Advances in Clinical and Experimental Medicine
2006, vol. 15, nr 6, November-December, p. 983–988
Publication type: original article
Language: English
Colonic Carcinogenesis in an Experimental Model of Chronic Colitis in Rats
Proces karcynogenezy w doświadczalnym modelu przewlekłego zapalenia okrężnicy u szczurów
1 1st Department of General, Gastroenterological, and Endocrine Surgery, Silesian Piasts University of Medicine in Wrocław, Poland
Abstract
Background. The study of the adenoma−carcinoma sequence in an animal model of chronic colitis resembling human ulcerative colitis is essential to understand the pathogenesis of the process and to allow the testing cancer chemopreventive agents.
Objectives. The aim was to establish a model of chronic colitis to study the relationship between inflammation and cancer development as well as to elucidate the adenoma−to−carcinoma cascade demonstrated by the p53 and Ki67 markers and dysplastic lesions (high and low grade). Additionally, the metastatic affection of liver tissue was investigated.
Material and Methods. An experimental model of colitis and carcinogenesis in 50 two−month−old Wistar rats was used. First colitis was induced using acetic acid and histologically proved, then carcinogenesis in two groups of animals (healthy and with induced colitis) was studied. Azoxymethane was used as the carcinogen.
Results. Colonic adenocarcinoma developed in 30% of the colitis−induced group and in 20% of the group without induced colitis but receiving the carcinogen. Dysplasia preceded the development of colonic adenocarcinoma. Ki67 and p53 positivity was an early sign of colonic malignancy in both dysplastic (mostly high grade) and carcinoma lesions. Liver tissue was affected by metastatic carcinoma only in those animals with chronic colitis.
Conclusion. Chronic colitis resembling human ulcerative colitis leads to the development of colonic adenocarcinoma. In the colitis−induced group the process of carcinogenesis was more frequent and expansive than in the healthy animals.
Streszczenie
Wprowadzenie. Badania dotyczą zwierzęcego modelu przewlekłego zapalenia okrężnicy odpowiadającego ludzkiemu wrzodziejącemu zapaleniu jelita grubego. Poglądy na temat karcynogenezy u pacjentów z zapalnymi chorobami jelit są dotychczas nieustalone i kontrowersyjne.
Cel pracy. Zbadanie karcynogenezy na eksperymentalnym modelu zapalenia jelita grubego u szczura.
Materiał i metody. Do badań użyto 50 2−miesięcznych szczurów szczepu Wistar. Doświadczenie podzielono na dwa etapy. Pierwszy to indukcja zapalenia jelita grubego przez doodbytnicze podanie kwasu octowego, a drugi to karcynogeneza wywołana dootrzewnowym podaniem azoksymetanu: w pierwszej grupie przy zmienionym zapalnie jelicie, w drugiej przy jelicie zdrowym. Metodą immunohistochemiczną oceniono p53 i Ki67. Dodatkowo uwzględniono zmiany o charakterze dysplazji (low and high grade). Oceniono także tkankę wątrobową pod względem zmian o charakterze przerzutowym.
Wyniki. W obu grupach poddanych działaniu karcynogenu nowotwory rozwinęły się odpowiednio w 30 i 20% (o 10% częściej w grupie zwierząt cierpiących na zapalenie okrężnicy). Zmiany histopatologiczne (dysplazja high and low grade) wyprzedzały rozwój nowotworu. Reakcje Ki67 i p53 były dodatnie w zmianach dysplastycznych (high grade) i nowotworowych. U zwierząt z przewlekłym procesem zapalnym w jelicie dodatkowo wystąpiły zmiany o charakterze przerzutowym do wątroby.
Wnioski. Przewlekły proces zapalny o charakterze colitis, odpowiadający wrzodziejącemu zapaleniu okrężnicy u ludzi, pobudza rozwój raka jelita grubego. W grupie zwierząt chorych na zapalenie okrężnicy proces ten jest częstszy i bardziej ekspansywny.
Key words
colitis, dysplasia, colonic carcinogenesis, rats
Słowa kluczowe
zapalenie okrężnicy, dysplazja, karcynogeneza, szczury
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