Stimulation of mutagen production in human feces by bile and bile acids

Tassell, Roger L. Van; MacDonald, D K; Wilkins, Tracy D.

doi:10.1016/0165-7992(82)90048-3

Cited by 38 publications

(17 citation statements)

References 9 publications

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“…Among components con tributing to faecal mutagenicity are reactive glyceryl ethers, known as fecapentaenes. Their biosynthesis might be stimulated by bile salts [29]. In general conjugated bile salts have less or no genotoxic effects and unconjugated dihydroxy and monohydroxy bile salts are more genotoxic.…”

Section: Genotoxicity and Mutagenicitymentioning

confidence: 99%

Role of bile acids in colorectal carcinogenesis

Nagengast

Grubben

Munster

1995

European Journal of Cancer

316

180

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Dietary factors are considered important environmental risk determinants for colorectal cancer development. Epidemiological studies have shown that a high fat (or meat) intake is associated positively and a high starch, fibre (non-starch polysaccharide), vegetable and fruit intake negatively with colorectal cancer incidence. One mechanism by which these effects are possibly exerted is through the metabolism of secondary bile acids. Secondary bile acids are formed after enzymatic deconjugation and dehydroxylation of primary bile acids in the large bowel by anaerobic bacteria. It has been shown that these compounds can have tumour-promoting capacities in animal experiments. In epidemiological studies, colonic cancer risk is related to the faecal bile acid concentration. In serum and bile of patients with colonic adenomas, more deoxycholic acid was detected than in healthy controls. Secondary bile acids are toxic to several cell systems at physiological concentrations. The exact mechanism by which these amphiphilic molecules exert their action is not well understood. It might act through membrane damage, intracellular mitochondrial action or genotoxic effects. So far the evidence that bile acids are involved in colonic carcinogenesis is largely circumstantial. It is, however, well accepted that environmental factors, such as dietary habits influence genetic susceptibility. Bile acids could play a promoting role in this process.

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Section: Genotoxicity and Mutagenicitymentioning

confidence: 99%

Role of bile acids in colorectal carcinogenesis

Nagengast

Grubben

Munster

1995

European Journal of Cancer

316

180

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“…Bile acids have been shown to express cancer~pmmoting pr~ perties which are modified by dietary factors (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). In particular, fiber, fat and calcium have received increased attention for their ability to induce changes in the metabolism of bile acids which affect their potential for promoting the development of experimental colon cancer (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”

mentioning

confidence: 99%

Fecal bile acid excretion and composition in response to changes in dietary wheat bran, fat and calcium in the rat

Borum¹,

Shehan²,

Fromm³

et al. 1992

Lipids

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The effect and possible interactive influence of different dietary amounts of wheat bran, fat and calcium on the fecal excretion, concentration and composition of bile acids was studied in Fischer-344 rats. The fecal bile acids were analyzed using gas-liquid chromatography. Dietary wheat bran increased both total bile acid excretion and fecal weight without changes in fecal bile acid concentration. The proportion of fecal hyodeoxycholic acid decreased with increasing dietary fiber, whereas that of lithocholic and deoxycholic acids increased significantly with fiber intake. The percent content of fecal chenodeoxycholic acid did not change. Increasing dietary fat led to an increase in bile acid excretion without changes in either fecal weight or bile acid concentration. In contrast, the level of dietary calcium did not affect the total excretion of bile acids. However, since calcium increased the fecal weight, it consequently diluted bile acids and decreased their fecal concentration. Dietary fat and calcium had no influence on fecal bile acid composition. There were no interactive effects of wheat bran, fat and calcium on fecal bile acids. The finding in this study that dietary fiber, fat and calcium induce significant changes in fecal bile acids may be of relevance to the potential of bile acids to promote carcinogenesis.

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“…Preparation and extraction of autoclaved feces. We have previously described our methods for preparing and extracting diluted autoclaved feces (35). Briefly, frozen fecal samples were thawed, thoroughly mixed, dispensed into culture tubes, and anaerobically autoclaved.…”

Section: Methodsmentioning

confidence: 99%

“…In vitro incubations. Production of this mutagen in fresh feces was followed as previously described (35); we mixed anaerobically 5 g of fresh feces with 5 ml of dilution fluid and incubated the mixture at 37°C for 72 to % h. The feces were then freeze-dried, extracted, and analyzed by HPLC. In one experiment, fresh feces of our mutagen excreter and nonexcreter were supplemented with the methanol extract; it was prepared in the same manner as for the fecal extract broths and added at the same concentration (100 mg of dry feces per ml).…”

Section: Methodsmentioning

confidence: 99%

Production of a fecal mutagen by Bacteroides spp

Tassel¹,

MacDonald²,

Wilkins³

1982

Infect Immun

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Forty species of anaerobes were screened for the ability to produce an etherextractable mutagen which is present in the feces of 15 to 20% of individuals in populations at high risk for colon cancer. This mutagen can be produced in vitro by incubating the feces of these individuals anaerobically or by supplementing anaerobic broths with methanol extracts of the feces and incubating them with a dilute fecal inoculum. Of the anaerobes screened, strains of five species of Bacteroides (B. thetaiotaomicron, B. fragilis, B. ovatus, B. uniformis, and Bacteroides group 3452A) were capable of producing fiveto eightfold increases in the concentration of mutagen. For in vitro production in broth, all producers required bile and the methanol extract for feces from a person who excretes the mutagen. Mutagen production appeared to be constitutive and occurred during the stationary phase of growth. Cell-free extracts were active and produced mutagen considerably faster than did whole cells. Our observations indicate that the excretion of this mutagen by certain people is dependent on the presence of some precursor of unknown origin. The mutagen-producing species of bacteria are among the most common of the intestinal microflora and were present in mutagen excreters and nonexcreters as well.

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Stimulation of mutagen production in human feces by bile and bile acids

Cited by 38 publications

References 9 publications

Role of bile acids in colorectal carcinogenesis

Role of bile acids in colorectal carcinogenesis

Fecal bile acid excretion and composition in response to changes in dietary wheat bran, fat and calcium in the rat

Production of a fecal mutagen by Bacteroides spp

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