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体内3-甲基胆蒽代谢的气相色谱-质谱分析。

Gas chromatography-mass spectrometric analysis of 3-methyl-cholanthrene metabolism in vivo.

作者信息

Kinoshita K, Hashimoto K, Takahashi G, Yasuhira K

出版信息

Gan. 1980 Apr;71(2):181-9.

PMID:7202915
Abstract

Metabolites of 3-methylcholanthrene in tissues and excreta of rats and mice were extracted, directly or after removal from conjugation, with ethanol or ethyl acetate, purified by Sephadex LH-20 column chromatography, and examined by gas chromatography-mass spectrometric analysis. Data from the present experiments showed that the extracts after chromatographic purification were contaminated with some tissue-derived sterols such as cholesterol. As compounds related to 3-methylcholanthrene, a dehydro compound, 1- and 2-hydroxy compounds, 11-phenol and two other phenols were identified in the extracts. Some Ketones and cis-1,2-dihydroxy compounds were also detected on occasion. Some trihydroxy compounds were suggested. This is of interest because the trihydroxylated metabolites have been pointed out as precursors of ultimate carcinogen of MC recently. The high sensitivity of the lung to MC carcinogenesis was not interpreted only by specific distribution in tissue of metabolites of the hydrocarbon.

摘要

用乙醇或乙酸乙酯直接或在去除结合物后,提取大鼠和小鼠组织及排泄物中3-甲基胆蒽的代谢产物,通过葡聚糖凝胶LH-20柱色谱法进行纯化,并采用气相色谱-质谱分析进行检测。本实验数据表明,色谱纯化后的提取物被一些组织衍生的甾醇(如胆固醇)污染。作为与3-甲基胆蒽相关的化合物,在提取物中鉴定出一种脱氢化合物、1-和2-羟基化合物、11-苯酚以及另外两种苯酚。偶尔也检测到一些酮类和顺式-1,2-二羟基化合物。还推测出一些三羟基化合物。这一点很有意思,因为最近有人指出三羟基化代谢产物是MC最终致癌物的前体。肺部对MC致癌作用的高敏感性不能仅仅通过烃类代谢产物在组织中的特定分布来解释。

相似文献

1
Gas chromatography-mass spectrometric analysis of 3-methyl-cholanthrene metabolism in vivo.体内3-甲基胆蒽代谢的气相色谱-质谱分析。
Gan. 1980 Apr;71(2):181-9.
2
Chromatographic separation of autofluorescent and quenching substances from the hydrocarbon in tissue.从组织中的碳氢化合物中对自发荧光物质和猝灭物质进行色谱分离。
Gan. 1975 Feb;66(1):21-7.
3
Microsomal hydroxylation of 3-methylcholanthrene: analysis by computerized gas chromatography-mass spectrometry.3-甲基胆蒽的微粒体羟基化作用:通过计算机化气相色谱-质谱分析法进行分析
J Chromatogr. 1983 May 6;260(2):429-38. doi: 10.1016/0021-9673(83)80050-8.
4
Metabolism of the carcinogen 3-methylcholanthrene in human bone marrow preparations.致癌物3-甲基胆蒽在人骨髓制剂中的代谢
Drug Metab Dispos. 1990 Sep-Oct;18(5):664-9.
5
Persistent binding of 3-methylcholanthrene to mouse lung DNA and its correlation with susceptibility to pulmonary neoplasia.3-甲基胆蒽与小鼠肺DNA的持续结合及其与肺肿瘤易感性的相关性。
Cancer Res. 1979 Jul;39(7 Pt 1):2400-5.
6
Chromatographic analyses of 3-methylcholanthrene metabolism in adult and fetal mice and the occurrence of conjugating enzymes in the fetus.成年和胎儿小鼠中3-甲基胆蒽代谢的色谱分析以及胎儿中结合酶的出现情况。
Cancer Res. 1975 Mar;35(3):613-20.
7
Changes of sterol metabolism during 3-methylcholanthrene-induced mouse skin carcinogenesis.3-甲基胆蒽诱导小鼠皮肤致癌过程中甾醇代谢的变化。
Gan. 1981 Feb;72(1):38-44.
8
The metabolism of 3-methylcholanthrene and some related compounds by rat-liver homogenates.大鼠肝脏匀浆对3-甲基胆蒽及一些相关化合物的代谢作用
Biochem J. 1966 Jan;98(1):215-28. doi: 10.1042/bj0980215.
9
Metabolism of 3-methylcholanthrene in rat liver cytosol.3-甲基胆蒽在大鼠肝细胞溶质中的代谢
Chem Biol Interact. 1989;71(4):393-401. doi: 10.1016/0009-2797(89)90113-0.
10
Metabolism of [3H]-methylcholanthrene in the perfused rat liver.
Cancer Res. 1977 Feb;37(2):369-75.

引用本文的文献

1
Disruption of the gene for CYP1A2, which is expressed primarily in liver, leads to differential regulation of hepatic and pulmonary mouse CYP1A1 expression and augmented human CYP1A1 transcriptional activation in response to 3-methylcholanthrene in vivo.CYP1A2 基因的失活主要发生在肝脏,导致肝和肺组织中 CYP1A1 的表达受到不同程度的调控,并且在体内受到 3-甲基胆蒽的刺激后,人 CYP1A1 的转录激活增强。
J Pharmacol Exp Ther. 2010 Nov;335(2):369-79. doi: 10.1124/jpet.110.171173. Epub 2010 Aug 23.
2
Persistent induction of cytochrome P4501A1 in human hepatoma cells by 3-methylcholanthrene: evidence for sustained transcriptional activation of the CYP1A1 promoter.3-甲基胆蒽诱导人肝癌细胞细胞色素 P4501A1 的持续诱导:CYP1A1 启动子持续转录激活的证据。
J Pharmacol Exp Ther. 2010 Apr;333(1):99-109. doi: 10.1124/jpet.109.162222. Epub 2010 Jan 5.