{"id":61334,"date":"2018-03-09T22:49:10","date_gmt":"2018-03-09T22:49:10","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/ocartoxina-a-efectos-sobre-el-adn-y-sobre-la-expresion-genica\/"},"modified":"2018-03-09T22:49:10","modified_gmt":"2018-03-09T22:49:10","slug":"ocartoxina-a-efectos-sobre-el-adn-y-sobre-la-expresion-genica","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/toxicologia\/ocartoxina-a-efectos-sobre-el-adn-y-sobre-la-expresion-genica\/","title":{"rendered":"Ocartoxina a: efectos sobre el adn y sobre la expresi\u00f3n g\u00e9nica"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Leire Arbillaga Lacunza <\/strong><\/h2>\n<p>Ocratoxina a:  efectos sobre el adn y sobre la expresi\u00f3n genica #resumen: ocratoxina a: efectos sobre el adn y sobre la expresi\u00f3n g\u00e9nica. La ocratoxina a (ota) es una micotoxina producida por las especies aspergillus y peni culi un\u00ed, que contamina gran variedad de alimentos, dando lugar a una exposici\u00f3n cr\u00f3nica humana. La ota es nefrot\u00f3xica en varias especies y carcinog\u00e9nica en roedores, pero se desconoce su mecanismo de acci\u00f3n. El fin del presente trabajo de investigaci\u00f3n ha sido profundizar en su mecanismo de toxicidad estudiando sus efectos sobre el adn y sobre la expresi\u00f3n g\u00e9nica. En primer lugar, en la linea celular renal humana hk-2, la ota indujo da\u00f1o oxidativo en el adn y un aumento de los niveles de especies reactivas de oxigeno (ero) s\u00f3lo a concentraciones citot\u00f3xicas. La n-acetil-l-cisteina, fue capaz de disminuir estos efectos. Por lo que, estos resultados suger\u00edan que el estr\u00e9s oxidativo precede a la citotoxicidad y genotoxicidad de la ota. En segundo lugar, en la misma linea celular, se observ\u00f3 una sobre-expresi\u00f3n de los genes de la cadena mitocondrial transportadora de electrones y de estr\u00e9s oxidativo. Sin embargo, los genes en respuesta al da\u00f1o en el adn estaban reprimidos. Finalmente, en ratas fisher 344 macho, tras una administraci\u00f3n oral repetida, se observ\u00f3 una disminuci\u00f3n de las defensas antioxidantes en el ri\u00f1on, asi como, represi\u00f3n de los genes relacionados con el metabolismo y el transporte. Los genes de respuesta al da\u00f1o en el adn no se modificaron. En conclusi\u00f3n, los resultados de este trabajo apoyan la hip\u00f3tesis de que la ota es un compuesto genot\u00f3xico que no reacciona con el adn, y que produce su efecto t\u00f3xico a trav\u00e9s de un mecanismo epigen\u00e9tico atribuible al estr\u00e9s oxidativo celular. Por lo que, se puede establecer un umbral de toxicidad a partir del cual fijar unos limites tolerables de exposici\u00f3n humana.   ochratoxin a: effects on dna and gene expression ochratoxin a (ota) is a mycotoxin produced by aspergillus and penicillium species that contaminate a variety of food items, resulting in chronic human exposure. Ota is nephrotoxic in several species and produces renal tumours in rodents, but its mechanism of action is unknown. Therefore, the aim of the present research project was to provide more insights into the molecular mechanism of ota toxicity by focusing on the effects on dna integrity and gene expression. Firstly, in the human kidney cell line hk-2, ota did not induce dna damage at noncytotoxic concentrations, but oxidative dna damage and increased level of reactive oxygen species (ros) were observed at cytotoxic concentrations. Furthermore, n-acetyl-l-cysteine was able to produce a slight protective effect against ota-induced ros increase, cytotoxicity and dna damage. These results suggested that oxidative stress precedes cytotoxicity and genotoxicity. Secondly, in the same cell line, up-regulation of genes involved in the mitochondrial electr\u00f3n transport chain and in oxidative stress response was observed. However, genes related to dna damage response were down-regulated. Finally, in male fisher 344 rats, after a repeated oral administration, antioxidant defence inhibition was observed in kidney, as well as, down-regulation of metabolism and transport-related genes. Dna damage response genes were not affected. Altogether, the results of this work support the nypothesis that ota isa dna non-reactive genotoxic compound that produces its toxic effect through an epigenetic mechanism attributable to cellular oxidative stress. Therefore, a toxicicity threshold could be established for determining tolerable human exposure 1 i mits<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Ocartoxina a: efectos sobre el adn y sobre la expresi\u00f3n g\u00e9nica<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Ocartoxina a: efectos sobre el adn y sobre la expresi\u00f3n g\u00e9nica <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Leire Arbillaga Lacunza <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Navarra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 14\/11\/2007<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Adela Lopez De Cerain Salsamendi<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Jos\u00e9 alfredo Martinez hernandez <\/li>\n<li>miquel Borras suarez (vocal)<\/li>\n<li>Jos\u00e9 vicente Castells ripoll (vocal)<\/li>\n<li>jozef Van delft (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Leire Arbillaga Lacunza Ocratoxina a: efectos sobre el adn y sobre la expresi\u00f3n genica #resumen: ocratoxina a: [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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