Early mucosal changes in dimethylhydrazine-induced colonic carcinogenesis in rats

Early mucosal changes in dimethylhydrazine (DMH)-induced colonic carcinogenesis were investigated in 12 rats. These rats received subcutaneous injections of DMH in a dose of 15 mg/kg/week. Two rats each were killed at 6, 8, 10, 14, 18 and 22 weeks after initiation of the DMH-treatment. Overt carcinomas developed in 3 out of 4 rats killed after the 18th week of DMH-treatment. Histopathologically, epithelial dysplasia was present in the flat colonic mucosa of all 6 rats killed after the 14th week of DMH-treatment. Neither grossly visible tumors nor histopathological dysplasia was present in the colon of the 6 rats killed before the 14th week of DMH-treatment. However, cytophotometric DNA analysis disclosed that significant increases in proliferative activity of mucosa had occurred 4 weeks before the appearance of histopathological dysplasia, and 8 weeks prior to development of grossly visible tumors. Therefore, changes in the flat mucosa of a tumor-bearing colon represents a primary precancerous condition.