Chronic toxicity of hexabromocyclododecane(HBCD) induced by oxidative stress and cell apoptosis on nematode Caenorhabditis elegans.

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.