Key Laboratory of Environmental Medicine Engineering in Ministry of Education, Department of Biochemistry and Molecular Biology, Medical School of Southeast University, Nanjing, China.
PLoS One. 2012;7(8):e43729. doi: 10.1371/journal.pone.0043729. Epub 2012 Aug 17.
Dimercaptosuccinic acid (DMSA) coating improves the uptake efficiency presumably by engendering the Fe(2)O(3)-NPs. In the present study, we investigated the possible environmental safety concentrations of Fe(2)O(3)-NPs using different assay systems in nematode Caenorhabditis elegans with lethality, development, reproduction, locomotion behavior, pharyngeal pumping, defecation, intestinal autofluorescence and reactive oxygen species (ROS) production as the endpoints. After exposure from L4-larvae for 24-hr, DMSA coated Fe(2)O(3)-NPs at concentrations more than 50 mg/L exhibited adverse effects on nematodes. After exposure from L1-larvae to adult, DMSA coated Fe(2)O(3)-NPs at concentrations more than 500 μg/L had adverse effects on nematodes. After exposure from L1-larvae to day-8 adult, DMSA coated Fe(2)O(3)-NPs at concentrations more than 100 μg/L resulted in the adverse effects on nematodes. Accompanied with the alterations of locomotion behaviors, ROS production was pronouncedly induced by exposure to DMSA coated Fe(2)O(3)-NPs in the examined three assay systems, and the close associations of ROS production with lethality, growth, reproduction, locomotion behavior, pharyngeal pumping, defecation, or intestinal autofluorescence in nematodes exposed to DMSA coated Fe(2)O(3)-NPs were confirmed by the linear regression analysis. Moreover, mutations of sod-2 and sod-3 genes, encoding Mn-SODs, showed more susceptible properties than wild-type when they were used for assessing the DMSA coated Fe(2)O(3)-NPs-induced toxicity, and the safety concentrations for DMSA coated Fe(2)O(3)-NPs should be defined as concentrations lower than 10 μg/L in sod-2 and sod-3 mutant nematodes.
二巯丁二酸(DMSA)涂层通过生成 Fe(2)O(3)-NPs 提高了摄取效率。在本研究中,我们使用线虫秀丽隐杆线虫的不同测定系统,以致死率、发育、繁殖、运动行为、咽泵吸、排粪、肠道自发荧光和活性氧(ROS)产生为终点,研究了 Fe(2)O(3)-NPs 的可能环境安全浓度。暴露于 L4 幼虫 24 小时后,浓度高于 50mg/L 的 DMSA 涂层 Fe(2)O(3)-NPs 对线虫表现出不良影响。从 L1 幼虫暴露到成虫后,浓度高于 500μg/L 的 DMSA 涂层 Fe(2)O(3)-NPs 对线虫有不良影响。从 L1 幼虫暴露到第 8 天成虫后,浓度高于 100μg/L 的 DMSA 涂层 Fe(2)O(3)-NPs 导致线虫出现不良影响。伴随着运动行为的改变,在三个检测系统中,暴露于 DMSA 涂层 Fe(2)O(3)-NPs 显著诱导了 ROS 的产生,并且通过线性回归分析证实了 ROS 产生与线虫暴露于 DMSA 涂层 Fe(2)O(3)-NPs 时的致死率、生长、繁殖、运动行为、咽泵吸、排粪或肠道自发荧光之间的密切关联。此外,编码 Mn-SOD 的 sod-2 和 sod-3 基因突变体比野生型对线粒体 DMSA 涂层 Fe(2)O(3)-NPs 诱导的毒性更为敏感,DMSA 涂层 Fe(2)O(3)-NPs 的安全浓度应定义为 sod-2 和 sod-3 突变体线虫中浓度低于 10μg/L 的浓度。