Gut Microbial Transformation of the Dietary Imidazoquinoxaline Mutagen MelQx Reduces Its Cytotoxic and Mutagenic Potency
| Autor: | Christophe Lacroix, Michael T. Empl, Jianbo Zhang, Mostafa I. Fekry, Christina Engels, Shana J. Sturla, Clarissa Schwab, Mirjam Schneider, Pablo Steinberg |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Mutagen GUT MICROBIOME REDUCES TOXICITY OF MelQx Gut flora Toxicology medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Lactobacillus Quinoxalines medicine Animals Humans Carcinogen chemistry.chemical_classification Mice Inbred BALB C biology gut microbiota acrolein Spectrum Analysis Acrolein 3T3 Cells biology.organism_classification heterocyclic amines 3. Good health Lactobacillus reuteri Gastrointestinal Microbiome 030104 developmental biology chemistry Biochemistry dietary carcinogen 030220 oncology & carcinogenesis Heterocyclic amine Carcinogens metabolism Bacteria Mutagens |
| Zdroj: | Toxicological Sciences Toxicological Sciences, 159 (1) |
| ISSN: | 1096-6080 |
| Popis: | The diverse community of microbes present in the human gut has emerged as an important factor for cancer risk, potentially by altering exposure to chemical carcinogens. In the present study, human gut bacteria were tested for their capacity to transform the carcinogenic heterocyclic amine 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx). Eubacterium hallii, Lactobacillus reuteri, and Lactobacillus rossiae were able to convert MelQx to a new microbial metabolite characterized on the basis of high-resolution mass spectrometry and NMR as 9-hydroxyl-2,7-dimethyl-7,9,10,11-tetrahydropyrimido[2′,1′:2,3]imidazo[4,5-f]quinoxaline (MelQx-M1), resulting from conjugation with activated glycerol. Acrolein derived from the decomposition of 3-hydroxypropionaldehyde, which is the product of bacterial glycerol/diol dehydratase activity, was identified as the active compound responsible for the formation of MelQx-M1. A complex human gut microbial community obtained from invitro continuous intestinal fermentation was found to also transform MelQx to MelQx-M1. MelQx-M1 had slightly reduced cytotoxic potency toward human colon epithelial cells invitro, and diminished mutagenic potential toward bacteria after metabolic activation. As bacterially derived acrolein also transformed 2 other HCAs, namely 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3-methylimidazo[4,5-f]quinoline, these results generalize the capacity of gut microbiota to detoxify HCAs in the gut, potentially modulating cancer risk. ISSN:1096-6080 ISSN:1096-0929 |
| Databáze: | OpenAIRE |
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