Colonoscopic colostomy model in rats for colon tumorigenesis studies

A colonoscopic colostomy model for colorectal carcinogenesis and chemoprevention was developed in F344 rats. The colon was transected at the middle of the transverse colon and sutured to two openings. The proximal opening, located on the middle line of the upper abdominal wall, was for the exit of feces. The distal one located on the left back was the colostomy for the lower part of colorectum, which was approximately 9 cm in length and isolated from the feces. The two openings of the colostomy were completely separated with at least 4 cm distance between them. The animals were treated with 1,2-dimethylhydrazine (DMH) or methylazoxymethanol acetate (MAMAc) systemically or topically. Colon tumors in the isolated colorectum were observed by colonoscopy. Twenty six tumors in the isolated colorectum were found by colonoscopy with a mean latent period of 25.6 weeks in 10/15 (66.6%) animals treated with DMH (30 mg/kg subcutaneously, weekly for 30 weeks). Twelve tumors were found by colonoscopy with a mean latent period of 32.8 weeks in 6/17 (35.3%) animals treated with MAMAc (5 mg/kg enema, weekly for 35 weeks). Tumors with 0.5 mm diameter were detected as early as 21 weeks following the first dose of DMH and 28 weeks following the first dose of MAMAc respectively. Video camera-assisted endoscopic examination detected suspected small tumors 6 weeks earlier than endoscopic evaluation alone. The number, size and location of the tumors observed by colonoscopy were significantly correlated with those observed at necropsy. The tumor growth rate was monitored weekly. The tumor growth curve was expressed as the mean tumor diameters and calculated tumor volumes. Histological study at necropsy showed that 48.1% of the tumors were adenomas and 51.9% were adenocarcinomas. With a complete fecal diversion and colonoscopy, the model is potentially useful to study colon carcinogenesis and the inhibition of colon carcinogenesis.