Depletion of enteroendocrine and mucus‐secreting cells is associated with colorectal carcinogenesis severity and impaired intestinal motility in rats

This study investigated the relationship between enteroendocrine and mucus‐secreting cells distribution, the severity of colonic mucosal injury and intestinal motility in experimental colorectal carcinogenesis. Using a standardized murine model of colorectal carcinogenesis, eight‐weeks‐old female Wistar rats weighting 147.30 ± 29.15g were randomized into two groups receiving a subcutaneous injection of 0.9% saline (control) or the chemical carcinogen 1,2‐dimethylhydrazine (DMH) at 20 mg/kg per week during 10 weeks. Aberrant crypt foci (ACF) were more frequent in DMH group compared to control group ( P  < 0.001). The number of enteroendocrine and mucus‐secreting cells, and intestinal motility was reduced in DMH animals ( P  < 0.05). The distribution of enteric neurons was similar in both groups. In DMH animals there was a direct correlation between colonic motility and distribution of enteroendocrine ( R 2  = 0.68, P  < 0.05) and mucus‐secreting cells ( R 2  = 0.77, P  < 0.05). Inverse correlation between the number of ACF, mucus‐secreting cells ( R 2  = −0.57, P  < 0.05), and enteroendocrine cells ( R 2  = −0.74, P  < 0.05) was also observed. There was inverse correlation between the severity of the mucosal lesion, the number of mucus‐secreting cells ( R 2  = −0.83, P  < 0.05) and enteroendocrine cells ( R 2  = −0.96, P  < 0.05). There was a direct correlation between nucleolar organizer regions (AgNOR) and ACF number ( R 2  = 0.62; P  < 0.01). Inverse correlation was also found between AgNOR, the number of mucus‐secreting cells ( R 2  = −0.76; P  < 0.001), and enteroendocrine cells ( R 2  = −0.86; P  < 0.001). Taken together, the results indicated that colonic malignant transformation is related to depletion of mucus‐secreting and enteroendocrine cells, which was a useful indicator of the evolutionary status of intestinal neoplasm, partially explaining the intestinal motility disorders in the early stages of colorectal carcinogenesis. Microsc. Res. Tech. 79:3–13, 2016 . © 2015 Wiley Periodicals, Inc.