Expression Profiling of Drug Metabolizing Enzymes in Rat Syncytiotrophoblast Cell Lines

Abstract

TR-TBT-18d-1 and -18d-2 are syncytiotrophoblast cell lines established from the placenta of a transgenic rat harboring a temperature-sensitive simian virus 40 large T-antigen (Tg-rat). To explore the functional roles of drug metabolizing enzymes in the syncytiotrophoblasts of the placenta, we analyzed the gene expression of both cytochrome P450 (CYP) and phase II conjugation enzymes in these TR-TBT cell lines. A relatively high level of expression of CYP1A1 and CYP2C11 was detectable in the 18d-1 cells whereas CYP2E1 was more strongly expressed in the 18d-2 cells. A moderate degree of expression of CYP2B2 and CYP3A, and low expression of CYP1A2, was observed in both cell lines, but no CYP3A2 was detectable in either. Relatively high levels of SULT2 family gene expression were also evident in these TR-TBT cells, although the SULT1 family genes were found to be either absent or present at only moderate levels. Strong expression of both the UGT1 and UGT2 subfamily, and also the glutathione S-transferase (GST) subfamily, was also observed in both cell lines. These results suggest that TR-TBT cells are a useful model system for the study of syncytiotrophoblasts, which act as a protective fetal barrier against harmful xenobiotics.