Aristolochic acid I promoted clonal expansion but did not induce hepatocellular carcinoma in adult rats
文献类型：期刊论文
| 作者 | Liu, Yong-zhen1,2 ; Lu, Heng-lei1,2; Qi, Xin-ming2; Xing, Guo-zhen2; Wang, Xin2; Yu, Pan2; Liu, Lu2; Yang, Fang-fang2; Ding, Xiao-lan2; Zhang, Ze-an1
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2021-03-08 |
| 页码 | 12 |
| 关键词 | aristolochic acid I glutathione S-transferase placental form-positive foci clonal expansion hepatocellular carcinoma medium-term rat liver bioassay DNA adducts |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/s41401-021-00622-7 |
| 通讯作者 | Deng, Zhong-ping(dzp@shutcm.edu.cn) ; Gong, Li-kun(lkgong@cdser.simm.ac.cn) ; Ren, Jin(jren@cdser.simm.ac.cn) |
| 英文摘要 | Aristolochic acid I (AAI) is a well-known nephrotoxic carcinogen, which is currently reported to be also associated with hepatocellular carcinoma (HCC). Whether AAI is a direct hepatocarcinogen remains controversial. In this study we investigated the association between AAI exposure and HCC in adult rats using a sensitive rat liver bioassay with several cofactors. Formation of glutathione S-transferase placental form-positive (GST-P+) foci was used as the marker for preneoplastic lesions/clonal expansion. We first conducted a medium-term (8 weeks) study to investigate whether AAI had any tumor-initiating or -promoting activity. Then a long-term (52 weeks) study was conducted to determine whether AAI can directly induce HCC. We showed that oral administration of single dose of AAI (20, 50, or 100 mg/kg) in combination with partial hepatectomy (PH) to stimulate liver proliferation did not induce typical GST-P+ foci in liver. In the 8-week study, only high dose of AAI (10 mg center dot kg(-1) center dot d(-1), 5 days a week for 6 weeks) in combination with PH significantly increased the number and area of GST-P+ foci initiated by diethylnitrosamine (DEN) in liver. Similarly, only high dose of AAI (10 mg center dot kg(-1)center dot d(-1), 5 days a week for 52 weeks) in combination with PH significantly increased the number and area of hepatic GST-P+ foci in the 52-week study. No any nodules or HCC were observed in liver of any AAI-treated groups. In contrast, long-term administration of AAI (0.1, 1, 10 mg center dot kg(-1)center dot d(-1)) time- and dose-dependently caused death due to the occurrence of cancers in the forestomach, intestine, and/or kidney. Besides, AAI-DNA adducts accumulated in the forestomach, kidney, and liver in a time- and dose-dependent manner. Taken together, AAI promotes clonal expansion only in the high-dose group but did not induce any nodules or HCC in liver of adult rats till their deaths caused by cancers developed in the forestomach, intestine, and/or kidney. Findings from our animal studies will pave the way for further large-scale epidemiological investigation of the associations between AA and HCC. |
| 资助项目 | National Science and Technology Major Project[2018ZX09101002-002] ; National Science and Technology Major Project[2018ZX09201017-004] ; National Science and Technology Major Project[2012ZX09301] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000626442900001 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/295424]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Deng, Zhong-ping; Gong, Li-kun; Ren, Jin |
| 作者单位 | 1.Shanghai Univ Tradit Chinese Med, Innovat Res Inst Tradit Chinese Med, Ctr Drug Safety Evaluat & Res, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Inst Drug Discovery & Dev, Zhongshan 528400, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Yong-zhen,Lu, Heng-lei,Qi, Xin-ming,et al. Aristolochic acid I promoted clonal expansion but did not induce hepatocellular carcinoma in adult rats[J]. ACTA PHARMACOLOGICA SINICA,2021:12. |
| APA | Liu, Yong-zhen.,Lu, Heng-lei.,Qi, Xin-ming.,Xing, Guo-zhen.,Wang, Xin.,...&Ren, Jin.(2021).Aristolochic acid I promoted clonal expansion but did not induce hepatocellular carcinoma in adult rats.ACTA PHARMACOLOGICA SINICA,12. |
| MLA | Liu, Yong-zhen,et al."Aristolochic acid I promoted clonal expansion but did not induce hepatocellular carcinoma in adult rats".ACTA PHARMACOLOGICA SINICA (2021):12. |
入库方式： OAI收割
来源：上海药物研究所
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