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由小鼠微核频率和血红蛋白加合物水平确定的缩水甘油的遗传毒性强度。

The genotoxic potency of glycidol established from micronucleus frequency and hemoglobin adduct levels in mice.

作者信息

Aasa Jenny, Abramsson-Zetterberg Lilianne, Carlsson Henrik, Törnqvist Margareta

机构信息

Department of Environmental Science and Analytical Chemistry, Stockholm University, Sweden.

National Food Agency, Uppsala, Sweden.

出版信息

Food Chem Toxicol. 2017 Feb;100:168-174. doi: 10.1016/j.fct.2016.12.022. Epub 2016 Dec 22.

DOI:10.1016/j.fct.2016.12.022
PMID:28012894
Abstract

Glycidol is a genotoxic animal carcinogen that has raised concern due to its presence in food, as glycidyl fatty acid esters. Here we investigated the genotoxicity of glycidol in BalbC mice (0-120 mg/kg) by monitoring the induction of micronuclei in peripheral blood as a marker of chromosomal damage. The scoring of the micronuclei was assessed by flow cytometry. In the treated mice, the internal dose of glycidol, expressed as area under the concentration-time curve, AUC (mol × L × h; Mh), was measured by dihydroxypropyl adducts to hemoglobin (Hb). The study showed that glycidol induced linear dose-dependent increases of Hb adducts (20 pmol/g Hb per mg/kg) and of micronuclei frequencies (12‰ per mMh). Compared to calculations based on administered dose, an improved dose-response relationship was observed when considering internal dose, achieved through the applied combination of sensitive techniques used for the scoring of micronuclei and AUC estimation of glycidol in the same mice. By comparing with earlier studies on micronuclei induction in mice exposed to ionizing radiation we estimated the radiation dose equivalent (rad-eq.) of glycidol to be ca 15 rad-eq./mMh.

摘要

缩水甘油是一种具有基因毒性的动物致癌物,由于其以缩水甘油脂肪酸酯的形式存在于食品中而引发了关注。在此,我们通过监测外周血中微核的诱导情况(作为染色体损伤的标志物),研究了缩水甘油在BalbC小鼠体内(0 - 120毫克/千克)的基因毒性。微核的计分通过流式细胞术进行评估。在接受处理的小鼠中,缩水甘油的体内剂量以浓度 - 时间曲线下面积(AUC,摩尔×升×小时;Mh)表示,通过血红蛋白(Hb)的二羟丙基加合物来测量。研究表明,缩水甘油诱导Hb加合物呈线性剂量依赖性增加(每毫克/千克为20皮摩尔/克Hb)以及微核频率增加(每毫摩尔×小时为12‰)。与基于给药剂量的计算相比,当考虑体内剂量时观察到了更好的剂量 - 反应关系,这是通过对同一小鼠中用于微核计分和缩水甘油AUC估计的敏感技术的联合应用实现的。通过与早期关于暴露于电离辐射的小鼠中微核诱导的研究进行比较,我们估计缩水甘油的辐射剂量当量(rad - eq.)约为15 rad - eq./毫摩尔×小时。

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