Rat life cycle liver gene expression

ABSTRACT: Age- and sex-related susceptibility to adverse drug reactions is a key concern in understanding drug safety and disease progression. We hypothesize that the underlying suite of hepatic genes expressed at various developmental and life-cycle stages will impact susceptibility to adverse drug reactions. Thus, understanding the basal expression patterns of genes throughout the life span of the rat model species in both sexes will inform our assessments of adverse drug reactions. The liver plays a central role in the metabolism and biotransformation of drugs via key cellular pathways. Untreated, male and female F344 rats were sacrificed at 2, 5, 6, 8, 15, 21, 52, 78, and 104 weeks of age. Liver tissues were collected for histology and gene expression analysis. Whole-genome rat microarrays (44,000 features) were used to query global expression profiles. An initial list of active genes was selected using a 2-way ANOVA with a p-value cutoff of 0.05 and 1.5 fold-change difference from mean expression. Three dimensional principal component analyses revealed notable expression profile divergence between males and females after 5 weeks with greatest differences observed at 21 and 52 weeks before converging again at 104 weeks. Furthermore, k-means clustering identified groups of genes that displayed specific developmental and age-related patterns of expression. Various adult aging-related clusters included genes involved in pathways related to susceptibility to adverse drug effects such as xenobiotic metabolism, DNA damage repair, and oxidative stress. These results suggest an underlying role for genes in these specific clusters in potentiating age- and sex-related susceptibilities to adverse health effects.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE21335 | GEO | 2010/06/24

SECONDARY ACCESSION(S): PRJNA126147

REPOSITORIES: GEO