Abstract
In this study, we investigated global gene expression in rats treated with four hepatocarcinogens. Twenty-five rats were divided randomly into five groups (n=5 per group), and animals of each group were orally intubated with prednisolone, dehydroepiandrosterone, hydrocortisone, lithocholic acid or vehicle (DMSO), respectively. All animals were sacrificed at 48 h after chemical treatment. At necropsy, half of livers were fixed in 10% phosphate-buffered formalin, and routinely processed for embedding in paraffin, and staining of 4 mm sections with hematoxylin and eosin for histopathological examination. And the remaining samples from all the animals were snap-frozen in liquid nitrogen for RNA extraction and subsequent analysis. Gene set enrichment analysis (GSEA) analysis represented that Gene Set associated with hepatocarcinogenesis were discovered as showing up-regulated genes from 1<SUP>st</SUP> to 50<SUP>th </SUP>including xenobiotic genes such as ‘chemokine(C-Cmotif) receptor 3’ and down-regulated genes from 1<SUP>st</SUP> to 50<SUP>th</SUP> including xenobiotic genes such as ‘proteosome’. KEGG pathway analysis showed that fifteen pathways such as ‘MAPK signaling pathway’ were related to up-regulated genes and fifteen pathways such as ‘biosynthesis of steroid’ and regulation of actin cytoskeleton’ were associated with down-regulated genes. Our results suggest that it may be feasible to differentiate active and inactive hepatocarcinogens by GSEA and KEGG pathway analysis.
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