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倒千里光碱(一种吡咯里西啶生物碱)对培养的人肝细胞的影响。

The effect of heliotrine, a pyrrolizidine alkaloid, on human liver cells in culture.

作者信息

Sullman S F, Zuckerman A J

出版信息

Br J Exp Pathol. 1969 Aug;50(4):361-70.

PMID:5806426
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2072115/
Abstract

The effects of heliotrine on human embryo hepatocytes in culture and on cells of a continuous cell line derived from human liver were investigated. Cell necrosis did not occur but cytological changes consisting mainly of cytoplasmic vacuolation were produced in the hepatocytes. Progressive hypertrophy of the hepatocytes and of cells of the continuous line was observed. The enlargement of the cells increased both with the concentration and the period of exposure to the alkaloid. Heliotrine inhibited the synthesis of nucleic acids and protein by all the cell types present in primary cultures of the liver. The experimental data indicated that the action of heliotrine was primarily on the synthesis of DNA but some inhibition of RNA synthesis also occurred. It is proposed that heliotrine acts mainly in the major groove of the DNA helix inhibiting the DNA polymerase but there is also an effect on the RNA polymerase in the minor groove. The mechanism of action of heliotrine could be similar to the action of some of the antibiotics, in particular aflatoxin B.

摘要

研究了天芥菜碱对培养的人胚胎肝细胞以及源自人肝脏的连续细胞系细胞的影响。未发生细胞坏死,但肝细胞出现了主要由细胞质空泡化组成的细胞学变化。观察到肝细胞和连续细胞系的细胞逐渐肥大。细胞的增大随生物碱的浓度和暴露时间而增加。天芥菜碱抑制肝脏原代培养物中所有细胞类型的核酸和蛋白质合成。实验数据表明,天芥菜碱的作用主要作用于DNA合成,但也发生了对RNA合成的一些抑制。有人提出,天芥菜碱主要作用于DNA螺旋的大沟,抑制DNA聚合酶,但对小沟中的RNA聚合酶也有影响。天芥菜碱的作用机制可能类似于某些抗生素,特别是黄曲霉毒素B的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1129/2072115/6754760bdc36/brjexppathol00436-0046-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1129/2072115/9fa38daab318/brjexppathol00436-0047-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1129/2072115/6754760bdc36/brjexppathol00436-0046-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1129/2072115/9fa38daab318/brjexppathol00436-0047-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1129/2072115/6754760bdc36/brjexppathol00436-0046-a.jpg

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The effect of heliotrine, a pyrrolizidine alkaloid, on human liver cells in culture.倒千里光碱(一种吡咯里西啶生物碱)对培养的人肝细胞的影响。
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本文引用的文献

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Primary liver tumours in rats following feeding with alkaloids of Senecio jacobaea.用千里光生物碱喂养大鼠后出现的原发性肝肿瘤。
Br J Cancer. 1950 Dec;4(4):405-10. doi: 10.1038/bjc.1950.39.
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Further observations on the subacute and chronic liver changes in rats after a single dose of various pyrrolizidine (Senecio) alkaloids.关于大鼠单次给予各种吡咯里西啶(千里光)生物碱后亚急性和慢性肝脏变化的进一步观察
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Induction of morphological changes in human embryo liver cells by the pyrrolizidine alkaloid lasiocarpine.吡咯里西啶生物碱阔叶千里光碱对人胚胎肝细胞形态变化的诱导作用。
Br J Exp Pathol. 1972 Apr;53(2):145-9.
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Tissue culture of rat adult decapsulated adrenal glands. A methodological, ultrastructural and morphometric investigation.成年大鼠去包膜肾上腺的组织培养。一项方法学、超微结构和形态计量学研究。
Z Zellforsch Mikrosk Anat. 1972;135(2):245-73. doi: 10.1007/BF00315129.
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In vitro assay of cytotoxicity with cultured liver: accomplishments and possibilities.利用培养肝脏进行细胞毒性的体外测定:成果与前景
Environ Health Perspect. 1978 Aug;25:161-71. doi: 10.1289/ehp.7825161.
氰化物和叠氮化物对吡咯里西啶生物碱天芥菜碱在黑腹果蝇中致突变活性的影响。
Z Vererbungsl. 1963 Dec 30;94:331-5. doi: 10.1007/BF00897592.
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Alkylation as the mechanism by which the hepatotoxic pyrrolizidine alkaloids act on cell nuclei.烷基化是具有肝毒性的吡咯里西啶生物碱作用于细胞核的机制。
Nature. 1962 Aug 11;195:570-3. doi: 10.1038/195570a0.
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The chronic pathological effects on the liver of the rat of the pyrrolizidine alkaloids heliotrine, lasiocarpine, and their N-oxides.倒千里光碱、阔叶千里光碱及其N-氧化物对大鼠肝脏的慢性病理影响。
J Pathol Bacteriol. 1959 Oct;78:483-502. doi: 10.1002/path.1700780215.
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Senecio alkaloids; primary liver tumours in rats as a result of treatment with (1) a mixture of alkaloids from S. jacobaea Lin.; (2) retrorsine; (3) isatidine.千里光生物碱;大鼠原发性肝肿瘤,由以下物质处理所致:(1)来自欧洲千里光的生物碱混合物;(2)倒千里光碱;(3)异阿替丁。
Br J Cancer. 1954 Sep;8(3):458-65. doi: 10.1038/bjc.1954.49.
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The ultrastructure of the enlarged hepatocytes induced in rats with a single oral dose of retrorsine, a pyrrolizidine (Senecio) alkaloid.用单剂量口服倒千里光碱(一种吡咯里西啶(千里光属)生物碱)诱导大鼠产生的肿大肝细胞的超微结构。
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The interaction of aflatoxins with purines and purine nucleosides.黄曲霉毒素与嘌呤及嘌呤核苷的相互作用。
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Delayed hepatitis and cirrhosis in weanling rats following a single small dose of the senecio alkaloid, lasiocarpine.断奶大鼠单次小剂量服用千里光生物碱阔叶千里光碱后出现的迟发性肝炎和肝硬化
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Toxicity of pyrrolizidine alkaloids.吡咯里西啶生物碱的毒性
Nature. 1968 Feb 24;217(5130):723-8. doi: 10.1038/217723a0.