SBIR-STTR Award

The objectives of this research are to study the mechanism of carcinogenesis and chemoprevention of colorectal cancer. Human colorectal cancer is a major problem in the United States and is second only to lung cancer as a cause of death. A surgical bypass colostomy model to study colorectal carcinogenesis in rats will be developed. In this model, a short loop of colon at the junction of the transverse and descending colon will be placed surgically out of the abdominal wall to create two openings. The proximal one is the exit for feces and the distal one is for introduction of carcinogens and other modifiers of carcinogenesis. A micro colonoscopic technique will be developed to monitor the progress of tumorigenesis in the colon. In the Phase I project, the bypass colostomy model will be performed in Sprague-Dawley rats. The effects of the carcinogens, 1,2-dimethylhydrazine, methylazoxymethanol acetate and N-methyl-N-nitroso urea will be tested by applying locally via colostomy and/or systemically. The tumorigenic response of the bypassed colon with respect to the route of carcinogen administration will be evaluated.Awardee's statement of the potential commercial applications of the research:The model will be useful as a screening assay for colon carcinogens, inhibitors and promoters of colon carcinogenesis.

The mortality rate of colorectal cancer is second only to lung cancer. One of the strategies to reduce human cancer is by chemoprevention. The objectives of this proposed research are to study colon carcinogenesis and the inhibition of colon carcinogenesis using a new colonoscopic model in rats. In the Phase I feasibility study the new model was developed and the optimal conditions were established for the colonoscopic study of chemically induced carcinogenesis. The latent period, incidence, number, size, location and progression of the colon tumors can be determined by weekly colonoscopy. Video camera-assisted colonoscopy can identify neoplasms earlier than normal colonoscopy, and record the data for documentation and further analysis. This Phase II research will further develop this model to be used in the investigation of two-stage carcinogenesis of colon cancer, the carcinogenicity of human fecal mutagens, the effects of inhibitors on the progression of colon carcinogenesis. An orthotopic transplantable colon tumor model will be developed for chemotherapeutic studies.