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, 85 (8), 863-71

Carcinogenicity of Deoxycholate, a Secondary Bile Acid

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Carcinogenicity of Deoxycholate, a Secondary Bile Acid

Carol Bernstein et al. Arch Toxicol.

Abstract

High dietary fat causes increased bile acid secretion into the gastrointestinal tract and is associated with colon cancer. Since the bile acid deoxycholic acid (DOC) is suggested to be important in colon cancer etiology, this study investigated whether DOC, at a high physiologic level, could be a colon carcinogen. Addition of 0.2% DOC for 8-10 months to the diet of 18 wild-type mice induced colonic tumors in 17 mice, including 10 with cancers. Addition of the antioxidant chlorogenic acid at 0.007% to the DOC-supplemented diet significantly reduced tumor formation. These results indicate that a high fat diet in humans, associated with increased risk of colon cancer, may have its carcinogenic potential mediated through the action of bile acids, and that some dietary anti-oxidants may ameliorate this carcinogenicity.

Figures

Fig. 1
Fig. 1
Role of bile acids in progression to cancer
Fig. 2
Fig. 2
Normal areas of colons of mice from 4 different dietary groups. Diet supplements fed for 10 months: a none; b CGA; c DOC; d DOC + CGA. Images taken at 200× magnification. Bars show 0.2 mm. H&E staining
Fig. 3
Fig. 3
Opened mouse proximal colon segments showing tumors after feeding the DOC-supplemented diet. Each opened colon segment is shown (top images), with the macroscopically observed tumors identified with closed dashed curves (bottom images). Left images: 8 months on diet; Right images: 10 months on diet
Fig. 4
Fig. 4
Two areas of mouse colonic mucosa with sessile serrated adenomas (a, b) and two areas with adenocarcinomas (c with a stage T1, and d with a stage T2 cancer). From mice fed the DOC supplemented diet for 10 months. Images taken at 200× magnification. Bars show 0.2 mm. H&E staining

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