GSE248251 Comparison of transcriptomic profiles between HFPO-DA and positive controls for PPARa, PPARg or cytotoxicity in mouse, rat, and pooled human hepatocytes

Contributors : Melissa M Heintz ; William D Klaren ; Alexander W East ; Chad M Thompson ; Laurie C HawsSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiens ; Mus musculus ; Rattus norvegicusLike many per- or polyfluorinated alkyl substances (PFAS), toxicity studies with HFPO-DA (ammonium, 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate; CASRN 62037-80-3), a short-chain PFAS used in the manufacture of some types of fluorinated polymers, indicate that the liver is the primary target of toxicity in rodents following oral exposure. Although the current weight of evidence supports the PPARa mode of action (MOA) for liver effects in HFPO-DA-exposed mice, alternate MOAs have also been hypothesized including PPARg or cytotoxicity. To further evaluate the MOA for HFPO-DA in rodent liver, transcriptomic analyses were conducted on samples from primary mouse, rat and pooled human hepatocytes treated for 12, 24 or 72 hours with various concentrations of HFPO-DA, or established agonists of PPARa (GW7647), PPARg (rosiglitazone), or cytotoxic agents (i.e., acetaminophen or d-galactosamine). Concordance analyses of enriched pathways across chemicals within each species demonstrated greatest concordance between HFPO-DA and PPARa agonist GW7647-treated hepatocytes compared to the other chemicals evaluated. These findings were supported by benchmark concentration modeling and predicted upstream regulator results. In addition, transcriptomic analyses acros...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Mus musculus Rattus norvegicus Source Type: research