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Aristolochic acids exposure was not the main cause of liver tumorigenesis in adulthood

文献类型：期刊论文

作者Chen, Shuzhen8,9; Dong, Yaping5,6,8,9; Qi, Xinming7; Cao, Qiqi8,9; Luo, Tao3,4; Bai, Zhaofang2; He, Huisi8,9; Fan, Zhecai8,9; Xu, Lingyan8,9; Xing, Guozhen7
刊名ACTA PHARMACEUTICA SINICA B
出版日期2022-05-01
卷号12期号:5页码:2252-2267
ISSN号2211-3835
关键词Aristolochic acids (AAs) Mutational signature AA-DNA adduct Hepatocellular carcinoma (HCC) Liver tumorigenesis Hepatitis B virus (HBV) Risk factors Tumor prevention
DOI10.1016/j.apsb.2021.11.0112211-3835
通讯作者Wen, Wen(wenwen_smmu@163.com) ; Ren, Jin(jren@cdser.simm.ac.cn) ; Wang, Hongyang(hywangk@vip.sina.com)
英文摘要Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood. ?? 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
WOS关键词ARISTOLACTAM-DNA ADDUCTS ; CELL-PROLIFERATION ; MOUSE-LIVER ; TISSUES ; MUTAGENICITY ; PATHOGENESIS ; PERSISTENCE ; FIBROSIS ; GENE
资助项目Shanghai Key Laboratory of Hepatobiliary Tumor Biology ; National Major Scientific and Technological Special Project for Significant New Drugs Development (China)[2018ZX09101002] ; National Major Scientific and Technological Special Project for Significant New Drugs Development (China)[2018ZX09101002-001-001] ; National Major Scientific and Technological Special Project for Significant New Drugs Development (China)[2018ZX09101002-001-002] ; National Natural Science Foundation of China[81830054] ; National Natural Science Foundation of China[91859205] ; National Natural Science Foundation of China[81988101] ; National Natural Science Foundation of China[81722034] ; National Natural Science Foundation of China[81802878] ; Shanghai Pujiang Program (China)[2019PJD059] ; Shanghai Sailing Program (China)[18YF1400200] ; Key Discipline Project of Shanghai Municipal Education Commission (China)[201901070007E00065] ; Ministry of Education Key Laboratory on Signaling Regulation and Military Key Laboratory and Targeting Therapy of Liver Cancer, Second Military Medical University, Shanghai, China
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
WOS记录号WOS:000810889400008
源URL[http://119.78.100.183/handle/2S10ELR8/301714]  
专题新药研究国家重点实验室
通讯作者Wen, Wen; Ren, Jin; Wang, Hongyang
作者单位1.Second Mil Med Univ, Fac Med Serv, Dept Hlth Stat, Shanghai 200438, Peoples R China
2.Chinese Peoples Liberat Army Gen Hosp, China Mil Inst Chinese Mat, Med Ctr 5, Beijing 100039, Peoples R China
3.Minist Educ China, Key Lab Tumor Immunopathol, Chongqing 400038, Peoples R China
4.Third Mil Med Univ, Southwest Hosp, Inst Pathol, Army Med Univ, Chongqing 400038, Peoples R China
5.Fujian Med Univ, Grad Sch, Fuzhou 350122, Peoples R China
6.Fudan Univ, Shanghai Canc Ctr, Shanghai 200032, Peoples R China
7.Chinese Acad Sci, Ctr Drug Safety Evaluat & Res, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
8.Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Int Cooperat Lab Signal Transduct, Shanghai 200438, Peoples R China
9.Second Mil Med Univ, Natl Ctr Liver Canc, Shanghai 200438, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Shuzhen,Dong, Yaping,Qi, Xinming,et al. Aristolochic acids exposure was not the main cause of liver tumorigenesis in adulthood[J]. ACTA PHARMACEUTICA SINICA B,2022,12(5):2252-2267.
APA Chen, Shuzhen.,Dong, Yaping.,Qi, Xinming.,Cao, Qiqi.,Luo, Tao.,...&Wang, Hongyang.(2022).Aristolochic acids exposure was not the main cause of liver tumorigenesis in adulthood.ACTA PHARMACEUTICA SINICA B,12(5),2252-2267.
MLA Chen, Shuzhen,et al."Aristolochic acids exposure was not the main cause of liver tumorigenesis in adulthood".ACTA PHARMACEUTICA SINICA B 12.5(2022):2252-2267.

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来源：上海药物研究所

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