State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, School of Resources and Environmental Engineering, East China University of Science and Technology, Shanghai, 200237, PR China.
Research Institute of Wastes and Soil Remediation, Shanghai Academy of Environmental Sciences, Shanghai, 200233, PR China.
Chemosphere. 2018 Oct;208:31-39. doi: 10.1016/j.chemosphere.2018.05.147. Epub 2018 May 25.
In order to gain insights into the chronic effects and mechanisms of hexabromocyclododecane (HBCD), the animal model Caenorhabditis elegans (C. elegans) was chosen for toxicity study. Multiple endpoints, including the physiological (growth and locomotion behaviors), biochemical (reactive oxygen species (ROS) production, lipofuscin accumulation, and cell apoptosis), and molecular (stress-related gene expressions) levels, were tested by chronic exposure for 10 d to low concentrations of HBCD (0.2 nM-200 nM). The results revealed that chronic exposure to HBCD at concentrations more than 20 nM would significantly influence the growth, locomotion behaviors, ROS formation, lipofuscin accumulation, and cell apoptosis of nematodes. Treatment with antioxidants of ascorbate and N-acetyl-l-cysteine (NAC) suppressed the toxicity induced by HBCD. The integrated gene expression profiles showed that the chronic exposure to 200 nM of HBCD significantly increased the expression levels of stress-related genes (e.g., hsp-16.2, hsp-16.48, sod-1, sod-3, and cep-1 genes). Among these genes, the sod-1, sod-3, and cep-1 gene expressions were significantly correlated with HBCD-induced physiological effects by the Pearson correlation test. The mutations of sod-3 and cep-1 induced more severe toxicity compared to wild-type nematodes. Therefore, HBCD exposure induced oxidative stress by ROS accumulation and cell apoptosis, which resulted in HBCD-induced toxicity on nematodes, and sod-3 and cep-1 played important roles in protecting nematodes against HBCD-induced toxicity.
为了深入了解六溴环十二烷（HBCD）的慢性效应和作用机制，选择动物模型秀丽隐杆线虫（C. elegans）进行毒性研究。通过慢性暴露于低浓度 HBCD（0.2 nM-200 nM）10 d，测试了多个终点，包括生理（生长和运动行为）、生化（活性氧（ROS）产生、脂褐素积累和细胞凋亡）和分子（应激相关基因表达）水平。结果表明，慢性暴露于浓度超过 20 nM 的 HBCD 会显著影响线虫的生长、运动行为、ROS 形成、脂褐素积累和细胞凋亡。抗氧化剂抗坏血酸和 N-乙酰-L-半胱氨酸（NAC）的处理抑制了 HBCD 诱导的毒性。综合基因表达谱显示，慢性暴露于 200 nM 的 HBCD 显著增加了应激相关基因（如 hsp-16.2、hsp-16.48、sod-1、sod-3 和 cep-1 基因）的表达水平。在这些基因中，通过 Pearson 相关性检验，sod-1、sod-3 和 cep-1 基因的表达与 HBCD 诱导的生理效应显著相关。sod-3 和 cep-1 的突变与野生型线虫相比，引起更严重的毒性。因此，HBCD 暴露通过 ROS 积累和细胞凋亡引起氧化应激，导致 HBCD 对线虫产生毒性，sod-3 和 cep-1 在保护线虫免受 HBCD 诱导的毒性方面发挥重要作用。
