Korean J Nephrol.  2002 Jan;21(1):12-19.

Effects of 2,3,7,8-tetrachlorodibenzo- p-dioxin(TCDD) on Glomerular Mesangial and Tubular Epithelial Cell Activation

• Kim EN
• Yu MR
• Lim HJ
• Hwang EW
• Ha HJ
• Lee HB

Abstract

BACKGROUND: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a prototype compound of polyhalogenated aromatic hydrocarbons, produces diverse biologic effects. Although nephrotoxicity of aromatic hydrocarbons such as benzo[a]pyrene(BP) is well known, little is known about the effects of TCDD on renal function. Thus, the present study examined the effects of TCDD on cell viability, proliferation, and extracellular matrix(ECM) synthesis by glomerular mesangial cells, LLC-PK1 cells representing proximal tubular epithelial cells, and MDCK cells representing distal epithelial cells and compared with the effects of BP.
METHODS
Quiescent cells were incubated with serum free media containing different concentrations of TCDD(1-100 nM) and BP(3 and 30 micro M) for 24- 96 hours. Cell viability and proliferation were assessed by lactate dehydrogenase(LDH) release and [3H]-thymidine incorporation, respectively. Secreted fibronectin was measured by Western blot analysis.
RESULTS
When cells were continuously exposed to TCDD, LDH release significantly increased in MMC, LLC-PK1, and MDCK in a dose- and a time- dependent manner. [3H]-Thymidine incorporation was increased in MMC and LLC-PK1 but decreased in MDCK by TCDD. Contrary to TCDD, 30 micro BP significantly inhibited [3H]-thymidine incorporation in MMC and MDCK but not in LLC-PK1. Both TCDD and BP increased fibronectin secretion by MMC, LLC-PK1, and MDCK cells, suggesting that TCDD and BP may cause renal fibrosis leading to loss of renal function.
CONCLUSION
These data provide experimental evidence that TCDD can alter cell viability and proliferation and increase ECM synthesis by renal cells which may lead to renal injury.

Keyword

Tetrachlorodibenzo-p-dioxin; Cell viability; Proliferation; Mesangial cell; Tubular epithelial cell

MeSH Terms

Animals
Blotting, Western
Cell Survival
Culture Media, Serum-Free
Epithelial Cells*
Fibronectins
Fibrosis
Hydrocarbons, Aromatic
Lactic Acid
LLC-PK1 Cells
Madin Darby Canine Kidney Cells
Mesangial Cells
Swine
Tetrachlorodibenzodioxin
Culture Media, Serum-Free
Fibronectins
Hydrocarbons, Aromatic
Lactic Acid
Tetrachlorodibenzodioxin