p53 Contributes to Differentiating Gene Expression following Exposure to Acetaminophen and Its Less Hepatotoxic Regioisomer Both In Vitro and In Vivo

摘要: The goal of the present study was to compare hepatic toxicogenomic signatures across in vitro and vivo mouse models following exposure acetaminophen (APAP) or its relatively nontoxic regioisomer 3′-hydroxyacetanilide (AMAP). Two different Affymetrix microarray platforms one Agilent Oligonucleotide were utilized. APAP AMAP treatments resulted significant large changes gene expression that quite disparate, likely related their toxicologic profiles. Ten transcripts, all which have been implicated p53 signaling, identified as differentially regulated at time-points multiple platforms. Protein-level quantification activity aligned with results from transcriptomic analysis, thus supporting mechanism APAP-induced toxicity. Therefore, this provide good evidence phosphorylation an altered p53-driven transcriptional response are fundamental steps