Transcriptomic analyses of the liver in female mice exposed to 1,4-dioxane in drinking water

We evaluated liver tissues of B6D2F1/Crl mice exposed to 0, 40, 200, 600, 2000, or 6000 ppm 1,4-dioxane in drinking water for 7, 28, or 90 days in support of an investigation of the mode of action for 1,4-dioxane-induced murine liver tumors. TempO-Seq technology was used to measure global hepatic gene expression. Exposure-induced transcriptional responses increased by dose and exposure duration, with few differentially expressed genes at 40 and 200 ppm regardless of exposure duration. Pathway enrichment analysis identified significant perturbations in pathways associated with xenobiotic metabolism, complement and coagulation cascades and fatty acid metabolism in 600, 2000, and 6000 ppm groups at all timepoints compared to time-matched control groups. A significant transcriptomic proliferative response was only observed in 6000 ppm exposed mice at 90 days. Differential gene expression and pathway enrichment analysis results suggest 600 ppm as a potential threshold concentration for hepatic transcriptomic response to 1,4-dioxane in female mice. RNA sequencing data were used to examine the transcriptomic response in the livers of female mice exposed to 1,4-dioxane in the drinking water by comparing liver tissue from 6 treatment groups at 3 different timepoints.