The chronic exposure to low doses of endosulfan increases the expression of proinflammatory molecules, and induces leukemia and lymphoma in mice.

Abstract

Event Abstract Back to Event The chronic exposure to low doses of endosulfan increases the expression of proinflammatory molecules, and induces leukemia and lymphoma in mice. Galina P. Zaitseva1*, Martha C. Tellez-Bañuelos1, Jorge Peregrina1 and Jesse Haramati1 1 Universidad de Guadalajara, Departamento de Biologia Celular Molecular, CUCBA, Mexico INTRODUCTION. Endosulfan, a pesticide widely used in Mexico, has been shown to have lymphoproliferative effects and may also facilitate the development of cancer. OBJECTIVE. To assess the effect of chronic exposure to low doses of endosulfan on the expression of adhesion molecules in the colon, levels of cytokines in serum, and histopathological changes in the tissues of spleen, colon and liver. MATERIALS AND METHODS. Commercially-sourced Endosulfan was diluted in olive oil and administered (2mg/kg) to mice of both sexes via oral ad gavage for 24 weeks. In the control group only olive oil was administered. Over a 52 weeks period, two mice (male and female) per week from both experimental groups were euthanized with 0.1ml subcutaneous pentobarbital. Serum levels of the cytokines IL-6, IL-10 and TNF-alpha were determined using a commercial ELISA kit (Abcam). The colons were fixed in 10% formalin and processed for histology; the resulting sections were stained using a conventional hematoxylin-eosin protocol. The immunohistochemical staining was performed using monoclonal antibodies directed to P-selectin and ß-catenin and developed with an avidin-biotin kit. RESULTS. The LD50 of Endosulfan was determined to be 8mg/kg for females and 11.5 mg/kg for males. The sublethal dose used in this study caused acute inflammation of the colon from week 3 and significantly increased serum IL-6 and P-selectin expression in the colon from week 5 of pesticide administration in females and from week 7 of administration in males. After 12 weeks of endosulfan exposure the inflammation of the colon progressed to severe chronic colitis with precancerous elements; after 24 weeks high levels of TNF-a were observed. Serum IL-10 was found to be increased by 7 and 24 weeks of exposure. At 24 weeks of exposure, ß-catenin was found to be strikingly expressed in aberrant crypts. At 30 weeks we observed positive staining in spleen and liver for the leukemia markers CD34 CD3 and PAX-5. At 52 weeks we observed the evolution of this leukemia to solid tumors pathologically graded as lymphoma. CONCLUSIONS. Chronic exposure to endosulfan, even at very low doses, induces over-expression of molecules that indicate that an expanded inflammatory process in the colon causes severe chronic colitis. Additionally, administration of Endosulfan induces rapid development of aberrant crypts as precancerous elements in the murine colon and later term lympho-proliferative tumors. These effects were observed in both sexes, but were more rapid and more pronounced in females. Keywords: Cytokines, Endosulfan, pesticide, P-Selectin, Inflammation, Cancer, Leukemia, Lymphoma, mouse model Conference: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015. Presentation Type: Poster Presentation Topic: Tumor immunology Citation: Zaitseva GP, Tellez-Bañuelos MC, Peregrina J and Haramati J (2015). The chronic exposure to low doses of endosulfan increases the expression of proinflammatory molecules, and induces leukemia and lymphoma in mice.. Front. Immunol. Conference Abstract: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología. doi: 10.3389/conf.fimmu.2015.05.00064 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 29 May 2015; Published Online: 14 Sep 2015. * Correspondence: PhD. Galina P Zaitseva, Universidad de Guadalajara, Departamento de Biologia Celular Molecular, CUCBA, Guadalajara, Mexico, galina.mex@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Galina P Zaitseva Martha C Tellez-Bañuelos Jorge Peregrina Jesse Haramati Google Galina P Zaitseva Martha C Tellez-Bañuelos Jorge Peregrina Jesse Haramati Google Scholar Galina P Zaitseva Martha C Tellez-Bañuelos Jorge Peregrina Jesse Haramati PubMed Galina P Zaitseva Martha C Tellez-Bañuelos Jorge Peregrina Jesse Haramati Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.