| Popis: |
To further investigate the effects of tunicamycins (TMs) at the molecular level, a toxicogenomic approach was developed to examine the differential gene expression between cultured rat hepatocytes exposed to TMs at low levels and untreated cultured hepatocytes. It was found that exposure of in vitro cultured rat hepatocytes to 0.05 and 50 µM TMs resulted in 38 and 34 genes expressed at significantly different levels, respectively, compared to untreated hepatocyte controls. Statistical analysis of the 51 genes (including housekeeping genes) presented on the DualChip® rat hepato revealed that 24 genes (47%) were upregulated, 14 genes (27%) were downregulated and 13 genes (39%) remained stable following treatment with TMs at 0.05 µM. Dosed at a TMs concentration of 50 µM, 26 genes (50%) were upregulated, eight genes (16%) were downregulated and 17 genes (34%) remained stable. The most highly induced genes consistent within both treatments were: FN, ecoa, MnSOD, mt_Co1 and Osteon, Their functions, including oxidative metabolism and detoxification of radicals which are toxic to biological systems, drug metabolism, lyase activity/β-oxidation and maintaining the integrity of the extracellular matrix, are consistent with expected upregulation following a toxic insult. This toxicogenomic approach to defining the effect of exposure of in vitro cultured rat hepatocytes to tunicamycins will complement previous works that have focused primarily on toxicology, pathology and pathogenesis associated with acute exposure to TMs. |
