Bacterial Enzymes: Their Role in the Formation of Mutagens and Carcinogens in the Intestine

Mallett, A.K.; Rowland, I.R.

doi:10.1159/000171241

Cited by 19 publications

(10 citation statements)

References 36 publications

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“…Moreover, an increased transcellular permeability for lipophilic compounds in the terminal regions of the intestine might be compensated by enhanced P-gp levels [37]. Exposure of the colonic epithelium to carcinogenic compounds could also be higher due to bacterial metabolism [38] and lower transit rates demanding higher P-gp activity. In our mice study, it became evident that flavone also in vivo altered P-gp levels in all the intestinal segments but the impact was lower in vivo than in vitro with a maximal increase of about 1.6-fold in jejunum of mice whereas an almost three-fold increase in P-gp levels in Caco-2 cells was observed, respectively.…”

Section: Discussionmentioning

confidence: 99%

Flavonoids alter P‐gp expression in intestinal epithelial cells in vitro and in vivo

Lohner

Schnäbele

Daniel

et al. 2007

Molecular Nutrition Food Res

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Flavonoids are secondary plant metabolites included in our diet but are also provided in a growing number of supplements. They are suggested to interact with intestinal transport systems including phospho-glycoprotein (P-gp) which mediates the efflux of a variety of xenobiotics back into the gut lumen. In human intestinal Caco-2 cells, we tested the effects of 14 different flavonoids on P-gp expression in vitro. Protein expression levels were quantified by Western blotting, flow cytometry, and real-time PCR. Except apigenin, all flavonoids at concentrations of 10 microM increased P-gp expression in Western blotting experiments when cells were exposed to the compounds over 4 wk. Flavone was one of the most effective P-gp inducers in Caco-2 cells and its effects were, therefore, also assessed for changes in P-gp in vivo in the gastrointestinal tract of C57BL/6 mice. P-gp expression was significantly increased by flavone (400 mg/kg body weight x day over 4 wk) in the small intestine but not in the colon which displayed intrinsically the highest expression level. In conclusion, the increase in P-gp expression caused by flavonoids in intestinal epithelial cells in vitro and also in vivo may serve as an adaptation and defense mechanism limiting the entry of lipophilic xenobiotics into the organism.

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Section: Discussionmentioning

confidence: 99%

Flavonoids alter P‐gp expression in intestinal epithelial cells in vitro and in vivo

Lohner

Schnäbele

Daniel

et al. 2007

Molecular Nutrition Food Res

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“…With the capacity for the microflora to modulate colonic conditions, it becomes obvious why analysing their dynamic interaction with the colonic environment and mucosa is of such interest. The microflora has been implicated in the aetiology of CRC in a number of studies (reviewed in Mallett & Rowland, 1990) and these observations form the theoretical basis for use of gut flora biomarkers (faecal biomarkers). These biomarkers are advantageous as they can be assessed in faeces, which is readily accessible and non-invasive.…”

Section: Gut Flora-associated Biomarkersmentioning

confidence: 99%

Diet and cancer: assessing the risk

2002

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Globally, colorectal cancer (CRC) is a leading cause of mortality from malignant disease. Case–control and cohort studies provide strong support for a role of diet in the aetiology of CRC. However to establish causal relationships and to identify more precisely the dietary components involved, intervention studies in human subjects are required. Cancer is an impractical endpoint in terms of numbers, cost, study duration and ethical considerations. Consequently, intermediate biomarkers of the disease are required. This review aims to provide an overview of the intermediate endpoints available for the study of CRC, particularly non-invasive faecal biomarkers. Examples of their use in dietary intervention studies are given.

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“…We are unaware of any non-nutrient food constituents which influence this process. Mallett & Rowland (1990) have pointed out that bacteria present in the gut lumen express enzymes which may influence the metabolism of xenobiotics in host tissues. For instance, when potentially carcinogenic compounds are detoxified by UDPGT (Dutton, 1980) .…”

Section: U N J U B a I L U N B Y Y H A S C 11 E N L Y M Cmentioning

confidence: 99%