Colorectal Oncogenesis and Inflammation in a Rat Model Based on Chronic Inflammation due to Cycling DSS Treatments

Åsa Håkansson,Göran Molin,Siv Ahrné,Bengt Jeppsson,Margareta Nyman,Diya Adawi,Camilla Bränning,Marie-Louise Hagslätt

doi:10.1155/2011/924045

Åsa Håkansson, Göran Molin + Show 6 more

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https://doi.org/10.1155/2011/924045

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Abstract

Inflammation is known to be linked with development of colorectal cancer, and the aim was to assess the malignant potential and degree of inflammation in a dextran-sulphate-sodium-(DSS-) induced cyclic colonic tumour model (CTM) in rats and to compare it with the azoxymethane-(AOM-) induced CTM model. Tumours developed in both groups, although, in the DSS group, the colonic mucosa appeared edematous and the number of haemorrhagic erosions and quantity of dysplastic lesions were higher as well as the mucosal concentration of myeloperoxidase and faecal viable count of Enterobacteriaceae. The livers were affected as evaluated by steatosis, parenchymal loss, haemorrhage, and inflammatory infiltrations, and higher proportions of acetate and lower proportions of butyrate in colonic content were found. The DSS model seems to mimic the clinical situation and may be valuable for investigation of inflammation-related dysplasia and colon cancer, as well as for altered liver function by endogenous inflammatory mediators.

Highlights

Chronic inflammation is characterised by a continued active inflammatory response and tissue destruction, and it seems to be a driving mechanism for promoting the development of carcinoma in colon and rectum of patients suffering from ulcerative colitis (UC), one of the major forms of the idiopathic inflammatory bowel diseases [1]
Dysplasia describes architectural and cytological abnormalities in the epithelium that predispose an organ to cancer development, and dysplasia has been indicated as an indicator of malignancy in UC [5]
Chronic colitis associated with dysplasia has been found in rats after dextran sulphate sodium (DSS) exposure [62]

Summary

Introduction

Chronic inflammation is characterised by a continued active inflammatory response and tissue destruction, and it seems to be a driving mechanism for promoting the development of carcinoma in colon and rectum of patients suffering from ulcerative colitis (UC), one of the major forms of the idiopathic inflammatory bowel diseases [1]. Compared to the general population, long-term UC patients have high risk of developing colorectal cancer, which increases as the extent and duration of the disease increase [2]. Mucosal inflammation may lead to colonic carcinogenesis through different mechanisms, such as induction of genetic mutations, increased cryptal cell proliferation, changes in crypt cell metabolism and bile-acid enterohepatic circulation, and alterations in bacterial flora [3, 4]. The colonic epithelium provides a critical barrier to protect the host from resident commensal and pathogenic microbes. In patients with adenocarcinoma of the large bowel, disruption of the intestinal barrier is assumed, and findings suggest that intestinal bacteria translocate from the bowel in large numbers [6]

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