The long persistence of pyrrolizidine alkaloid-derived DNA adducts in vivo: kinetic study following single and multiple exposures in male ICR mice
文献类型：期刊论文
| 作者 | Zhu, Lin2; Xue, Junyi2; Xia, Qingsu3; Fu, Peter P1; Lin, Ge2 |
| 刊名 | Archives of toxicology
 |
| 出版日期 | 2017-02 |
| 卷号 | 91期号:2页码:949-965 |
| ISSN号 | 1432-0738 |
| DOI | 10.1007/s00204-016-1713-z |
| 文献子类 | Article |
| 英文摘要 | Pyrrolizidine alkaloid (PA)-containing plants are widespread in the world and the most common poisonous plants affecting livestock, wildlife, and humans. Our previous studies demonstrated that PA-derived DNA adducts can potentially be a common biological biomarker of PA-induced liver tumor formation. In order to validate the use of these PA-derived DNA adducts as a biomarker, it is necessary to understand the basic kinetics of the PA-derived DNA adducts formed in vivo. In this study, we studied the dose-dependent response and kinetics of PA-derived DNA adduct formation and removal in male ICR mice orally administered with a single dose (40 mg/kg) or multiple doses (10 mg/kg/day) of retrorsine, a representative carcinogenic PA. In the single-dose exposure, the PA-derived DNA adducts exhibited dose-dependent linearity and persisted for up to 4 weeks. The removal of the adducts following a single-dose exposure to retrorsine was biphasic with half-lives of 9 h (t ) and 301 h (~12.5 days, t ). In the 8-week multiple exposure study, a marked accumulation of PA-derived DNA adducts without attaining a steady state was observed. The removal of adducts after the multiple exposure also demonstrated a biphasic pattern but with much extended half-lives of 176 h (~7.33 days, t ) and 1736 h (~72.3 days, t ). The lifetime of PA-derived DNA adducts was more than 8 weeks following the multiple-dose treatment. The significant persistence of PA-derived DNA adducts in vivo supports their role in serving as a biomarker of PA exposure. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/266832]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Fu, Peter P; Lin, Ge |
| 作者单位 | 1.National Center for Toxicological Research, Jefferson, AR, 72079, USA. peter 2.School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China; 3.National Center for Toxicological Research, Jefferson, AR, 72079, USA; |
| 推荐引用方式 GB/T 7714 | Zhu, Lin,Xue, Junyi,Xia, Qingsu,et al. The long persistence of pyrrolizidine alkaloid-derived DNA adducts in vivo: kinetic study following single and multiple exposures in male ICR mice[J]. Archives of toxicology,2017,91(2):949-965. |
| APA | Zhu, Lin,Xue, Junyi,Xia, Qingsu,Fu, Peter P,&Lin, Ge.(2017).The long persistence of pyrrolizidine alkaloid-derived DNA adducts in vivo: kinetic study following single and multiple exposures in male ICR mice.Archives of toxicology,91(2),949-965. |
| MLA | Zhu, Lin,et al."The long persistence of pyrrolizidine alkaloid-derived DNA adducts in vivo: kinetic study following single and multiple exposures in male ICR mice".Archives of toxicology 91.2(2017):949-965. |
入库方式： OAI收割
来源：上海药物研究所
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