Chemical carcinogens and their mode of action in colonic neoplasia

Abstract

Summary Epidemiologic considerations, geographic pathology, and migrant studies definitely indicate that cancer in the gastrointestinal tract, in particular in the stomach and in the colon is mediated by environmental factors, especially dietary components. In recent years specific chemicals which induce cancer of the colon in animal systems have been discovered. Thus, model experiments are currently being performed to study the actions of environmental factors on the effectiveness of such chemicals in leading to colorectal cancer. Thus, hopefully, these experiments will pinpoint those agents in the environment which exert a controlling influence in this disease. Information on the metabolism of the chemical carcinogens affecting the lower gut indicates that certain of the metabolic steps may be performed in the liver, after which active metabolites are secreted in the bile in a protected conjugated form. The key ultimate carcinogen is then released in the colon by enzymes produced by bacterial microflora. A number of alternative pathways can also develop active carcinogens by microbial action in the gut, or by metabolic activation mediated by enzyme systems in colonic epithelium. Thus, studies of the effects of environmental agents in modifying flora in the lumens of specific enzyme systems in the intestinal wall are important in understanding the complex problems related to the etiology of colonic cancer.