Metabolic Activation of the Tumorigenic Pyrrolizidine Alkaloid, Riddelliine, Leading to DNAAdduct Formation in Vivo

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题名:	Metabolic Activation of the Tumorigenic Pyrrolizidine Alkaloid, Riddelliine, Leading to DNAAdduct Formation in Vivo
作者:	Ya-Chen Yang;Jian Yan;Daniel R. Doerge;Po-Cheun Chan;Peter P. Fu;MingW.Chou
贡献者:	保健營養生技學系
日期:	2001
上传时间:	2009-10-29 07:21:12 (UTC+0)
摘要:	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.
關聯:	Chemical Research in Toxicology 14 (1):101–109
显示于类别:	[食品營養與保健生技學系] 期刊論文

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