In vitro murine embryonic microRNA expression signatures predicting the non-genotoxic carcinogenic potential of chemicals

The human body is continuously exposed to various compounds that could initiate or accelerate cancer development. Such carcinogenic compounds can be classified into a genotoxic and non-genotoxic group. Especially carcinogenicity of non-genotoxic compounds is difficult to determine with current in vitro assessments and therefore has to be improved urgently. Here, we used a toxicogenomics-based approach by genome-wide microRNA expression profiling of mouse embryonic stem (mES) cells to identify microRNA classifiers for genotoxic carcinogens (GTXC), non-genotoxic carcinogens (NGTXC) and oxidative (Ox) compounds. We exposed mES cells to four different NGTXC, four GTXC and four Ox compounds. Differential microRNA expression was determined 4, 8 and 12 hours after exposure and was used to assess its discriminative power for NGTXC and GTXC. We generated an accurate classifier set, which was discriminative for NGTXC using a tiered approach. In conclusion, our study indicates that microRNA expression profiles can discriminate between NGTXC, GTXC and Ox compounds with high accuracy. 146 mES samples in total, 2 control mock treatments, replicates per treated group n=3-4