Premalignant alteration assessment in liver-like tissue derived from embryonic stem cells by aristolochic acid I exposure.
Premalignant alteration assessment in liver-like tissue derived from embryonic stem cells by aristolochic acid I exposure.
复制标题
马兜铃酸 I 暴露对胚胎干细胞来源的肝样组织的癌前改变评估
DOI：
10.18632/oncotarget.12424
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发表时间：
2016-11-29
期刊：
影响因子：
--
通讯作者：
Lou YJ
中科院分区：
文献类型：
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作者：
Li T;Jin K;Zhu DY;Li L;Mao ZR;Wu BW;Wang YF;Pan ZF;Li LJ;Xiang CS;Su KK;Lou YJ
迄今为止，尚未建立基于肝脏偏好的化学致癌性体外预测评价。在这里，我们报告了一种新的方法来调查致癌物马兜铃酸I（AAI）在小鼠胚胎干细胞来源的肝样组织中引发的癌前事件。AAI暴露后，肝脏样组织表现出旁分泌白细胞介素-6表型特征。肝细胞平行表达STAT 3/p-STAT 3、c-Myc和Lin 28 B。部分细胞表现出脱分化特征，如充满甲胎蛋白颗粒，体积增大，核质穿梭等。当这些细胞注射到小鼠体内时，异种移植物大多显示出具有恶性核的均匀的肝样组织区域。肝恶性肿瘤标志物甲胎蛋白、细胞角蛋白7和细胞角蛋白19分别在白蛋白阳性区域共同表达。总之，我们建立了一个方法来预测致癌物AAI引发的肝脏易感性。该系统可用于评价潜在致癌物对肝脏的影响，并可用于药物抗肝癌作用的体外筛选。
The in vitro predictive evaluation of chemical carcinogenicity based on hepatic premalignance has so far not been established. Here, we report a novel approach to investigate the premalignant events triggered by human carcinogen aristolochic acid I (AAI) in the liver-like tissue derived from mouse embryonic stem cells. By AAI exposure, the liver-like tissue exhibited the paracrine interleukin-6 phenotypic characteristics. Hepatocytes expressed STAT3/p-STAT3, c-Myc and Lin28B in parallel. Some of them displayed the dedifferentiation characteristics, such as full of α-fetoprotein granules, increase in size, and nucleocytoplasmic shuttle of Oct4. When these cells were injected into mice, the xenografts mostly displayed the uniform area of hepatic-like tissue with malignant nuclei. The hepatic malignant markers, α-fetoprotein, cytokeratin 7 and cytokeratin 19, were co-expressed in albumin-positive areas, respectively. In conclusion, we established an approach to predict the hepatic premalignance triggered by carcinogen AAI. This premalignant assay system might aid to evaluate the effects of potential carcinogens in liver, and probably to screen the protecting against hepatocarcinogenic efficacy of pharmaceuticals in vitro.