Diet and Biotransformation of Carcinogenic Compounds in the Gut by Enzymes of Microflora and of Intestinal Cells

Abstract

An unfavourable diet is expected to increase colon cancer risk by elevating exposure to both endogenous and exogenous toxic, genotoxic or carcinogenic compounds. Exogenous risk factors include food contaminants such as heterocyclic amines, poly-cyclic aromatic hydrocarbons, metals, or mycotoxins. Examples of endogenous risk compounds are bile acids, reactive oxygen species (peroxides, oxygen radicals), lipid peroxidation products (4-hydroxy-alkenals, α, ß-unsaturated aldehydes) and nitrosamines. All compounds may be subject to local metabolic conversion (by the microflora or by intestinal cells) and systematically (e.g. by the liver). Metabolic conversion pathways include the formation, activation and inactivation of toxic, genotoxic and carcinogenic substances. The effect of these compounds is dependent on the concentration of reactive intermediates in the specific target tissue, which in turn is governed by pharmacokinetic factors, exposure levels, and the balance between activating and deactivating enzymes. The colon may be more susceptible to carcinogens than the liver, since lower levels of deactivating enzymes are present in intestinal cells. Moreover, exposure times to toxic compounds may be longer. Enzymes from intestinal cells as well as from the microflora may be modulated by diet. Several studies have indicated that the ingestion of complex carbohydrates may favourably alter the balance of biotransformation towards inactivation of reactive compounds. Thus, diet has an impact on health not only by allowing a reduction of exposure to exogenous and endogenous factors, but also by modulating the microflora and the enzymes of epithelial cells in such a manner that a reduced load of reactive compounds is present in the colon and ultimately delivered to cells. The consequence of reduced exposure to carcinogenic substances is a lowering of cancer risk.