A Novel Modified Model for Induction of Intestinal Adenomas in Female Mice
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Hellenic Journal of Surgery (2018) 90:6, 289-292
A Novel Modified Model for Induction of Intestinal Adenomas in Female Mice Angelou A1, Andreatos N2, Antoniou E3, Zacharioudaki Argiro4, Karamperi Maria4, Karampela Eleftheria4, Tsarea Kalliopi4, Gerakis S4, Theodoropoulos G1, Damaskos X3, Garmpis N3, Yuan C2,5, Xiao W2,6, Theocharis S7, Zografos G1, Pikoulis E1, Margonis GA2, Papalois A4
Abstract Background: An azoxymethane/dextran sulfate sodium (AOM/DSS) protocol has been developed for the induction
in an animal model of the precancerous stages of colitis-associated carcinogenesis, by modification of the established (AOM/DSS protocol for carcinogenesis. Methods: Female C57BL6 mice were treated with a single intraperitoneal dose (10 mg/kg of body weight) of AOM followed by three, 5-day, cycles of oral DSS, at different dosages, with each cycle interrupted by a 2-week rest period. Results: The 3 mice in the group that were given three, 5-day, cycles of oral 2.5 % DSS all developed colonic adeno-
mas with dysplastic lesions, but none had developed adenocarcinoma at 60 days. In contrast, of 6 mice treated with AOM administration along with either three, 5-day, cycles of 3.0% DSS or three, 7-day, cycles of 2.5% DSS, 5 had developed cancer at day 84 of the experiment. These results suggest that the administration of three, 5-day, cycles of 2.5% DSS following an initial dose of AOM may successfully induce adenoma formation in female C57BL6 mice at day 60, without the concurrent presence of carcinoma. Conclusion: This modification of the widely used AOM/DSS protocol for induction of colonic carcinoma may
constitute a novel approach for investigating colitis-related colonic adenomas. Key words: AOM/DSS; inflammatory bowel disease; animal model; adenoma
Introduction Individuals with inflammatory bowel disease (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), are at risk of developing colitis-associated colorectal cancer (CAC), at a rate in proportion to the duration and extent 1 st
1 Department of Surgery, “Hippokrateion” Hospital, National and Kapodistrian University of Athens, Greece
2
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A. 3 nd 2 Department of Surgery, “Hippokrateion” Hospital, National and Kapodistrian University of Athens, Greece 4 Experimental Research Center ELPEN Pharmaceuticals, S.A. Inc., Co., Pikermi, Greece 5 Department of General Surgery, Peking University Third Hospital, Beijing, P.R. China 6 Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, P.R. China 7 Department of Pathology, National and Kapodistrian University of Athens, Greece Corresponding author: A. Papalois PhD, KGSJ, AMACS Experimental Research Center, ELPEN Pharmaceuticals 95, Marathonas Avenue, 19009 Pikermi, Attiki, Greece e-mail: [email protected] Received Nov 25, 2018; Revised Dec 19, 2018; Accepted Jan 14, 2019 Hellenic Journal of Surgery 90
of their disease [1, 2]. CAC development is known to be a multi-step process, with a
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