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Although the oral route is the main way of exposure to inorganic As, the adverse gastrointestinal effects produced by chronic exposure are not well documented. The aim of the present study is to evaluate the effect of chronic exposure to As(III) on the intestinal epithelium. For this purpose, NCM460 cells, non\u2010transformed epithelial cells from the human colon, were exposed to As(III) (0.01\u20100.2\u00a0mg\/L) for 6\u00a0months and monitored for acquisition of a tumor\u2010like phenotype. Secretion of matrix metalloproteinases, histone modifications (H3 acetylation), hyperproliferation capacity, formation of floating spheres, anchorage\u2010independent growth, release of cytokine interleukin\u20108 and expression of relevant genes in colon tumorigenesis were assessed. The results show a maintained proinflammatory response from the beginning, with an increase in interleukin\u20108 secretion (\u2264570%). Downregulation of <jats:italic>CDX1<\/jats:italic> and <jats:italic>CDX2<\/jats:italic> was also observed. After 14\u00a0weeks of exposure, cells presented marked increases in matrix metalloproteinase\u20102 secretion and histone modifications. As(III)\u2010treated cells were hyperproliferative, grew in low\u2010serum media and were able to form free\u2010floating spheres. Overall, these data suggest that exposure of human colon epithelial cells to As(III) facilitates acquisition of transformed cell characteristics.<\/jats:p>","DOI":"10.1002\/jat.3778","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T14:19:33Z","timestamp":1549981173000},"page":"899-907","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Effect of chronic exposure to inorganic arsenic on intestinal cells"],"prefix":"10.1002","volume":"39","author":[{"given":"Gabriela M.","family":"Chiocchetti","sequence":"first","affiliation":[{"name":"Instituto de Agroqu\u00edmica y Tecnolog\u00eda de Alimentos (IATA\u2010CSIC)  Calle Agust\u00edn Escardino 7 46980 Paterna Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinoraz","family":"V\u00e9lez","sequence":"additional","affiliation":[{"name":"Instituto de Agroqu\u00edmica y Tecnolog\u00eda de Alimentos (IATA\u2010CSIC)  Calle Agust\u00edn Escardino 7 46980 Paterna Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1988-2985","authenticated-orcid":false,"given":"Vicenta","family":"Devesa","sequence":"additional","affiliation":[{"name":"Instituto de Agroqu\u00edmica y Tecnolog\u00eda de Alimentos (IATA\u2010CSIC)  Calle Agust\u00edn Escardino 7 46980 Paterna Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,2,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2006.06.029"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2013.01.013"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2013.09.016"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2007.125542"},{"key":"e_1_2_7_6_1","first-page":"5895","article-title":"Malignant neoplasms among residents of a blackfoot disease\u2010endemic area in Taiwan: high\u2010arsenic artesian well water and cancers","volume":"45","author":"Chen C.\u2010J.","year":"1985","journal-title":"Cancer Research"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2017.05.004"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2018.01.011"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0463.2006.apm_292.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2010.11.008"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2012.05.002"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.025"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.3.7.913"},{"key":"e_1_2_7_14_1","unstructured":"IARC. 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