Hera strives to provide its clients with superior preclinical toxicology and efficacy research from model creation to data delivery. Below are the summaries of our presentations from the Society of Toxicology – Annual Meeting 2017 and the American Association for Cancer Research – Annual Meeting 2017.
Effect of Transfecting HepG2 with Human CYP Enzymes on Chemical Toxicity
HepG2, a human liver cancer-derived cell line, is one of the most commonly used cell systems in toxicity screening with the advantages of unlimited life-span and supply, and stable phenotype. To provide an in vitro cell system to identify specific CYP-mediated cytotoxicity, we evaluated the cytotoxicity of selected chemicals in HepG2 cells stably transfected with individual human CYP enzymes and NADPH-cytochrome P450 oxidoreductase (CYP reductase/HPOR) knockout (KO) HepG2 cells.
This study illustrates that the utility of human CYP-expressing HepG2 cell lines to study the role of specific human CYP enzymes in chemical-induced cytotoxicity, and allowed us to conclude:
- A cell line overexpressing Cyp3A4 is more sensitive to Aflatoxin B1cytotoxicity than the corresponding WT cell line.
- Together these cell lines can be used for reaction phenotyping (determining which CYP is primarily responsible for the metabolism of a new drug).
- By incubating specific cell lines with a well characterized model substrate of that specific CYP and then monitoring subsequent metabolism, these cells can be used to detect if any CYPs are inhibited by the new compound.
A Novel Immunodeficient Rat for Modeling Human Cancer
At Hera, we have created an immunodeficient rat model with a functional deletion of the Rag2 gene. This knockout lacks mature B and T cells and also has a much lower proportion of NK cells compared to the SDR rat due to the knockout of the Il2rg. Furthermore, this rat model allowed for several commercially available human cancer cell lines, including human glioblastoma cell line U8yMG and the non-small cell lung cancer KRAS mutant cell line H358, to grow well. And studies are currently underway to characterize human cancer xenografts in the SRG rat and human patient-derived xenografts (PDX) in this model.