采用微团培养模型探讨染料木黄酮的发育毒性  被引量:7

The developmental toxicity of genistein in micromass culture

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作  者:肖杨[1] 刘然[1] 邢丽娜[1] 尚兰琴[1] 许雅君[2] 郝卫东[1] 

机构地区:[1]北京大学公共卫生学院毒理学系,北京100191 [2]北京大学公共卫生学院营养与食品卫生学系,北京100191

出  处:《癌变.畸变.突变》2010年第4期271-275,共5页Carcinogenesis,Teratogenesis & Mutagenesis

基  金:国家自然科学基金(30771821);国家"十一五"科技支撑计划(2006BKA02A02)

摘  要:目的:利用大鼠胚胎肢芽和中脑细胞微团培养模型研究染料木黄酮(genistein,GEN)的发育毒性,并探讨其发育毒性机制。方法:实验分为不同浓度的GEN(0、0.94、1.875、3.75、7.5、15.0μg/ml)染毒组,受试物分别作用于培养大鼠胚胎肢芽细胞和中脑细胞微团,采用中性红摄取法检测GEN对细胞增殖的影响,采用阿利新蓝染色方法检测GEN对肢芽细胞分化的影响,采用图像处理分析方法检测GEN对中脑细胞分化的影响。计算细胞50%增殖抑制浓度(IC50_P)和50%分化抑制浓度(IC50_D)。用不同浓度的雌激素受体拮抗剂ICI182780(0.1,0.5,1μmol/L)分别预处理细胞后再加入GEN(7.5μg/ml),观察雌激素受体途径在GEN诱导的发育毒性中的作用。结果:GEN对肢芽细胞的IC5_0P和IC5_0D分别为5.4μg/ml和4.9μg/ml,GEN对中脑细胞的IC5_0P为6.2μg/ml,IC5_0D分别为7.1μg/ml(集落分化个数)或5.3μg/ml(集落分化面积)。IC5_0P/IC50_D的比值均接近1。在GEN7.5μg/ml染毒组,用ICI182780预处理细胞,不能改变GEN诱导的发育毒性作用。结论:根据Flint's和欧洲替代方法验证中心ECVAM致畸物判别标准,并结合人体实际可能接触水平,认为GEN为强致畸物,并且对人类存在可能的风险。其致畸作用可能主要通过细胞毒性发挥作用,不依赖于雌激素受体途径。OBJECTIVE:To explore the developmental toxicity of genistein(GEN)by micromass cultures of rats limb bud(LB)and midbrain(MB)cells,and investigate its possible mechanisms.METHODS:Micromass cultures of LB and MB were exposed to GEN with a series of concentrations(0,0.94,1.875,3.75,7.5 and 15 μg/ml).The effect of GEN on cell proliferation was detected by neutral red uptake;the effect of GEN on LB and MB differentiation was assessed by Alcian Blue Staining and Image Analysis,respectively.Cell cultures were pretreated by ICI182780(0.1,0.5 and 1 μmol/L),and then with GEN(7.5 μg/ml)added,in order to observe the role of estrogen receptor pathway in the developmental toxicity induced by GEN.RESULTS:For micromass cultures of LB,IC50-P(cell proliferation)and IC50-D(cell differentiation)of GEN were 5.4 μg/ml and 4.8 μg/ml,respectively.For micromass cultures of MB,they were 6.2 μg/ml and 7.1 μg/ml(differentiation judged by number of foci)/5.3 μg/ml(differentiation judged by area of foci),respectively.The ratio IC50-P/IC50-D all approximated to 1.The developmental toxicity induced by GEN with 7.5 μg/ml could not be changed by ICI182780 pre-treatment.CONCLUSION:According to the discrimination rules of Flint and European Center for the Validation of Alternative Methods(ECVAM),and in the light of the human exposure level,GEN was regarded as a strong teratogen,with potential risk toward human.The results indicated that the developmental toxicity GEN may not be mediated by estrogen receptor(ER)pathway.

关 键 词:染料木黄酮 微团培养 发育毒性 雌激素受体 

分 类 号:R994.4[医药卫生—毒理学]

 

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