title: Depletion of enteroendocrine and mucus-secreting cells is associated with colorectal carcinogenesis severity and impaired intestinal motility in rats.
abstract: 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.
authors.affiliation: Department of Structural Biology, Federal University of Alfenas, Minas Gerais, 37130-000, Brazil.
authors.forename: Rômulo Dias
authors.initials: RD
authors.lastname: Novaes
authors.affiliation: Department of Pharmaceutical Sciences-Health area, Federal University of Juiz de Fora, Minas Gerais, 35010-172, Brazil.
authors.forename: Priscila Lima
authors.initials: PL
authors.lastname: Sequetto
authors.affiliation: Department of Animal Biology, Federal University of Viçosa, Minas Gerais, 36570-000, Brazil.
authors.forename: Reggiani
authors.initials: R
authors.lastname: Vilela Gonçalves
authors.affiliation: Department of General Biology, Federal University of Viçosa, Minas Gerais, 36570-000, Brazil.
authors.forename: Marli Carmo
authors.initials: MC
authors.lastname: Cupertino
authors.affiliation: Department of General Biology, Federal University of Viçosa, Minas Gerais, 36570-000, Brazil.
authors.forename: Eliziária Cardoso
authors.initials: EC
authors.lastname: Santos
authors.affiliation: Institute of Biological Sciences Federal University of Para, PA, 66075-110, Brazil.
authors.forename: Vanessa Joia
authors.initials: VJ
authors.lastname: Mello
authors.affiliation: Department of General Biology, Federal University of Viçosa, Minas Gerais, 36570-000, Brazil.
authors.forename: Marta Rocha
authors.initials: MR
authors.lastname: Araújo
authors.affiliation: Department of General Biology, Federal University of Viçosa, Minas Gerais, 36570-000, Brazil.
authors.forename: Edson
authors.initials: E
authors.lastname: Silva
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Viçosa, Minas Gerais, 36570-000, Brazil.
authors.forename: Tânia Toledo
authors.initials: TT
authors.lastname: Oliveira
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D058739:Aberrant Crypt Foci / Q000473:pathology; D000818:Animals; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D017615:Enteric Nervous System; D019858:Enteroendocrine Cells / Q000473:pathology*; D005260:Female; D005769:Gastrointestinal Motility / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019813:1,2-Dimethylhydrazine
keywords: aberrant crypt foci; histomorphometry; intestinal epithelium; large intestine