Reen Rashmeet K, Nines Ron, Stoner Gary D
Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, Columbus 43210, USA.
Nutr Cancer. 2006;54(1):47-57. 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.
饮食冻干黑莓（BRB）可抑制N-亚硝基甲基苄胺（NMBA）诱导的Fischer 344大鼠食管肿瘤发生。为确定BRB抗启动作用的机制基础，在食管外植体培养物以及取自喂食AIN-76A饮食或含5%或10% BRB的AIN-76A饮食的大鼠的肝微粒体中研究了NMBA代谢。饮食中5%和10%的BRB抑制外植体（分别为26%和20%）和微粒体（分别为22%和28%）中的NMBA代谢，但这种抑制不呈剂量依赖性。为鉴定BRB中的活性抑制成分，用BRB的乙醇提取物或BRB的单个成分[鞣花酸（EA）和两种花青素（矢车菊素-3-葡萄糖苷和矢车菊素-3-芸香糖苷）]体外处理对照大鼠的食管外植体和肝微粒体。外植体中NMBA代谢受矢车菊素-3-芸香糖苷抑制最大（47%），其次是EA（33%）、矢车菊素-3-葡萄糖苷（23%）和提取物（即乙醇提取物，11%）。同样，在肝微粒体中，矢车菊素-3-芸香糖苷抑制作用最大（47%），其次是EA（33%）和矢车菊素-3-葡萄糖苷（32%）。苯乙基异硫氰酸酯（PEITC）是大鼠食管中NMBA肿瘤发生的有效抑制剂，在体内和体外比BRB或其成分更能有效抑制NMBA代谢。饮食BRB和PEITC可诱导肝脏中的谷胱甘肽S-转移酶活性。
