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大鼠肝脏中体内形成的主要黄曲霉毒素B1-DNA加合物的鉴定。

Identification of the principal aflatoxin B1-DNA adduct formed in vivo in rat liver.

作者信息

Croy R G, Essigmann J M, Reinhold V N, Wogan G N

出版信息

Proc Natl Acad Sci U S A. 1978 Apr;75(4):1745-9. doi: 10.1073/pnas.75.4.1745.

Abstract

The products of in vivo covalent binding of activated aflatoxin B1 (AFB1) to DNA have been investigated in rats. The principal covalent product formed in liver DNA of rats treated with AFB1 has been identified as 2,3-dihydro-2-(N7-guanyl)-3-hydroxy-aflatoxin B1. This compound was isolated from the liver DNA of rats dosed with AFB1 (2.0 mg/kg) in sufficient quantity for characterization by physicochemical techniques, including field-desorption mass spectrometry. This information together with results of chemical methylation of the compound proved that the major adduct formed between DNA and AFB1 in vivo is identical to that produced in vitro when AFB1 is incubated with DNA in the presence of a rat liver microsomal activating system. Quantitative studies of formation of this compound revealed a dose-dependent relationship between the level of its occurence in liver DNA and AFB1 doses over the range 0.125-1.0 mg/kg.

摘要

已在大鼠中研究了活化黄曲霉毒素B1(AFB1)与DNA的体内共价结合产物。在用AFB1处理的大鼠肝脏DNA中形成的主要共价产物已被鉴定为2,3-二氢-2-(N7-鸟嘌呤基)-3-羟基黄曲霉毒素B1。该化合物从用AFB1(2.0mg/kg)给药的大鼠肝脏DNA中分离出来,其数量足以通过包括场解吸质谱法在内的物理化学技术进行表征。该信息与该化合物的化学甲基化结果一起证明,DNA与AFB1在体内形成的主要加合物与在大鼠肝脏微粒体活化系统存在下将AFB1与DNA一起孵育时在体外产生的加合物相同。对该化合物形成的定量研究表明,在0.125-1.0mg/kg范围内,其在肝脏DNA中的出现水平与AFB1剂量之间存在剂量依赖关系。

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本文引用的文献

2
THE STRUCTURES OF AFLATOXINS B AND G.黄曲霉毒素B和G的结构
J Am Chem Soc. 1965 Feb 20;87:882-6. doi: 10.1021/ja01082a031.
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ACUTE TOXICITY OF AFLATOXIN B-1 IN RATS.黄曲霉毒素B-1对大鼠的急性毒性
Br J Cancer. 1964 Dec;18(4):756-62. doi: 10.1038/bjc.1964.87.
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The total synthesis of racemic aflatoxin B1.外消旋黄曲霉毒素B1的全合成。
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