title: The RPTEC/TERT1 cell line models key renal cell responses to the environmental toxicants, benzo[a]pyrene and cadmium.
abstract: We have characterized initial canonical responses to two environmental toxicants, cadmium (Cd) and benzo[a]pyrene (B[a]P), in a novelin vitromodel 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 B[a]P, known or suspected renal toxicants respectively. Cells exhibited cytotoxicity to concentrations of B[a]P 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 B[a]P and 0.1-10 μM Cd. A significant increase in the expression of genes coding for B[a]P 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 B[a]P which was not affected by the presence of Cd. Co-exposure to low concentrations of Cd and B[a]P 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.
authors.affiliation: Graduate Program in Biomedical Sciences, School of Medicine, Tulane University, New Orleans, LA 70112, United States of America ; Department of Global Environmental Health Sciences, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, United States of America.
authors.forename: B R
authors.initials: BR
authors.lastname: Simon
authors.affiliation: Department of Global Environmental Health Sciences, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, United States of America.
authors.forename: M J
authors.initials: MJ
authors.lastname: Wilson
authors.affiliation: Department of Global Environmental Health Sciences, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, United States of America.
authors.forename: J K
authors.initials: JK
authors.lastname: Wickliffe
keywords: Benzo[a]pyrene; Cadmium; In vitro immortalized renal cell; RPTEC/TERT1; Tox21