The RPTEC/TERT1 cell line models key renal cell responses to the environmental toxicants, benzoapyrene and cadmium

We have characterized initial canonical responses to two environmental toxicants, cadmium (Cd) and benzoapyrene (BaP), in a novel in vitro model derived from renal proximal tubule epithelial cells (RPTEC) of a healthy human donor. The RPTEC/TERT1 cell line has been immortalized using the human telomerase reverse transcriptase (hTERT) subunit only and does not exhibit chromosomal abnormalities. RPTEC/TERT1 cells were exposed to single-compound and binary mixtures of Cd and BaP, known or suspected renal toxicants respectively. Cells exhibited cytotoxicity to concentrations of BaP and Cd as low as 1 nm and 3 μM, respectively. RPTEC/TERT1 cells exhibited compound-specific gene expression responses when exposed to 0.01-1 μM BaP and 0.1-10 μM Cd. A significant increase in the expression of genes coding for BaP metabolizing enzymes (CYP1A1, CYP1B1) occurred in a dose and time dependent manner at 3, 6, and 24 h post exposure. Likewise, a significant increase in the heavy metal responsive gene MT2A was observed following exposure to Cd. The EROD activity assay confirmed significant increases in CYP1(A/B) activity after 24 h of exposure to BaP which was not affected by the presence of Cd. Co-exposure to low concentrations of Cd and BaP were consistent with changes in gene expression as seen with single-compound exposures. These experiments are the first to provide information regarding toxicological responses in the RPTEC/TERT1 cell line that model those of the target tissue. We conclude that these cells can provide a useful tool for future toxicological studies.