Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
National Institute of Biology, Večna pot 111, Ljubljana, Slovenia.
Chemosphere. 2014 Nov;115:54-8. doi: 10.1016/j.chemosphere.2014.01.010. Epub 2014 Feb 18.
Imatinib mesylate (IM) is at present one of the most widely used cytostatic drugs in developed countries but information on its ecotoxicological activities is scarce. This article describes the results of the first investigation in which genotoxic and acute toxic properties of the drug were studied in higher plants. IM was tested in two widely used plant bioassays namely in micronucleus (MN) assays with meiotic tetrad cells of Tradescantia (clone #4430) and in mitotic root tip cells of Allium cepa. Additionally, acute toxic effects (inhibition of cell division and growth of roots) were monitored in the onions. Furthermore, we studied the impact of the drug on the fertility of higher plants in pollen abortion experiments with three wildlife species (Chelidonium majus, Tradescantia palludosa and Arabidopsis thaliana). In MN assays with Tradesacantia a significant effect was seen with doses ⩾10μM; the Allium MN assay was even more sensitive (LOEL⩾1.0μM). A significant decrease of the mitotic indices was detected at levels ⩾10μM in the onions and reduction of root growth with ⩾100μM. In the pollen fertility assays clear effects were observed at doses ⩾147.3mgkg(-1). Data concerning the annual use of the drug in European countries (France, Germany, Slovenia) enable the calculation of the predicted environmental concentration (PEC) values which are in the range between 3.3 and 5.0ngL(-1). Although comparisons with the genotoxic potencies of other commonly used cytostatic drugs and with highly active heavy metal compounds show that IM is an extremely potent genotoxin in higher plants, it is evident that the environmental concentrations are ⩾5 orders of magnitude lower as the levels which are required to cause adverse effects.
甲磺酸伊马替尼（IM）目前是发达国家应用最广泛的细胞抑制剂之一，但有关其生态毒理学活性的信息却很少。本文描述了首次研究该药物在高等植物中的遗传毒性和急性毒性的结果。该药物在两个广泛使用的植物生物测定法中进行了测试，即用于生殖细胞四分体的微核（MN）测定法（Tradescantia （克隆#4430））和用于洋葱根尖细胞的有丝分裂测定法。此外，还在洋葱中监测了药物对急性毒性的影响（抑制细胞分裂和根系生长）。此外，我们还研究了该药物对三种野生植物（Chelidonium majus、Tradescantia palludosa 和 Arabidopsis thaliana）花粉败育实验中高等植物繁殖力的影响。在 Tradesacantia 的 MN 测定中，剂量≥10μM 时观察到明显的作用；而 Allium MN 测定更为敏感（LOEL≥1.0μM）。在洋葱中，在≥10μM 的水平下检测到有丝分裂指数显著下降，在≥100μM 时检测到根生长减少。在花粉育性测定中，在剂量≥147.3mgkg(-1)时观察到明显的作用。关于欧洲国家（法国、德国、斯洛文尼亚）每年使用该药物的数据，可以计算出预测的环境浓度（PEC）值，范围在 3.3 到 5.0ngL(-1)之间。尽管与其他常用细胞抑制剂的遗传毒性潜力以及与高活性重金属化合物的比较表明，IM 是高等植物中一种非常有效的遗传毒物，但显然环境浓度至少低 5 个数量级，因为达到有害影响所需的水平要低得多。
