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    Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/2226


    Title: Metabolic Activation of the Tumorigenic Pyrrolizidine Alkaloid, Riddelliine, Leading to DNAAdduct Formation in Vivo
    Authors: Ya-Chen Yang;Jian Yan;Daniel R. Doerge;Po-Cheun Chan;Peter P. Fu;MingW.Chou
    Contributors: 保健營養生技學系
    Date: 2001
    Issue Date: 2009-10-29 07:21:12 (UTC+0)
    Abstract: Riddelliine is a representative naturally occurring genotoxic pyrrolizidine alkaloid. We have studied the mechanism by which riddelliine induces hepatocellular tumors in vivo. Metabolism of riddelliine by liver microsomes of F344 female rats generated riddelliine N-oxide and dehydroretronecine (DHR) as major metabolites. Metabolism was enhanced when liver microsomes from phenobarbital-treated rats were used. Metabolism in the presence of calf thymus DNA resulted in eight DNA adducts that were identical to those obtained from the reaction of DHR with calf thymus DNA. Two of these adducts were identified as DHR-modified 7-deoxyguanosin-N2-yl epimers (DHR−3‘-dGMP); the other six were DHR-derived DNA adducts, but their structures were not characterized. A similar DNA adduct profile was detected in the livers of female F344 rats fed riddelliine, and a dose−response relationship was obtained for the level of the total (eight) DHR-derived DNA adducts and the level of the DHR−3‘-dGMP adducts. These results suggest that riddelliine induces liver tumors in rats through a genotoxic mechanism and the eight DHR-derived DNA adducts are likely to contribute to liver tumor development.
    Relation: Chemical Research in Toxicology 14 (1):101–109
    Appears in Collections:[Department of Food Nutrition and Healthy Biotechnology] Journal Article

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