Roles of endogenous substances and bacteria in colorectal cancer.

Because the environment of the human colon is so complex, factors which lead to the development of colorectal cancer are difficult to identify. The effects of 3 endogenous components that affect development of colorectal cancer--colonic bacteria, the mucus layer and bile acids--will be reviewed in this article. The major effects of the bacteria are deconjugation and reduction of bile acids, activation of mutagen precursors, fermentation and production of volatile fatty acids, formation of endogenous mutagens and physical adsorption of hydrophobic chemicals. The mucus layer covering the surface acts as a barrier, and its composition changes in premalignant and malignant colon tissue. Its secretion is elevated by certain plant cell wall components in the diet. Mucus has some hydrophobic properties, and its presence may alter the distribution of hydrophobic molecules. Bile acid concentration in faecal water, rather than the total bile acid concentration, determines the toxicity to epithelial cells and increased concentrations stimulate cell proliferation rates. There is evidence that elevated bile acids in the lumen can activate cellular protein kinase C, which stimulates cell proliferation. These effects are consistent with bile acids acting as tumour promoters.