Mutagenicity of arbutin in mammalian cells after activation by human intestinal bacteria

• Published in: Food and chemical toxicology Vol. 44; no. 11; pp. 1940 - 1947
• Main Authors: Blaut, Michael, Braune, Annett, Wunderlich, Sandra, Sauer, Patrick, Schneider, Heiko, Glatt, Hansruedi
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.11.2006; New York, NY Elsevier Science
• Subjects: Adult; Animals; Arbutin; Arbutin - classification; Arbutin - metabolism; Arbutin - toxicity; Bacteroides distasonis; beta-glucosidase; Bifidobacterium adolescentis; Biological and medical sciences; carcinogens; Cell Line; chemical composition; Chemical mutagenesis; classification; Cricetinae; Cricetulus; cytology; Cytosol; Cytosol - metabolism; dosage; dose response; Drug addictions; drug effects; Enterococcus casseliflavus; enzyme activity; Escherichia coli; Eubacterium ramulus; feces; Feces - microbiology; Female; Fibroblasts; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; Food-borne mutagens; gastric juice; Gastric Juice - microbiology; gastrointestinal system; genetics; glycosylation; Gram-Positive Bacteria; Gram-Positive Bacteria - drug effects; Gram-Positive Bacteria - metabolism; Humans; Hydroquinone; Hydroquinones; Hydroquinones - metabolism; Hypoxanthine Phosphoribosyltransferase; Hypoxanthine Phosphoribosyltransferase - genetics; Hypoxanthine Phosphoribosyltransferase - metabolism; Intestinal bacteria; intestinal crypts; intestinal microorganisms; Intestinal Mucosa; Intestinal Mucosa - microbiology; Intestines; Intestines - microbiology; Male; Medical sciences; metabolism; microbiology; mutagenicity; Mutagenicity Tests; Mutagens; Mutagens - classification; Mutagens - metabolism; Mutagens - toxicity; Plant Extracts; Plant Extracts - classification; Plant Extracts - metabolism; Plant Extracts - toxicity; plant-based foods; toxicity; Toxicology; β-Glucosidase; Hydroquinone; Intestinal bacteria; β-Glucosidase; Food-borne mutagens; HQ; Arbutin; 4-NPG; Human; Digestive system; Enzyme; Toxicity; Genotoxicity; Gut; Antioxidant; Mutagen; In vitro; Vertebrata; Mammalia; Glycosidases; Hydrolases; Bacteria; O-Glycosidases; Food
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2006.06.015

Arbutin (hydroquinone-β-D-glucopyranoside) is present in various food plants. Its aglycone, hydroquinone, is mutagenic and carcinogenic. We investigated whether hydroquinone may be released under conditions encountered in the human gastrointestinal tract. Arbutin was stable in artificial gastric juice. Fecal slurries from nine human subjects completely converted arbutin (2 mM) into hydroquinone. Four of nine representative human intestinal species investigated, namely Eubacterium ramulus, Enterococcus casseliflavus, Bacteroides distasonis, and Bifidobacterium adolescentis, deglycosylated arbutin at rates of 21.08, 16.62, 8.43 and 3.59 nmol × min −1 × (mg protein) −1, respectively. In contrast, homogenates from small intestinal mucosa and cytosolic fractions from colon mucosa deglycosylated arbutin at substantially lower rates: 0.50 and 0.09 nmol × min −1 × (mg protein) −1, respectively. Arbutin, unlike hydroquinone, did not induce gene mutations in Chinese hamster V79 cells in the absence of an activating system. However, in the presence of cytosolic fractions from E. ramulus or B. distasonis, arbutin was strongly mutagenic. Cytosolic fraction from Escherichia coli, showing no arbutin glycosidase activity, was not able to activate arbutin in this model system. The release of the proximate mutagen hydroquinone from arbutin by intestinal bacteria in the immediate vicinity of the colon mucosa may pose a potential risk.