http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
EMT-6 세포에서 유기수은의 세포독성에 대한 sulfhydryl 화합물의 역할
김공호,염정호,이미애 의과학연구소 1998 全北醫大論文集 Vol.22 No.2
In present study, we evaluated the effects of sulfhydryl compounds on the cytotoxicity of methylmercury chloride (CH_3HgCl) in EMT-6 cells. Methylmercury chloride was shown to decrease nitric oxide (NO) and cellular ATP production in EMT-6 cells. The compounds investigated were glutithione (GSH), L-cystein (Cys), dithiothreitol (DTT), oxithiazolidine-4-carboxyl acid (OTC) and buthionine sulfoximine (BSO). These compounds were not toxic under 0-400 μM conditions. in the condition of 5 μM CH_3HgCl, BSO decreased NO_2 and ATP production in dose-dependent manner and OTC showed no effects. GSH, Cys and DTT in-creased NO_2 and ATP production in dose-dependent manner. These compounds probably had protective effects on mercury-induced cytotoxicity. We evaluated the effects of intracellular sulfhydryl compound level on mercury-induced cytotoxicity dby the pretreatment experiments. Pretreatment with GSH or Cys did not changed NO_2 and ATP production andpretreatment of BSO was decreased in dose- and time-dependent manner. Pretreatment with DTT, OTC increased NO_2 and ATP production in dose- and time-dependent manner. The protective effects of DTT on mecury-induced cytotoxicity were more prominent than OTC. These results indicated that sulfhydryl compounds had the protective effects against mercury-induced cyto-toxicity by increasing the intracellular sulfhydryl compound levels. (Key Words : methylmercury chloride, GSH, NO, sulfhydryl compounds)
RAW264.7 세포주를 이용한 수은화합물의 세포독성기전에 관한 고찰
김공호,고대하,소병율 大韓産業醫學會 1996 대한직업환경의학회지 Vol.8 No.3
Balb/c 마우스의 복강내에 Abelson leukemia virus(A-MuLV)를 주입하여 발생시킨 종양의 복수에서 기원한 RAW264.7 cell line을 배양하는 조건에 여러농도의 수은을 첨가하여 nitrite와 ATP 생성의 변화를 관찰한 결과는 다음과 같다. 수은화합물을 첨가한 배양조건에서 RAW264.7세포의 생존률은 mercury chloride의 경우는 0.8μM이하, methyl mercury chloride의 경우 0.4μM이하의 농도에서는 95% 이상으로 유지되었으며, 그 이상의 농도에서는 생존률이 현저히 감소되었다. 이때 ATP 및 nitrite의 생성능은 수은화합물의 농도증가에 따라 용량의존적으로 감소되었다. 배양액(DMEM)에 4.5g/ℓ의 glucose를 1배에서 5배를 추가하여 농도를 강화시킨 조건에서 RAW264.7 세포를 48시간동안 배양하면 ATP 및 nitrite 생성량은 전반적으로 1배 추가시 가장 많은 양이 생성되었고 배양액의 pH는 1배 추가시 6.7-6.8의 범위로 감소하였다가 glucose 농도 증가에 따라 대조군과 비슷한 7.2까지 증가하였다. 이때 세포의 생존률은 모든 군에서 95%이상으로 유지되었다. 그리고 배양액의 glucose 농도를 2배로 강화시킨 실험조건(배양액내 glucose 기준농도의 1배를 더 첨가한 경우)에서는 mercury chloride 및 methylmercury chloride의 농도를 증가시켰음에도 불구하고 ATP 및 nitrite 생성량은 감소되지 않고 대조군과 비슷한 값으로 유지되었다. 이상의 결과는 수은이 면역세포의 nitric oxide 생성을 저해하는 것은 세포내 ATP생성과 관련한 대사과정, 특히 구연산회로(citric acid cycle)의 억제를 통해 발휘된다는 것을 시사하고 있다. The effects of glucose on the productions of ATP and nitrite which are inhibited by mercury compounds, were examined in a cell culture system of RAW 264.7 cells. The cells were cultured in Dulbecco's Modified Eagle's medium(DMEM) with cytokines, IL-1 and TNF for 24 hours. The viability of RAW 264.7 cells at the end of culture was significantly decreased by mercury chloride or methylmercury chloride added into the media in dose-dependent manner, however the viability of RAW 264.7 cells were influenced in the concentrations less than 0.8μM of mercury chloride or 0.4μM of methylmercury chloride. The addition of 4.5g/l glucose to normal DMEM lowered the pH of media to the range of 6.7-6.8 after 48 hours of culture, but not for the cell survivals. This supplement of glucose to the media also prevented the inhibitions of ATP and nitrite syntheses which were caused by mercurial compounds. These results suggest that the disorder of cell mediated immunity by mercurials could be related to the inhibition of nitric oxide synthesis which seems to be caused by the inhibition of ATP synthesis, especially related to the citric acid cycle.