Immortalized Human Liver Epithelial Cells (THLE-2)

The THLE-2 (Transformed Human Liver Epithelial-2) cell line is an immortalized human liver epithelial cell line derived from normal adult liver tissue obtained from the left lobe of a 64-year-old male donor with no clinical evidence of cancer. The cells were immortalized by introducing the simian virus 40 (SV40) large T antigen gene via retroviral transduction, a method that markedly extends the replicative lifespan of primary hepatocytes.

One of the most distinctive and critical advantages of THLE-2 cells is their non-tumorigenic phenotype when injected into athymic nude mice, their near-diploid karyotype, and the absence of alpha-fetoprotein (AFP) expression-key features that distinguish them from classical hepatoma cell lines like HepG2. Consequently, they represent a physiologically relevant, non-malignant human in vitro model that fills a crucial gap between primary human hepatocytes and transformed liver cancer cell lines.

The THLE-2 line retains functional cytochrome P450 (CYP) pathways, as confirmed by its ability to metabolize the procarcinogens benzo[a]pyrene, N‑nitrosodimethylamine, and aflatoxin B1 to their ultimate DNA-adducting metabolites. In addition, the cells maintain several Phase II enzymes and antioxidant systems, including glutathione S‑transferases, epoxide hydrolase, superoxide dismutase and catalase, enabling investigations into both xenobiotic metabolism and cellular defense mechanisms. The characteristically low background expression of P450 genes in untransfected THLE-2 cells additionally serves as an ideal platform for stable or transient transfection of individual CYP isoforms, facilitating targeted investigations of metabolite‑mediated hepatotoxicity with minimal interference from endogenous enzyme activity.