Modulation of N-nitrosomethylbenzylamine metabolism by black raspberries in the esophagus and liver of Fischer 344 rats

• Published in: Nutrition and cancer Vol. 54; no. 1; pp. 47 - 57
• Main Authors: Reen, R.K, Nines, R, Stoner, G.D
• Format: Journal Article
• Language: English
• Published: United States Lawrence Erlbaum Associates, Inc 2006
• Subjects: animal disease models; Animals; anticarcinogenic activity; carcinogenesis; carcinogens; Carcinogens - metabolism; chemoprevention; Diet; Dimethylnitrosamine - analogs & derivatives; Dimethylnitrosamine - metabolism; dried fruit; enzyme activity; esophageal sphincter; Esophagus - drug effects; Esophagus - metabolism; freeze drying; Fruit - chemistry; glutathione transferase; Glutathione Transferase - metabolism; hydroxylation; Isothiocyanates - pharmacology; liver microsomes; Male; metabolism; Microsomes, Liver - drug effects; Microsomes, Liver - metabolism; nitrosamines; nutrition-genotype interaction; Organ Culture Techniques; oxidative stress; phytochemicals; raspberries; Rats; Rats, Inbred F344; Rosaceae - chemistry; Rubus occidentalis
• ISSN: 0163-5581; 1532-7914
• DOI: 10.1207/s15327914nc5401_6

Dietary freeze-dried black raspberries (BRBs) inhibit N-nitrosomethylbenzylamine (NMBA)-induced tumorigenesis in the Fischer 344 rat esophagus. To determine the mechanistic basis of the anti-initiating effects of BRBs, NMBA metabolism was studied in esophageal explant cultures and in liver microsomes taken from rats fed with AIN-76A diet or AIN-76A diet containing 5% or 10% BRBs. Five percent and 10% dietary BRBs inhibited NMBA metabolism in explants (26% and 20%) and in microsomes (22% and 28%), but the inhibition was not dose dependent. To identify active inhibitory component(s) in BRBs, esophageal explants and liver microsomes from control rats were treated in vitro with an ethanol extract of BRBs or with individual components of BRBs ellagic acid (EA) and two anthocyanins (cyanidin-3-glucoside and cyanidin-3-rutinoside). NMBA metabolism in explants was inhibited maximally by cyanidin-3-rutinoside (47%) followed by EA (33%), cyanidin-3-glucoside (23%), and the extract (11%). Similarly, in liver microsomes, the inhibition was maximal by cyanidin-3-rutinoside (47%) followed by EA (33%) and cyanidin-3-glucoside (32%). Phenylethylisothiocyanate (PEITC), a potent inhibitor of NMBA tumorigenesis in rat esophagus, was a stronger inhibitor of NMBA metabolism in vivo and in vitro than BRBs or their components. Dietary BRBs and PEITC induced glutathione S-transferase activity in the liver.