Development of colonic neoplasms and expressions of p53 and p21 proteins in experimental colitis of mice induced by dextran sulfate sodium

The mechanisms underlying the frequent development of colorectal carcinomas in patients with ulcerative colitis (UC) are still not understood. This st udy was conducted to investigate whether p53 and p21 protein expressions co ntribute to carcinogenesis in an experimental model with dextran sulfate so dium (DSS) treatment, and to establish if this colitis model is suitable fo r study of cancer development in UC. A total of 40 mice were subjected to four administration cycles of 4% DSS f or 7 days followed by plain water for the subsequent 14 days. The 33-surviv ing mice were sacrificed to examine the malignant transformation of colonic mucosa morphologically and to determine p53 and p21 expressions immunohist ochemically. After DSS treatment periods, there were marked irregularities in the mucosa l layer, the thickness of the entire bowel wall and the shortness of the co lon. Histologically, tumors were found in 13 out of 33 (39.4%) mice. These 13 cases included 9 with a solitary lesion and 4 with double tumors. There were occurrences of invasive carcinomas in 8 lesions, high-grade dysplasia in 3 lesions and low-grade-dysplasia in 6 lesions. One presented with a pol ypoid tumor, 5 mm in diameter, while 16 had small flat lesions. There were 13 tumors on the left-sided colon, as opposed to 4 on the right-sided colon . Histological differentiation of invading carcinomas revealed that 6 out o f 8 lesions were comprised of well differentiated adenocarcinomas, while 2 were moderately differentiated adenocarcinomas. Overexpression of p53 prote in was found in 4 out of 8 invasive carcinomas, 2 out of 3 high-grade dyspl asia cases and 2 out of 6 low-grade dysplasia cases, whereas only 1 out of 8 with invasive carcinoma was positive for p21. This experimental colitis model suggests that p53 and p21 protein expressio ns may contribute to carcinogenesis in DSS-induced colitis in mice and appe ars suitable to study cancer development in UC.