An integrated functional genomic study of acute phenobarbital exposure in the rat

摘要: Non-genotoxic carcinogens are notoriously difficult to identify as they do not damage DNA directly and have diverse modes of action, necessitating long term in vivo studies. The early effects the classic rodent non-genotoxic hepatocarcinogen phenobarbital been investigated Fisher rat using a combination metabolomics transcriptomics, investige stage mechanistic changes that predictive longer pathology. Liver blood plasma were profiled across 14 days, multivariate statistics used perturbed pathways. Both transcriptomics detected liver which dose dependent, even after one day exposure. Integration two datasets associated perturbations with specific Hepatic glycogen was decreased due decrease synthesis, triglycerides an increase fatty acid uptake by liver. succinate increased this heme biosynthesis. Glutathione synthesis also increased, presumably response oxidative stress. Liquid Chromatography Mass Spectrometry demonstrated remodeling lipid species, possibly resulting from proliferation smooth endoplasmic reticulum. data fusion metabolomic transcriptomic proved be highly sensitive approach for monitoring altered hepatic metabolism, stress cytochrome P450 induction simultaneously. This is particularly useful interpreting metabolites such hubs metabolism.