Bile acids colon cancer

In the bile acid/colon cancer hypothesis, colonic microbial flora is implicated as the key intermediary modulating the luminal effect of bile acids[57,64]. In another experiment we therefore examined the tropic and co-carcinogenic potential of sodium deoxycholate instilled directly into rat large bowel after exposure to azoxymethane. We further examined the effect of the anaerobicide metronidazole in modifying this potential[65]. 

It is important to note that diet is a complex mixture that contain compounds with varying activity. Chemical stimulators of colon cancer growth include bile acids, 1,2-diglycerides and prostaglandins which stem from consumption of fat. In contrast, fruits and vegetables contain substances such as carotenoids, flavonoids and fibre, which may inhibit cancer cell growth, and the risk of colon cancer appears to be mirrored by the ratio of plant sterols to cholesterol in the... 

Cheah, P.Y. and Bernstein, H. (1990). Modification of DNA by bile acids a possible fector in the aetiology of colon cancer. Cancer Lett. 49, 207-210. 

Kandell, R.L. and Bernstein, C. (1991). Bile salt/acid induction of DNA damage in bacterial and mammalian cells, implications for colon cancer. Nutr. Cancer 16, 227-238. 

D. Stamp, Antibiotic therapy may induce cancers in the colon and breasts through a mechanism involving bile acids and colonic bacteria. Medical Hypotheses, 2004, 63, 555-556. 

Micromolar quantities of RNS are generated primarily by nitric oxide synthase 2 (NOS2), an enzyme that is up-regulated during colon-cancer progression. As discussed below, deoxycholate (DOC), a hydrophobic secondary bile acid, activates the redox-sensitive transcription factor NF-kB, resulting in increased levels of NOS2 and enhanced S-nitrosylation of proteins. Additional sources of bile-acid-induced ROS and RNS are also likely. ... 

C. Bernstein, H. Bernstein, H. Garewal, P. Dinning, R. Jabi, R. E. Sampliner, M. K. McCuskey, M. Panda, D. J. Roe, L. L Heureux and C. Payne, A bile-acid-induced apoptosis assay for colon cancer risk and associated quality control studies. Cancer Res., 1999, 59(10), 2353. 

B. S. Reddy and E. L. Wynder, Metabolic epidemiology of colon cancer. Fecal bile acids and neutral sterols in colon cancer patients and patients with adenomatous polyps. Cancer, 1977, 39(6), 2533. 

T. Narisawa, N. E. Magadia, J. H. Weisburger and E. L. Wynder, Promoting effect of bile acids on colon carcinogenesis after intra-rectal instillation of N-methyl-N -nitro-N-nitrosoguanidine in rats, J. Natl. Cancer Inst., 1974, 53(4), 1093. 

S. Lechner, U. Muller-Ladner, K. Schlottmann, B. Jung, M. McClelland, J. Ruschoff, J. Welsh, J. Scholmerich and F. Kullmann, Bile acids mimic oxidative stress induced up-regulation of thioredoxin reductase in colon cancer cell lines, Carcinogenesis, 2002, 23(8), 1281. 

Many sites of exposure to bile in the body are associated with the development of cancer, e.g. the oesophagus, gallbladder and bile duct, pancreas, small intestine and colon (reviewed in ref. 2). One explanation for increased cancer at these sites could be that bile acids stimulate carcinogenesis via DNA-damaging effects. This chapter provides an overview of research conducted in relation to establishing the genotoxic and carcinogenic effects of bile acids. 

P. K. Baijal, D. W. Fitzpatrick and R. P. Bird, Comparative effects of secondary bile acids, deoxycholic and lithocholic acids, on aberrant crypt foci growth in the postinitiation phases of colon carcinogenesis, Nutr. Cancer, 1998, 31, 81. 

Y. Ueyama, Y. Monden, X. B. He, C. X. Lin, M. A. Momen, S. Mimura and A. Umemoto, Effects of bile acids on 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine-induced aberrant crypt foci and DNA adduct formation in the rat colon, J. Exp. Clin. Cancer Res., 2002, 21, 577. 

R. Kanamoto, N. Azuma, H. Suda, T. Seki, Y. Tsuchihashi and K. Iwami, Elimination of Na" -dependent bile-acid transporter from small intestine by ileum resection increase colonic tumourigenesis in the rat fed deoxycholic acid, Cancer Lett., 1999, 145, 115. 

M. R. Ballestero, M. J. Monte, O. Briz, F. Jimenez, F. Gonzalez-San Martin and J. J. G. Marin, Expression of transporters potentially involved in the targeting of cytostatic bile-acid derivatives to colon cancer and polyps, Biochem. Pharmacol., 2006, 72, 729. 

Covers, M. J., Termont, D. S., Lapre, J. A., Kleibeuker, J. H., Vonk, R. J., and van der Meer, R. (1996). Calcium in milk products precipitates intestinal fatty adds and secondary bile acids and thus inhibits colonic cytotoxicity in humans. Cancer Res. 56,3270-3275. 

Dietary Fat and Fiber and Bile Acid Excretion. In order to understand the specifics of the mechanisms whereby dietary fat influences colon cancer, the effect of type and amount of dietary fat on biliary and fecal bile acids was studied in rats (40,47,48). These... 

Thus, the excretory pattern of fecal secondary bile acids observed in these studies correlated with colon tumor incidences in animal models. These studies also suggest that high dietary intake of certain types of fat may be necessary for the full expression of risk for colon cancer. 

One hypothesis linking dietary fat to colon cancer is that cholesterol is converted to bile acids which act as promoters of carcinogenesis (58). Epidemiological studies have shown however, (38) that when beef consumption in the United States doubled (between 1940-1970) the incidence of colon cancer mortality was virtually unchanged. In addition, the incidence of colon cancer is the same in Seventh Day Adventists, who eat meat sparingly (59) and Mormons, who consume a conventional diet (60). 

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