NTP screens chemicals for liver injury potential
When applied to human cell culture models, a high-throughput transcriptomics platform called TempO-Seq captures biological responses to chemicals that induce liver injury, according to a study by researchers at the National Toxicology Program (NTP) and NIEHS-funded colleagues. The novel approach may better predict the potentially harmful effects of a wide variety of environmental chemicals or pharmaceutical drugs in humans.
Predicting the responses of the human liver to chemical exposures is a major challenge in both pharmaceutical and toxicological research. To address this challenge, the researchers used TempO-Seq to generate high-throughput data for approximately 2,700 human transcripts with highly differentiated in vitro liver models that were exposed to wide-ranging concentrations of 24 reference compounds. This approach readily distinguished liver-injury compounds, such as the chemotherapy drug tamoxifen and pharmaceuticals that were withdrawn from the market (e.g., drug analogues), from compounds rarely associated with liver injury, such as caffeine and sucrose.
Moreover, the authors noted effective modeling of metabolically activated hepatic responses and leverage of the resolving power of concentration-response modeling to identify anticipated biological-response pathways that included hallmarks of liver function. The findings demonstrated that high-throughput transcriptomics, combined with differentiated in vitro liver models, might be an effective tool to model, explore, and interpret toxicological and pharmacological interactions. (JW)
Citation: Ramaiahgari SC, Auerbach SS, Saddler TO, Rice JR, Dunlap PE, Sipes NS, DeVito MJ, Shah RR, Bushel PR, Merrick BA, Paules RS, Ferguson SS. 2019. The power of resolution: contextualized understanding of biological responses to liver injury chemicals using high-throughput transcriptomics and benchmark concentration modeling. Toxicol Sci; doi: 10.1093/toxsci/kfz065 [Online 8 March 2019]. (Story)