Korean Journal of Nephrology 2002;21(1):12-19.
원저 : 2 , 3 , 7 , 8 - tetrachlorodibenzo - p - dioxin 이 배양 사구체 혈관간세포와 세뇨관 상피세포의 활성화에 미치는 영향 (Original Articles : Effects of 2 , 3 , 7 , 8 - tetrachlorodibenzo - p - dioxin ( TCDD ) on Glomerular Mesangial and Tubular Epithelial Cell Activation)
김은나(Eun Na Kim),유미라(Mi Ra Yu),임현진(Hyun Jin Lim),황의원(Eui Won Hwang),하헌주(Hun Joo Ha),이희발(Hi Bahl Lee)
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 μM) 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 μM 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. (Korean J Nephrol 2002;21(1):12-19)
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