ASIA unversity:Item 310904400/2223
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    题名: Detection of Riddelliine-Derived DNA Adducts in Blood of Rats Fed Riddelliine
    作者: Jian Yan;Jasyl Nichols;Ya-Chen Yang;Peter P. Fu;MingW. Chou
    贡献者: 保健營養生技學系
    关键词: Pyrrolizidine alkaloids;riddelliine;dehydroretronecine;32P-postlabeling/HPLC;rat blood DNA adducts
    日期: 2002
    上传时间: 2009-10-28 09:28:39 (UTC+0)
    摘要: We have previously shown that riddelliine, a naturally occurring genotoxic pyrrolizidine alkaloid, induces liver tumors in rats and mice through a genotoxic mechanism mediated by the formation of a set of eight 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5Hpyrrolizine ( DHP)-derived DNA adducts. In this study we report the formation of these DHP-derived DNA adducts in blood DNA of rats fed riddelliine. In an adduct formation and removal experiment, male and female F344 rats (8 weeks of age) were administered riddelliine by gavage at a single dose of 10.0 mg/kg body weight in 0.1 M phosphate buffer. At 8, 24, 48, and 168 hrs after dosing, the levels of DHP-derived DNA adduct in blood and liver were determined by 32P-postlabeling/HPLC. Maximum DNA adduct formation occurred at 48 hr after treatment. From 48 to 168 hours, the adduct levels in female rat blood were 4-fold greater than those in male rats. In a dose response experiment, female rats were gavaged 0.1 and 1.0 mg/kg doses of riddelliine for three consecutive days and the DHPderived DNA adducts in blood DNA were assayed. The levels of the DHP-derived DNA adducts in blood of rats receiving 0.1 and 1.0 mg/kg doses were 12.9 and 51.8 adducts/107 nucleotides. These results suggest that: (i) leucocyte DNA can bind with DHP to form a set of DHP-derived DNA adducts generated in liver; (ii) DHP-derived DNA adducts in blood can serve as a potential non-invasive biomarkers for assessing the exposure to riddelliine.
    關聯: International Journal of Molecular Sciences
    显示于类别:[食品營養與保健生技學系] 期刊論文

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