The RPTEC/TERT1 Cell Line as an Improved Tool for In Vitro Nephrotoxicity Assessments.

ABSTRACT

In earlier studies, we have characterized a newly developed cell line derived from the renal proximal tubule epithelial cells (RPTEC) of a healthy human male donor in order to provide an improved in vitro model with which to investigate human diseases, such as cancer, that may be promoted by toxicant exposure. The RPTEC/TERT1 cell line has been immortalized using the human telomerase reverse transcriptase (hTERT) catalytic subunit and does not exhibit chromosomal abnormalities (Evercyte Laboratories). We have previously conducted single-compound and binary mixture experiments with the common environmental carcinogens, cadmium (Cd), and benzo[a]pyrene (B[a]P). Cells exhibited cytotoxic and compound-specific responses to low concentrations of B[a]P and Cd. We detected responses after exposure consistent with what is known regarding these cells in a normal, healthy kidney including significant gene expression changes, BPDE-DNA adducts in the presence of B[a]P, and indications of oxidative stress in the presence of Cd. The RPTEC/TERT1 cell line was also amenable to co-exposure studies due to its sensitivity and compound-specific properties. Here, we review our earlier work, compare our findings with commonly used renal cell lines, and suggest directions for future experiments. We conclude that the RPTEC/TERT1 cell line can provide a useful tool for future toxicological and mixture studies.