Colonoscopic colostomy model in rats for colon tumorigenesis studies

A colonoscopic colostomy model for colorectal carcinogenesisand chemoprevention was developed in F344 rats. The colon wastransected at the middle of the transverse colon and suturedto two openings. The proximal opening, located on the middleline of the upper abdominal wall, was for the exit of feces.The distal one located on the left back was the colostomy forthe lower part of colorectum, which was approximately 9 cm inlength and isolated from the feces. The two openings of thecolostomy were completely separated with at least 4 cm distancebetween them. The animals were treated with 1,2-dimethylhydrazine(DMH) or methylazoxymethanol acetate (MAMAc) systemically ortopically. Colon tumors in the isolated colorectum were observedby colonoscopy. Twenty six tumors in the isolated colorectumwere found by colonoscopy with a mean latent period of 25.6weeks in 10/15 (66.6%) animals treated with DMH (30 mg/kg subcutaneously,weekly for 30 weeks). Twelve tumors were found by colonoscopywith a mean latent period of 32.8 weeks in 6/17 (35.3%) animalstreated with MAMAc (5 mg/kg enema, weekly for 35 weeks). Tumorswith 0.5 mm diameter were detected as early as 21 weeks followingthe first dose of DMH and 28 weeks following the first doseof MAMAc respectively. Video camera-assisted endoscopic examinationdetected suspected small tumors 6 weeks earlier than endoscopicevaluation alone. The number, size and location of the tumorsobserved by colonoscopy were significantly correlated with thoseobserved at necropsy. The tumor growth rate was monitored weekly.The tumor growth curve was expressed as the mean tumor diametersand calculated tumor volumes. Histological study at necropsyshowed that 48.1% of the tumors were adenomas and 51.9% wereadenocarcinomas. With a complete fecal diversion and colonoscopy,the model is potentially useful to study colon carcinogenesisand the inhibition of colon carcinogenesis.