ASSESSMENT OF CELL-SPECIFIC CYTOTOXIC RESPONSES OF THE KIDNEY TO SELECTED AROMATIC-HYDROCARBONS

The present studies were conducted to assess cell-specific cytotoxic responses of the kidney to selected aromatic hydrocarbons (AHs) using in vitro culture systems of glomerular mesangial cells and cortical tubular epithelial cells. Primary cultures of glomerular mesangial cells or cortical tubular epithelial cells were treated for 24 hr with naphthalene (NAPH, 0.1-1000 mu M), 2-methylnaphthalene (2-MNAPH, 0.1-1000 mu M), benzo[a]pyrene (B[a]P, 0.3-300 mu M), pentachlorophenol (PCP, 0.1-1000 mu M), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 0.001-1 nM) or 2,3,7,8-tetrachlorodibenzofuran (TCDF, 0.005-5 nM). [H-3]Thymidine incorporation into DNA, cellular potassium content, and lactate dehydrogenase (LDH) leakage were used as indices of cytotoxicity. Glomerular mesangial cells exposed to NAPH or 2-MNAPH (0.1-1000 mu M) exhibited [H-3]thymidine incorporation profiles similar to those of the vehicle controls, whereas B[a]P at all concentrations and PCP at 1000 mu M decreased [H-3]thymidine incorporation in comparison with the controls. TCDD and TCDF increased [H-3]thymidine incorporation relative to controls at 0.1 nM and 0.5 nM, respectively. Glomerular mesangial cells treated with NAPH or PCP exhibited decreased cellular potassium content and increased LDH leakage only at the 1000 mu M concentration. In tubular epithelial cells, treatment with NAPH (10 or 1000 mu M), 2-MNAPH (10 or 1000 mu M), B[a]P (300 mu M), and PCP (10 or 1000 mu M) induced concentration-dependent decreases in [H-3]thymidine incorporation relative to controls. In contrast, exposure of tubular epithelial cells to TCDD or TCDF did not modulate [H-3]thymidine incorporation at any of the concentrations tested. A modest decrease in cellular potassium content and an increase in LDH leakage was observed at the 1000 mu M concentration of PCP in tubular epithelial cells. On the basis of these data, we conclude that renal glomerular mesangial cells and tubular epithelial cells exhibit differential cytotoxic response profiles to AHs.