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马兜铃酸经口给药后可在大鼠的肝外组织中诱导产生6-硫鸟嘌呤抗性突变体。

Aristolochic acid induces 6-thioguanine-resistant mutants in an extrahepatic tissue in rats after oral application.

作者信息

Maier P, Schawalder H P, Weibel B, Zbinden G

出版信息

Mutat Res. 1985 Jul;143(3):143-8. doi: 10.1016/s0165-7992(85)80025-7.

DOI:10.1016/s0165-7992(85)80025-7
PMID:4010694
Abstract

The mutagenic activity of the natural plant product aristolochic acid (AA) was tested in the Granuloma Pouch Assay, which detects gene mutations induced in a subcutaneous granuloma tissue of rats. After direct exposure of the target tissue, AA induced high frequencies of mutants at a relatively low cytostatic/cytotoxic level. AA was more potent that N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at equimolar doses. After oral application of AA, a dose-dependent mutagenic activity was seen. In contrast a very weak and inconsistent mutagenic effect was seen after systemic application of MNNG. These observations suggest that after oral application AA is not detoxified efficiently and can exert its mutagenic activity in extrahepatic tissues whereas MNNG is detoxified to a large extent at the site of administration.

摘要

在肉芽肿袋试验中检测了天然植物产物马兜铃酸(AA)的致突变活性,该试验可检测大鼠皮下肉芽肿组织中诱导的基因突变。在直接暴露于靶组织后,AA在相对较低的细胞生长抑制/细胞毒性水平下诱导出高频率的突变体。在等摩尔剂量下,AA比N-甲基-N'-硝基-N-亚硝基胍(MNNG)更具效力。口服AA后,可见剂量依赖性致突变活性。相比之下,全身应用MNNG后可见非常微弱且不一致的致突变作用。这些观察结果表明,口服后AA不能有效解毒,可在肝外组织发挥其致突变活性,而MNNG在给药部位在很大程度上被解毒。

相似文献

1
Aristolochic acid induces 6-thioguanine-resistant mutants in an extrahepatic tissue in rats after oral application.马兜铃酸经口给药后可在大鼠的肝外组织中诱导产生6-硫鸟嘌呤抗性突变体。
Mutat Res. 1985 Jul;143(3):143-8. doi: 10.1016/s0165-7992(85)80025-7.
2
Evaluation of the DNA-damaging and mutagenic activity of oxolinic and pipemidic acids by the granuloma pouch assay.通过肉芽肿袋试验评估恶喹酸和吡哌酸的DNA损伤及诱变活性。
Mutagenesis. 1988 Sep;3(5):397-401. doi: 10.1093/mutage/3.5.397.
3
Granuloma pouch assay. II. Induction of 6-thioguanine resistance by MNNG and benzo[a]pyrene in vivo.肉芽肿袋试验。II. N-甲基-N'-硝基-N-亚硝基胍(MNNG)和苯并[a]芘在体内诱导6-硫代鸟嘌呤抗性。
Mutat Res. 1980 Feb;77(2):165-73. doi: 10.1016/0165-1218(80)90134-2.
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HGPRT- mutants of V79 cells that revert specifically by base pair substitution and frameshift mutations.V79细胞的次黄嘌呤鸟嘌呤磷酸核糖转移酶(HGPRT)突变体,其通过碱基对替换和移码突变进行特异性回复突变。
Environ Mutagen. 1985;7(3):281-91. doi: 10.1002/em.2860070305.
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Strand- and sequence-specific attenuation of N-methyl-N'-nitro-N-nitrosoguanidine-induced G.C to A.T transitions by expression of human 6-methylguanine-DNA methyltransferase in Chinese hamster ovary cells.在中国仓鼠卵巢细胞中,通过表达人6-甲基鸟嘌呤-DNA甲基转移酶对N-甲基-N'-硝基-N-亚硝基胍诱导的G.C到A.T转变进行链特异性和序列特异性衰减。
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Low oxygen tension, as found in tissues in vivo, alters the mutagenic activity of aristolochic acid I and II in primary fibroblast-like rat cells in vitro.
Environ Mol Mutagen. 1987;10(3):275-84. doi: 10.1002/em.2850100306.
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Mutagenicity testing in mammalian cells. II. Validation of multiple drug-resistance markers having practical application for screening potential mutagens.哺乳动物细胞中的致突变性检测。II. 对具有筛选潜在诱变剂实际应用价值的多种耐药标记物的验证。
Mutat Res. 1980 Sep;72(2):207-30. doi: 10.1016/0027-5107(80)90036-6.
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Induction of mutations by chemical agents at the hypoxanthine-guanine phosphoribosyl transferase locus in human epithelial teratoma cells.化学试剂在人上皮性畸胎瘤细胞次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶位点诱导突变
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Effect of O6-alkylguanine-DNA alkyltransferase on the frequency and spectrum of mutations induced by N-methyl-N'-nitro-N-nitrosoguanidine in the HPRT gene of diploid human fibroblasts.O6-烷基鸟嘌呤-DNA烷基转移酶对N-甲基-N'-硝基-N-亚硝基胍诱导二倍体人成纤维细胞HPRT基因的突变频率和谱的影响。
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Mutagenic effects at hprt locus and in minisatellite sequences induced in V79 cells by treatments with UV and methyl-nitro-nitroso guanidine.紫外线和甲基硝基亚硝基胍处理V79细胞后在次黄嘌呤磷酸核糖转移酶基因座和小卫星序列中诱导的诱变效应。
Mutat Res. 1995 Dec;348(4):193-9. doi: 10.1016/0165-7992(95)90009-8.

引用本文的文献

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Aristolochic Acid-Induced Genotoxicity and Toxicogenomic Changes in Rodents.马兜铃酸诱导的啮齿动物遗传毒性和毒理基因组变化
World J Tradit Chin Med. 2020 Jan-Mar;6(1):12-25. doi: 10.4103/wjtcm.wjtcm_33_19. Epub 2020 Mar 13.
2
Worldwide research trends on aristolochic acids (1957-2017): Suggestions for researchers.全球关于马兜铃酸(1957-2017)的研究趋势:对研究人员的建议。
PLoS One. 2019 May 2;14(5):e0216135. doi: 10.1371/journal.pone.0216135. eCollection 2019.
3
Aristolochic acid and 'Chinese herbs nephropathy': a review of the evidence to date.
马兜铃酸与“中草药肾病”:迄今证据综述
Drug Saf. 2003;26(1):33-48. doi: 10.2165/00002018-200326010-00004.