Can Transcriptomic Profiles from Cancer Cell Lines be Used for Toxicity Assessment

In vitro toxicogenomics (TGx) has the potential to replace or supplement animal studies. However, TGx studies often suffer from limited sample size and cell types. Meanwhile, transcriptomic data have been generated for tens of thousands of compounds using cancer cell lines mainly for drug efficacy screening. Here, we asked the question of whether these types of transcriptomic data can be used to support toxicity assessment. We compared transcriptomic profiles from three cancer lines (HL60, MCF7, and PC3) from the CMap dataset with those using primary hepatocytes or in vivo repeated dose studies from the Open TG-GATEs database by using our previously reported Pair Ranking (PRank) method. We observed an encouraging similarity between HL60 and human primary hepatocytes (PRank score = 0.70), suggesting the two cellular assays could be potentially interchangeable. By the analysis was limited to DILI-related compounds or genes, the cancer cell lines exhibited promise in DILI assessment in comparison with conven...