Chronic nanoparticulate silver exposure results in tissue accumulation and transcriptomic changes in zebrafish

Increasing utilization of metallic nanomaterials in recent years implies an increasing rate of release to the environment, with potentially serious adverse effects on environmentally important species. Previously, we demonstrated that exposure to nanoparticulate silver for 24-48 h results in dramatic alterations in global gene expression patterns and increased tissue burdens in zebrafish gills. The present study reports outcomes associated with chronic exposure to nanoparticulate silver in zebrafish. Adult female Danio rerio were exposed to 5, 15, 25, or 50 μg/L nanoparticulate silver in a time course up to 28 days. A soluble silver treatment (5 μg/L) was also included. Results indicate that use of flow-through systems for chronic nanometal studies is a viable concept; measured concentrations of approximately 60% of nominal values over the course of the 28-day exposure were observed. Dissolution of nanoparticulate silver was measured twice weekly throughout the exposure ranging between 0.5 and 1.0 μg/L, and was relatively consistent between nanoparticulate silver tanks, with no differences between treatments. Gill samples from the 28-day time point were analyzed for global gene expression patterns and histopathology. Tissue accumulation in both gill and eviscerated carcass was dose-dependent, and remained elevated 4 days after the silver was removed. Microarray analysis also revealed a dose-dependent response pattern, with the largest number of genes affected in the 50 μg/L AgNP exposure. Pathway analysis of affected genes identified a number of GO terms that were significantly over-represented in the high AgNP dataset. These terms are associated with DNA damage repair, cellular restructuring, and developmental processes.