Blood Pyrrole-DNA Adducts Define the Early Tumorigenic Risk in Patients with Pyrrolizidine Alkaloid-Induced Liver Injury
文献类型：期刊论文
| 作者 | He, Yisheng1; Zhang, Wei2; Ma, Jiang1; Xia, Qingsu3; Song, Zijing1; Zhu, Lin1; Zhang, Chunyuan1; Liu, Jia4 ; Ye, Yang4; Fu, Peter P.3
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| 刊名 | ENVIRONMENTAL SCIENCE & TECHNOLOGY LETTERS
 |
| 出版日期 | 2021-07-13 |
| 卷号 | 8期号:7页码:551-557 |
| ISSN号 | 2328-8930 |
| DOI | 10.1021/acs.estlett.1c00359 |
| 通讯作者 | Zhuge, Yuzheng(yuzheng9111963@aliyun.com) ; Lin, Ge(linge@cuhk.edu.hk) |
| 英文摘要 | Pyrrolizidine alkaloids (PAs) are among the most common phytotoxins with emerging evidence to contaminate soil, water, and nearby plants. Humans are frequently exposed to PA-contaminated food products or PA-containing herbal remedies. The reactive metabolites of PAs rapidly alkylate DNA to form pyrrole-DNA adducts (PDAs) and seed a population of mutations that initiate tumorigenesis in experimental models. However, the clinical evidence of PA-induced initial DNA damage is absent. This study developed a liquid biopsy approach for detecting PDAs in blood to diagnose PA-induced genotoxicity. Blood DNA samples, extracted from PA-exposed rats, were reacted with silver nitrate to cleave the N-linkage between conjugated DNA bases and pyrrole. The released pyrrole was chemically derivatized to a stable product which was measured by liquid chromatography-tandem mass spectrometry. Using this method, PDAs were, for the first time, detected in blood samples from 18 patients with PA-induced liver injury. Notably, PDAs were detectable in patients blood samples collected one month after hospital admission, indicating adequate persistence of PDAs for use as a clinical biomarker of PA-induced genotoxicity. Our findings provide clinical indication of PA-induced genotoxicity, which warrants early detection of PDAs as an actionable approach for prevention of PA-associated carcinogenesis. |
| WOS关键词 | HEPATIC VENOOCCLUSIVE DISEASE ; BIOMARKER |
| 资助项目 | Research Grant Council of Hong Kong SAR[14107719] |
| WOS研究方向 | Engineering ; Environmental Sciences & Ecology |
| 语种 | 英语 |
| 出版者 | AMER CHEMICAL SOC |
| WOS记录号 | WOS:000674277000011 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/296701]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhuge, Yuzheng; Lin, Ge |
| 作者单位 | 1.Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Hong Kong 999077, Peoples R China 2.Nanjing Univ, Dept Gastroenterol, Affiliated Hosp, Sch Med, Nanjing 210008, Peoples R China 3.US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | He, Yisheng,Zhang, Wei,Ma, Jiang,et al. Blood Pyrrole-DNA Adducts Define the Early Tumorigenic Risk in Patients with Pyrrolizidine Alkaloid-Induced Liver Injury[J]. ENVIRONMENTAL SCIENCE & TECHNOLOGY LETTERS,2021,8(7):551-557. |
| APA | He, Yisheng.,Zhang, Wei.,Ma, Jiang.,Xia, Qingsu.,Song, Zijing.,...&Lin, Ge.(2021).Blood Pyrrole-DNA Adducts Define the Early Tumorigenic Risk in Patients with Pyrrolizidine Alkaloid-Induced Liver Injury.ENVIRONMENTAL SCIENCE & TECHNOLOGY LETTERS,8(7),551-557. |
| MLA | He, Yisheng,et al."Blood Pyrrole-DNA Adducts Define the Early Tumorigenic Risk in Patients with Pyrrolizidine Alkaloid-Induced Liver Injury".ENVIRONMENTAL SCIENCE & TECHNOLOGY LETTERS 8.7(2021):551-557. |
入库方式： OAI收割
来源：上海药物研究所
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