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粪便成分对大肠中粪卟啉动力学影响的体外研究

In vitro study on the effects of fecal composition on fecapentaene kinetics in the large bowel.

作者信息

de Kok T M, van Iersel M L, ten Hoor F, Kleinjans J C

机构信息

Department of Health Risk Analysis and Toxicology, University of Limburg, Maastricht, The Netherlands.

出版信息

Mutat Res. 1993 Jun;302(2):103-8. doi: 10.1016/0165-7992(93)90011-j.

DOI:10.1016/0165-7992(93)90011-j
PMID:7684504
Abstract

Dietary factors have been shown to affect excretion of fecapentaenes, potent mutagens present in human feces. Apart from effects of the diet on the bacterial synthesis of fecapentaenes in the bowel, fecapentaene excretion is likely to be indirectly influenced by the composition of the bowel contents, in particular fecapentaene-binding or -solubilizing factors. In the present study, interactions between dietary fiber and fecapentaene-12 (FP-12), as well as the effects of bile acids and calcium on the solubility of FP-12 in aqueous solutions, have been investigated in vitro. The results demonstrated that FP-12 may strongly adsorb to fiber, as indicated by reduced concentrations in the aqueous PBS phase when increasing amounts of fiber are added. This fecapentaene-binding capacity of fiber may explain the positive correlations that have previously been found between excreted fecapentaene concentrations and fiber consumption in human population studies. Further, it was found that at concentrations physiologically occurring in feces, both cholic and deoxycholic acid as well as mixtures of bile acids may increase the aqueous solubility of FP-12. This solubilizing effect of bile acids can be reduced by adding calcium at physiological concentrations of 2.5 mg/ml. It is hypothesized that high dietary fiber intake may increase fecapentaene excretion as a result of this fecapentaene fiber adsorption, which in turn may result in diminished exposure of the human bowel epithelium to these putative initiators of colorectal cancer. In contrast, high concentrations of fecal bile acids may act as fecapentaene-solubilizing factors which increase fecapentaene bioavailability, thereby possibly resulting in increased risk for colorectal cancer.

摘要

饮食因素已被证明会影响粪戊烯的排泄,粪戊烯是人类粪便中存在的强效诱变剂。除了饮食对肠道中粪戊烯细菌合成的影响外,粪戊烯的排泄可能还会受到肠内容物组成的间接影响,特别是粪戊烯结合或增溶因子。在本研究中,体外研究了膳食纤维与粪戊烯-12(FP-12)之间的相互作用,以及胆汁酸和钙对FP-12在水溶液中溶解度的影响。结果表明,随着添加纤维量的增加,水相PBS相中浓度降低,这表明FP-12可能会强烈吸附到纤维上。纤维的这种粪戊烯结合能力可以解释之前在人群研究中发现的排泄粪戊烯浓度与纤维摄入量之间的正相关关系。此外,研究发现,在粪便中生理浓度下,胆酸和脱氧胆酸以及胆汁酸混合物均可增加FP-12的水溶性。在2.5mg/ml的生理浓度下添加钙可降低胆汁酸的这种增溶作用。据推测,高膳食纤维摄入量可能会因这种粪戊烯纤维吸附作用而增加粪戊烯的排泄,这反过来可能会减少人类肠上皮细胞接触这些假定的结直肠癌引发剂的机会。相反,高浓度的粪便胆汁酸可能作为粪戊烯增溶因子,增加粪戊烯的生物利用度,从而可能导致结直肠癌风险增加。

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