/10.1093/mutage/geh056
Prá, D, Franke, S I R, Henriques, J A P, y Fenech, M (2012). Iron and genome stability: An update. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 733(1-2), 92-99. https://doi.org/10.1016/j.mrfmmm.2012.02.001
Rahn-Chique, K., Carrión, N., y Murillo, M. (2012). Determinación de cobre, magnesio y zinc en leucocitos mononucleares mediante espectrometría de absorción atómica con llama. Investigación clínica, 53(4), 34Selhub, J., Bagley, L. C., Miller, J., y Rosenberg, I. H. (2000). B vitamins, homocysteine, and neurocognitive function in the elderly. The American journal of clinical nutrition, 71(2), 614S-620S. https://doi.org/10.1093/ajcn/71.2.614s
Sharif, R., Thomas, P., Zalewski, P., Graham, R. D., y Fenech, M. (2011). The effect of zinc sulphate and zinc carnosine on genome stability and cytotoxicity in the WIL2- NS human lymphoblastoid cell line. Mutat. Res., 720, 22-33. https://doi.org/10.1016/j.mrgentox.2010.12.004
Sharif, R., Thomas, P., Zalewski, P., y Fenech, M. (2012). The role of zinc in genomic stability. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 733(1-2), 111-121. https://doi.org/10.1016/j.mrfmmm.2011.08.009
Singh, N. P., McCoy, M. T., Tice, R. R., y Schneider, E. L. (1988). A simple technique for quantitation of lowlevels of DNA damage in individual cells. Experimental cell research, 175(1), 184-191. https://doi.org/10.1016/0014-4827(88)90265-0
Singh, R. P., Kumar, S., Nada, R., y Prasad, R. (2006). Evaluation of copper toxicity in isolated human peripheral blood mononuclear cells and it’s attenuation by zinc: ex vivo. Molecular and cellular biochemistry, 282(1), 13-21. https://doi.org/10.1007/s11010-006-1168-2
Suttle, N.F. (2010). Mineral Nutrition of Livestock. 4th Edition, CABI, Cambridge. http://dx.doi.org/10.1079/9781845934729.0000
Toxqui, L, De Piero, A, Courtois, V, Bastida, S, Sánchez Muniz, F J, y Vaquero, M P (2010). Iron deficiency and overload. Implications in oxidative stress and cardiovascular health. Nutricion Hospitalaria, 25(3), 350-365.
Varea, A., Disalvo, L. y González, H. (2006). Repercusión de las deficiencias de micronutrientes en salud pública. Ludovica Pediátrica, VII(1), 10-15. https://digital.cic.gba.gob.ar/handle/11746/3920
Watkins, M. L., Erickson, J. D., Thun, M. J., Mulinare, J., y Heath Jr, C. W. (2000). Multivitamin use and mortality in a large prospective study. American journal of epidemiology, 152(2), 149-162. https://doi.org/10.1093/aje/152.2.149
Wu, J., Lyons, G. H., Graham, R. D., y Fenech, M. F. (2009). The effect of selenium, as selenomethionine, on genome stability and cytotoxicity in human lymphocytes measured using the cytokinesisblock micronucleus cytome assay. Mutagenesis, 24(3), 225-232. https://doi.org/10.1093/mutage/gen074
Zhang, S., Hunter, D. J., Hankinson, S. E., Giovannucci, E. L., Rosner, B. A., Colditz, G. A., y Willett, W. C. (1999). A prospective study of folate intake and the risk of breast cancer. Jama, 281(17), 1632-1637. https://doi.org/10.1001/jama.281.17.1632
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