Acta Pharmaceutica Sinica B (May 2022)
Aristolochic acids exposure was not the main cause of liver tumorigenesis in adulthood
- Shuzhen Chen,
- Yaping Dong,
- Xinming Qi,
- Qiqi Cao,
- Tao Luo,
- Zhaofang Bai,
- Huisi He,
- Zhecai Fan,
- Lingyan Xu,
- Guozhen Xing,
- Chunyu Wang,
- Zhichao Jin,
- Zhixuan Li,
- Lei Chen,
- Yishan Zhong,
- Jiao Wang,
- Jia Ge,
- Xiaohe Xiao,
- Xiuwu Bian,
- Wen Wen,
- Jin Ren,
- Hongyang Wang
Affiliations
- Shuzhen Chen
- National Center for Liver Cancer, Second Military Medical University, Shanghai 200438, China; International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
- Yaping Dong
- National Center for Liver Cancer, Second Military Medical University, Shanghai 200438, China; International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China; Fudan University Shanghai Cancer Center, Shanghai 200032, China; The Graduate School of Fujian Medical University, Fuzhou 350122, China
- Xinming Qi
- Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Qiqi Cao
- National Center for Liver Cancer, Second Military Medical University, Shanghai 200438, China; International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
- Tao Luo
- Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China; Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China
- Zhaofang Bai
- China Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
- Huisi He
- National Center for Liver Cancer, Second Military Medical University, Shanghai 200438, China; International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
- Zhecai Fan
- National Center for Liver Cancer, Second Military Medical University, Shanghai 200438, China; International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
- Lingyan Xu
- National Center for Liver Cancer, Second Military Medical University, Shanghai 200438, China; International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
- Guozhen Xing
- Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Chunyu Wang
- China Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
- Zhichao Jin
- Department of Health Statistics, Faculty of Medical Service, Second Military Medical University, Shanghai 200438, China
- Zhixuan Li
- National Center for Liver Cancer, Second Military Medical University, Shanghai 200438, China; International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
- Lei Chen
- National Center for Liver Cancer, Second Military Medical University, Shanghai 200438, China; International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
- Yishan Zhong
- National Center for Liver Cancer, Second Military Medical University, Shanghai 200438, China
- Jiao Wang
- Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China; Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China
- Jia Ge
- Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China; Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China
- Xiaohe Xiao
- China Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
- Xiuwu Bian
- Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China; Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China
- Wen Wen
- National Center for Liver Cancer, Second Military Medical University, Shanghai 200438, China; International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China; Corresponding authors. Tel.: +86 21 81875361, fax: +86 21 65566851 (Hongyang Wang); Tel.: +86 21 81875363; fax: +86 21 65566851 (Wen Wen)
- Jin Ren
- Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Corresponding authors. Tel.: +86 21 81875361, fax: +86 21 65566851 (Hongyang Wang); Tel.: +86 21 81875363; fax: +86 21 65566851 (Wen Wen)
- Hongyang Wang
- National Center for Liver Cancer, Second Military Medical University, Shanghai 200438, China; International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China; Fudan University Shanghai Cancer Center, Shanghai 200032, China; The Graduate School of Fujian Medical University, Fuzhou 350122, China; Corresponding authors. Tel.: +86 21 81875361, fax: +86 21 65566851 (Hongyang Wang); Tel.: +86 21 81875363; fax: +86 21 65566851 (Wen Wen)
- Journal volume & issue
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Vol. 12,
no. 5
pp. 2252 – 2267
Abstract
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.
