Cell turnover and colon tumor development

Abstract

The proliferative characteristics of the large bowel are determined genetically and can vary over a wide range, the lower range being resistant to chemically induced tumors and the upper range expressing susceptibility. Basically, the colon has a relatively high level of cell renewal. It can be further elevated or depressed by a number of dietary and environmental conditions. A hyperproliferative state has been induced by the presence of carrageenan, Citrobacter freundii, nonspecific injury, or dietary factors such as high levels of bile acids. The effect of high proliferation levels is to produce more S-phase cells, which are sensitive to DNA damage, to increase the risk of neoplastic transformation and to shorten the tumor latency period. In animal models, hyperactivity has meant enhanced tumor incidence. A hypoproliferative state has been induced in the colon of man and mouse. Experimentally, the net effect of lower proliferative levels has been to reduce colon tumor incidence. It remains to be determined whether clinical trials involving hypoproliferation can be maintained chronically and are an effective means of reducing colon tumor incidence in high-risk groups.