Analysis of mixture toxicity for dual combinations of heavy metals and herbicides using toxicogenomic approach

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The single chemical cytotoxicity showed that heavy metals and silver nanoparticles had high toxicity, respectively, but herbicides had relatively low toxicity. In contrast, the dual combinations cytotoxicity showed that the combination of silver nanoparticles and heavy metals tended to be much more toxic than silver nanoparticles or heavy metals alone, excluding the combination of silver nanoparticles and chromium (AgNPs-Cr). However, the toxicity of the combination of herbicides and heavy metals was similar to that of herbicides exposure alone. From cytotoxicity results, 5 μM of silver nanoparticles, 2.6 μM of cadmium, 7μM of arsenic and 1.1 μM of chromium were used for the DNA microarray analyses to further elucidate the mechanisms of mixture toxicity. The treatments with AgNPs-Cd (70% cytoviability), AgNPs-As (100% cytoviability) and AgNPs-Cr (140% cytoviability) altered the expression levels of 107 genes, 500 genes and 196 genes, respectively. There was a significant difference between 2 combinations (AgNPs-Cr and AgNPs-Cd) and silver nanoparticles alone on DNA replication genes such as MCM2, MCM5, MCM6, and GINS2 that are important for DNA replication fork. Furthermore, FABP1 gene was down regulated 41-fold by AgNPs-As combination. FABPs play an important role in the transport of lipids to specific compartments in the cell. In conclusion, toxicogenomic approach could elucidate synergistic toxicity by AgNPs and heavy metals, which clearly demonstrate the possible use of DNA microarray analysis for evaluation of mixture toxicity.