[Development of 1,2-dimethylhydrazine-induced colonic neoplasia in rats and changes in cellular proteins of colonic mucosa]

Abstract

Development of 1,2-dimethylhydrazine (DMH) induced colonic neoplasia were studied using male Wistar rats given 120 mg DMH per kg s.c. weekly for 5 weeks. During the course of colon carcinogenesis, changes in cellular proteins of colonic mucosa were analysed by two-dimensional gel electrophoresis. Rats were sacrificed just before and at 10, 15 and 20 weeks after the initial DMH treatment together with controls. Incidence and number of colorectal tumors gradually increased. At the 20th week, colon carcinoma was found in every rat. Most tumors (92%) were found in the major flexure and the distal colon and rectum, while only 1% and 7% were found in the cecum and proximal colon, respectively. Histologically, most (92%) were classified as well differentiated or moderately differentiated adenocarcinoma. Eighty-five percent of the tumors were semipedunculated or sessile without depression, and the remainder were sessile with depression. All of the latter were carcinomas with invasion to the submucosa or further. Two-dimensional gel electrophoresis revealed 180 spots in cellular proteins before and after the initial treatment. Three new spots appeared and four spots greatly increased during the course of carcinogenesis, while one spot disappeared. The above results suggest that the appearing and increasing spots may be associated with cancer and that the disappearing spot may be associated with the normal colon.