Premalignant alteration assessment in liver-like tissue derived from embryonic stem cells by aristolochic acid I exposure

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 e...

Full description

Saved in:
Bibliographic Details
Published in:Oncotarget 2016-11, Vol.7 (48), p.78872-78882
Main Authors: Li, Tong, Jin, Ke, Zhu, Dan-Yan, Li, Lu, Mao, Zheng-Rong, Wu, Bo-Wen, Wang, Yi-Fan, Pan, Zong-Fu, Li, Lan-Juan, Xiang, Chun-Sheng, Su, Kun-Kai, Lou, Yi-Jia
Format: Article
Language:English
Subjects:
Albumins - metabolism
alpha-Fetoproteins - metabolism
Animals
Aristolochic Acids - toxicity
Biomarkers, Tumor - metabolism
Cell Dedifferentiation - drug effects
Cell Line
Cell Transformation, Neoplastic - chemically induced
Cell Transformation, Neoplastic - metabolism
Cell Transformation, Neoplastic - pathology
DNA-Binding Proteins - metabolism
Dose-Response Relationship, Drug
Hepatocytes - drug effects
Hepatocytes - metabolism
Hepatocytes - pathology
Interleukin-6 - metabolism
Keratin-19 - metabolism
Keratin-7 - metabolism
Liver Neoplasms - chemically induced
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Mice
Mouse Embryonic Stem Cells - drug effects
Mouse Embryonic Stem Cells - metabolism
Mouse Embryonic Stem Cells - pathology
Paracrine Communication - drug effects
Precancerous Conditions - chemically induced
Precancerous Conditions - metabolism
Precancerous Conditions - pathology
Proto-Oncogene Proteins c-myc - metabolism
Research Paper
Signal Transduction - drug effects
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.12424