The microbial PhIP metabolite 7-hydroxy-5-methyl-3-phenyl-6,7,8,9-tetrahydropyrido[3′,2′:4,5]imidazo[1,2-a]pyrimidin-5-ium chloride (PhIP-M1) induces DNA damage, apoptosis and cell cycle arrest towards Caco-2 cells

Vanhaecke, Lynn; Derycke, Lara; Curieux, Frank Le; Lust, Sofie; Marzin, Daniel; Verstraete, Willy; Bracke, Marc

doi:10.1016/j.toxlet.2008.02.004

Cited by 23 publications

(13 citation statements)

References 44 publications

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“…The mutagenic potency of PhIP‐M1 in the Ames test was only 5% that of PhIP, and the adverse response was speculated to be attributable to residual PhIP (Vanhaecke et al ., ). At and below 50 μM, PhIP‐M1 did not significantly damage DNA in Caco‐2 cells (Vanhaecke et al ., ). Additionally, PhIP‐M1 did not induce the malignant transformation of BALB/c 3T3 cells at concentrations of up to 25 μM (Nicken et al ., ) and did not alter cell viability at concentrations up to 10 μM (Vanhaecke et al ., ; Nicken et al ., ).…”

Section: Resultsmentioning

confidence: 97%

“…At and below 50 μM, PhIP‐M1 did not significantly damage DNA in Caco‐2 cells (Vanhaecke et al ., ). Additionally, PhIP‐M1 did not induce the malignant transformation of BALB/c 3T3 cells at concentrations of up to 25 μM (Nicken et al ., ) and did not alter cell viability at concentrations up to 10 μM (Vanhaecke et al ., ; Nicken et al ., ). In the context of the findings reported in this study, these data suggest that the E. hallii ‐mediated transformation of PhIP to PhIP‐M1 is a detoxification process.…”

Section: Resultsmentioning

confidence: 97%

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The strict anaerobic gut microbe Eubacterium hallii transforms the carcinogenic dietary heterocyclic amine 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP)

Fekry

Engels

Zhang

et al. 2016

Environ Microbiol Rep

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2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) is the most abundant food-derived heterocyclic aromatic amine in well-cooked meats and may contribute to the recognized carcinogenicity of processed meats. In this study, a panel of human gut microbes was tested for their ability to convert PhIP to a conjugate PhIP-M1. Eubacterium hallii was newly identified to catalyse the conversion of PhIP to PhIP-M1 with high efficiency. The reaction was shown to involve the metabolism of glycerol to 3-hydroxypropionaldehyde as a key pathway. The proficiency of E. hallii in transforming PhIP in the presence of a complex intestinal microbiota was confirmed using batch fermentations inoculated with effluents from a continuous intestinal fermentation model mimicking human proximal and distal colon microbiota. In batch fermentations inoculated with proximal colon microbiota, PhIP-M1 transformation corresponded to an up to 300-fold increase of E. hallii. In contrast, PhIP transformation of distal colon microbiota was low but increased by 120-fold after supplementation with E. hallii. These findings indicate for the first time the relevance of the abundant commensal strict anaerobe E. hallii in the transformation of a dietary carcinogen that could contribute to its detoxification in the human colon.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 97%

The strict anaerobic gut microbe Eubacterium hallii transforms the carcinogenic dietary heterocyclic amine 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP)

Fekry

Engels

Zhang

et al. 2016

Environ Microbiol Rep

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“…This chemical pathway is effectively blocked by conjugation of HCAs with acrolein, which could lead to a natural detoxification step. Therefore, intestinal glycerol metabolism to 3-HPA and acrolein might establish a basis on how microbial communities may mitigate HCA or induce acrolein exposure256061.…”

Section: Discussionmentioning

confidence: 99%

Acrolein contributes strongly to antimicrobial and heterocyclic amine transformation activities of reuterin

Engels

Schwab

Zhang³

et al. 2016

Sci Rep

105

145

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Glycerol/diol dehydratases catalyze the conversion of glycerol to 3-hydroxypropionaldehyde (3-HPA), the basis of a multi-component system called reuterin. Reuterin has antimicrobial properties and undergoes chemical conjugation with dietary heterocyclic amines (HCAs). In aqueous solution reuterin is in dynamic equilibrium with the toxicant acrolein. It was the aim of this study to investigate the extent of acrolein formation at various physiological conditions and to determine its role in biological and chemical activities. The application of a combined novel analytical approach including IC-PAD, LC-MS and NMR together with specific acrolein scavengers suggested for the first time that acrolein, and not 3-HPA, is the active compound responsible for HCA conjugation and antimicrobial activity attributed to reuterin. As formation of the HCA conjugate was observed in vivo, our results imply that acrolein is formed in the human gut with implications on detoxification of HCAs. We propose to re-define the term reuterin to include acrolein.

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“…PhIP‐M1 induced apoptosis and significantly increased DNA damage in Caco‐2 cells, as quantified by the alkaline comet assay and it was dose dependent (in the range of 50–200 μM). PhIP‐M1 was more cyto‐ and genotoxic, than PhIP at the similar dose (Vanhaecke et al. 2008).…”

Section: Discussionmentioning

confidence: 99%

Effect of probiotic lactobacilli on faecal enzyme and genotoxic activity in human faecal water in the presence of the carcinogen PhIP in vitro

Nowak

Śliżewska

Klewicka

2011

Int J of Dairy Tech

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The average β‐glucuronidase activity for children was 0.48 ± 0.04 U/mg, for adults 0.75 ± 0.27 U/mg and for elderly 1.55 ± 0.06 U/mg. For β‐glucosidase, it was 0.19 ± 0.02 U/mg for children, 0.77 ± 0.26 U/mg for adults and 1.18 ± 0.27 U/mg for elderly. In the presence of probiotics, the highest decrease in genotoxicity was observed for Lactobacillus casei 0908 (to 7.99 ± 1.32) and Lactobacillus paracasei 0919 (to 6.19 ± 1.44) for all children. In adults, lower mean genotoxicity was regarded after incubation of PhIP with L. casei 0908 (it was 5.27 ± 1.13) and L. paracasei 0919 (it was o 6.01 ± 1.00). For elderly, statistically significant decrease was maintained after incubation of PhIP with L. casei 0900 (to 6.72 ± 2.67).

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The microbial PhIP metabolite 7-hydroxy-5-methyl-3-phenyl-6,7,8,9-tetrahydropyrido[3′,2′:4,5]imidazo[1,2-a]pyrimidin-5-ium chloride (PhIP-M1) induces DNA damage, apoptosis and cell cycle arrest towards Caco-2 cells

Cited by 23 publications

References 44 publications

The strict anaerobic gut microbe Eubacterium hallii transforms the carcinogenic dietary heterocyclic amine 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP)

The strict anaerobic gut microbe Eubacterium hallii transforms the carcinogenic dietary heterocyclic amine 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP)

Acrolein contributes strongly to antimicrobial and heterocyclic amine transformation activities of reuterin

Effect of probiotic lactobacilli on faecal enzyme and genotoxic activity in human faecal water in the presence of the carcinogen PhIP in vitro

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