Surface changes in the descending colon of rats treated with dimethylhydrazine

Male Sprague-Dawley rats were given weekly s.c. injections of 1,2-dimethylhydrazine (21 mg/kg) for period of up to 20 weeks. The descending colon of treated animals killed at 2 weekly intervals was examined for morphological change, over a 30-week period, after commencement of treatment using scanning electron microscopy, light microscopy, transmission electron microscopy, and freeze-fracture techniques. Scanning electron microscopy showed that 1,2-dimethylhydrazine treatment resulted in the progressive replacement of the normal arrangement of epithelial cells covering the luminal surface of intestinal glands with enlarged and irregularly shaped arrangements of epithelial cells, so that the entire mucosa was atypical and disorganized at 30 weeks after commencement of treatment. The changes were not readily observable using other methods of microscopy. Multiple tumors that were apparently unrelated to sites of specific morphological change erupted into the intestinal lumen through the atypical epithelium. Tumor surface cells and normal absorptive cells were compared using scanning electron microscopy and transmission electron microscopy of thin sections and freeze-fracture replicas. The results showed that tumor cells were usually smaller, more rounded, showed less regularly shaped microvilli, and had fewer particles in the apical surface membrane than on normal absorptive cells.