Effect of dietary components on the pathobiology of colonic epithelium: possible relationship with colon tumorigenesis.

The concept that diet plays an important role in the initiation and/or development of various types of tumors in man and experimental animals is well documented. The etiology of colon cancer is complex and multifactorial in nature, and there is little information on the dietary components that may act as initiators during colon tumorigenesis. We have evaluated various dietary heterocyclic mutagenic amines present in a typical "Western" diet for their nuclear damaging effect (presumably a genotoxic response) on the colonic epithelium of C57BL/6J mice in vivo. Among the mutagenic amines studied 2-amino-3,4-dimethylimidazo(4,5-f)quinoline and 2-amino-3-methylimidazo(4,5-f)quinoline were very potent inducers of nuclear aberrations. These observations provide us with clues that our daily diet may contain colon-specific genotoxic components. Promotional effects of dietary fat and/or bile acids on colon tumorigenesis have been well studied. Dietary levels of calcium (0.1, 0.5 or 1.0% by weight) appear to modify the toxicity of orally administered fat or cholic acid (assessed by quantifying cell proliferation). The colons of animals consuming 0.1% or 0.5% calcium diet were more susceptible to the toxicity, whereas the colons of those consuming a 1.0% calcium diet appeared more like control colons. These studies demonstrate a profound effect of dietary constituents on the pathobiology of the colonic epithelium which may have a marked influence on the colon tumorigenesis.