Original Article
Induction of hepatocellular carcinoma in B6C3 (F1) mice chronicly exposed to trichloroethylene with enhanced acetylation of histone H2AK9ac and SET expression in the liver tissue
Li Shenpan, Chang Qunqun, Ren Xiaohu, Luo Nuanyuan, Huang Haiyan, Wu Desheng, Liu Yungang, Liu Jianjun
Published 2021-12-20
Cite as Chin Ind Hyg Occup Dis, 2021, 39(12): 910-914. DOI: 10.3760/cma.j.cn121094-20201009-00562
Abstract
ObjectiveTo establish an animal model of trichloroethylene (TCE) -induced liver cancer following chronic exposure and to understand the changes in SET expression and histone acetylation, potentially serving as a molecular mechanism for TCE-induced hepatocarcinogenesis.
MethodsB6C3 mice at 6 weeks were treated with TCE at a series of doses (500, 1000 and 2000 mg/kg) by gastric gavage, with corn oil used as the negative control and carbon tetrachloride (CCl4) as the positive control. The serum and liver were sampled for the determination of biochemical indexes and pathological examination after 56 weeks of chemical exposure. Western blot was used to determine the levels of SET, H2AK9ac and HDAC1 expression.
ResultsThe overall survival rate of the mice in various groups was 90.4% (141/156) , with no statistical difference between groups (P>0.05) . Compared with the negative control, the organ coefficient for the liver in the high dose TCE group and the positive control group were significantly increased (P<0.05) . The levels of ALT, AST, LDH and BUN in the all the three TCE groups and the positive control were significantly higher than those in the negative control (P<0.01) . CREA levels in the 1000 and 2000 mg/kg TCE groups were significantly higher than those in the negative control (P<0.05) . Statistical increases in the incidence of hepatocellular carcinoma and the activities of ALT and AST in various doses of TCE-exposed mice as compared with the control were observed (P<0.01) , in a dose-dependent manner. In the 1000 and 2000 mg/kg of TCE treated mice, levels of SET and H2AK9ac were increased (P<0.05) , while HDAC1 was decreased (P<0.05) , Compared to the tissue adjacent to liver cancer, in the 1000 and 2000 mg/kg TCE groups, the levels of SET were increased (P<0.05) , while HDAC1 was decreased (P<0.05) , and H2AK9ac increased in the 2000 mg/kg group.
ConclusionThe hepatocellular carcinoma mouse model induced by chronic exposure to trichloroethylene was successfully established, with enhanced SET protein expression and H2AK9ac in the hepatic tissue.
Key words:
Trichloroethylene; Animal model of liver cancer; Histone modification
Contributor Information
Li Shenpan
Southern Medical University, School of Public Health Guangzhou, Guangzhou 510515, China
Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China
Chang Qunqun
Southern Medical University, School of Public Health Guangzhou, Guangzhou 510515, China
Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China
Ren Xiaohu
Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China
Luo Nuanyuan
Southern Medical University, School of Public Health Guangzhou, Guangzhou 510515, China
Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China
Huang Haiyan
Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China
Wu Desheng
Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China
Liu Yungang
Southern Medical University, School of Public Health Guangzhou, Guangzhou 510515, China
Liu Jianjun
Southern Medical University, School of Public Health Guangzhou, Guangzhou 510515, China
Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China
本文中补充“通信作者：刘云岗：E-mail: yungliu@126.com；刘建军：E-mail: junii8@126.com。 基金项目：国家自然科学基金面上项目（81872666）；深圳市医学重点学科建设经费资助（SZXK069）；深圳市医疗卫生三名工程项目（SZSM201611090）”。