Literature-based network analysis of in vivo microarray data, which yields biologically relevant molecular networks from the dataset, is becoming an increasingly useful tool to identify nanoparticle-induced signaling. This approach can be used to discover molecules that contribute to endpoint health effects and otherwise unknown mechanisms of action. While animal inhalation exposures may be the most relevant for predicting human health effects of nanomaterials, it is not always feasible because of the vast number of particles being manufactured. Therefore, in vitro high-throughput screening (HTS) is being used to predict their potential toxicity. While HTS may be necessary, in vivo genomic studies still provide useful information for screening broad classes of nanomaterials. Similar to physiological experiments in which three results are expected-increase, decrease, and no change-the question of whether network-based genomics from in vivo studies is useful for in vitro screening can be answered yes, no, and maybe. The output from these studies provides significant molecular detail of an exposure. Advanced analysis can indicate specific transcription factors involved in the response, upstream, and downstream signaling, and also which cell type may be the most affected by a particular nanomaterial. However, there are challenges to converting genomic data from in vivo exposures to in vitro screening. These include responsiveness of the cell type in vitro vs observed in vivo changes, distinguishing temporal effects, and an isolated single cell response in vitro that lacks regulatory effects occurring in vivo. The in vivo genomic findings also have limitations including whether altered molecular networks from studies in rodents are applicable to the human, and therefore applicable to studies utilizing human cell lines. In addition, experimental design (e.g., dosing relevant to human exposure levels) should be evaluated when interpreting genomic analysis from in vivo studies. In summary, genomic analysis from in vivo studies, although not without limitations, can offer insight for HTS.
The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, March 10-14, 2013, San Antonio, Texas