Toxicogenomic responses of the model ecoreceptor Caenorhabditis elegans to gold and silver nanoparticles


We used Au nanoparticles (Au-NPs) as a model for studying particle specific effects of manufactured nanomaterials (MNMs) by examining the toxicogenomic responses in a model soil organism, free living nematode Caenorhabditis elegans. Global genome expression for nematodes exposed to 4-nm citrate coated Au-NPs at the LC10 (5.9 mg L-1) revealed significant differential expression of 797 genes. The levels of expression for five genes (apl-1, dyn-1, act-5, abu-11, and hsp-4) were confirmed independently with qRT-PCR. Seven common biological pathways and one noncanonical Unfolded Protein Response (UPR) pathway associated with activation of 26 pqn/abu genes were identified. Inhibition with RNAi of one of the noncanonical UPR gene (abu-11) showed increased mortality in Au-NP exposed nematodes, suggesting possible involvement of abu-11 in a protective mechanism against Au-NPs. The results from experiments with Ag-NPs having two different coatings were presented in the previous report. More extensive analysis of microarray data this past year reveals that 7 of the up-regulated genes in response to citrate Ag-NP exposure were associated with different detoxification enzymes. Among these are glutathione-s-transferases, which are linked to activation of the glutathione metabolism pathway, nuclear localized metal responsive protein 2 kinases, and 7 C-type lectins. Important down-regulated genes on citrate Ag-NP exposed worms, were protein networks containing a major sperm-specific family, cysteine protease and lipase related proteins. Genes activated in response to PVP Ag-NPs were predominantly related to collagen and cuticle proteins. Independent qRT-PCR confirm significant differences in responses between Citrate- and PVP capped Ag-NP for 3 genes tested and also between Citrate-and PVP-NPs with Ag ions.