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首页> 外文期刊>The Journal of toxicological sciences >Tissue distributions of 4-(hydroxymethylnitrosamino)-1-(3-pyridyl)-1-butanone glucuronide, a stable form of reactive intermediate produced from 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, in the rat
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Tissue distributions of 4-(hydroxymethylnitrosamino)-1-(3-pyridyl)-1-butanone glucuronide, a stable form of reactive intermediate produced from 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, in the rat

机译：4-（羟甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮葡糖醛酸的组织分布，它是由4-（甲基亚硝基氨基）-1-（3-吡啶基）-1-丁酮产生的反应性中间体的稳定形式。鼠

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摘要

The tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), induces lung tumors in rodents and has been suggested as a causative factor in human lung cancer. NNK is activated by α-hydroxylation at either the methyl or methylene carbon adjacent to the N-nitroso group to yield unstable intermediates that spontaneously decompose to produce alkylating agents. 4-(Hydroxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (HO-methyl NNK) glucuronide, a glucuronide of the reactive intermediate of NNK has been identified. However, there are no available data concerning HO-methyl NNK glucuronide. In the present study, we investigated the tissue distribution of HO-methyl NNK glucuronide in control and phenobarbital (PB)-treated rats after intraperitoneal administration of NNK. In PB-treated rats, HO-methyl NNK glucuronide was detected in plasma, kidney, liver, lung, and pancreas. On the contrary, in the control rats, HO-methyl NNK glucuronide was detected only in plasma, kidney and liver at low concentrations compared with PB-treated rats. The results of cumulative urinary excretion of HO-methyl NNK glucuronide in Wistar and Gunn rats suggested that PB-inducible UDP-glucuronosyltransferase 2B isoforms mainly contribute to the formation of HO-methyl NNK glucuronide.
机译：烟草特有的亚硝胺4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）在啮齿动物中诱发肺部肿瘤，并已被认为是人类肺癌的病因。 NNK通过与N-亚硝基相邻的甲基或亚甲基上的α-羟基化而活化，从而生成不稳定的中间体，该中间体会自发分解以生成烷基化剂。已经鉴定出4-（羟基甲基亚硝氨基）-1-（3-吡啶基）-1-丁酮（HO-甲基NNK）葡糖醛酸，其为NNK的反应性中间体的葡糖醛酸。然而，没有关于HO-甲基NNK葡糖醛酸苷的可用数据。在本研究中，我们研究了腹膜内给予NNK后，对照组和苯巴比妥（PB）处理的大鼠中HO-甲基NNK葡糖醛酸的组织分布。在PB治疗的大鼠中，在血浆，肾脏，肝脏，肺和胰腺中检测到HO-甲基NNK葡糖醛酸。相反，在对照大鼠中，与PB处理的大鼠相比，仅在血浆，肾脏和肝脏中检测到低浓度的HO-甲基NNK葡糖醛酸。 Wistar和Gunn大鼠的HO-甲基NNK葡萄糖醛酸化物累积尿排泄的结果表明，PB诱导的UDP-葡萄糖醛酸糖基转移酶2B亚型主要促进HO-甲基NNK葡萄糖醛酸化物的形成。

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