[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].

Objective: To 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. Methods: B6C3 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 (CCl(4)) 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. Results: The 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. Conclusion: The hepatocellular carcinoma mouse model induced by chronic exposure to trichloroethylene was successfully established, with enhanced SET protein expression and H2AK9ac in the hepatic tissue.

[Analysis of the potential role of SET in chromium-induced malignant transformation cells based on quantitative proteomics].

Objective: To investigate alteration of proteins profile in malignant transformation bronchial epithelial cells(16HBE-T) induced by hexavalent chromium[(Cr(VI))] and analyze the expression level of SET protein, then to provide some new insights for the carcinogenesis mechanism of Cr(VI). Methods: Total protein was extracted from 16HBE cells and was alkylated and desalinated before digested into peptides. The products were labeled with Tandem Mass Tag (TMT) and identified using LC-ESI-MS/MS. Results: A total of 3 517 proteins were found, expression differences greater than 1.5 or less 0.67 times were to found have 185 and 201 proteins, respectively. Gene enrichment analysis revealed that differential proteins were mainly involved in autophagy, DNA damage repair, RNA processing and other biological processes. Western blot results showed the expression level of SET was significantly increased while downregulated in histone H3K18/27 acetylation and p53 protein. Conclusion: Proteins involved in multiple biological processes altered in 16HBE-T cells and regulation mode of SET inhibiting histone H3K18/27 acetylation regulating transcriptional activity of p53 may paly an important role in Cr(VI)-association carcinogenesis.

[Studies on the DNA damage in the transformed bronchial epithelial cells induced by hexavalent chromium].

Objective: To investigate DNA damage in the transformed human bronchial epithelial cells (16HBE) induced by hexavalent chromium (Cr(6+)) and further elucidate the potential carcinogenesis mechanism of Cr(6+). Methods: 16HBE were treated with different concentration of Cr(6+ ()0, 0.625, 1.25, 2.5 µmol/L) for 15 weeks. The malignant degrees of transformed cells were identified by the assays for anchorage-independent growth and tumorigenicity. According to the single cell gel electrophoresis (SCGE) assay, the DNA damage rate was calculated. The expression level of 53BP1 was determined by Western blot. Results: Chromium-treated cells could form colonies in soft agar and tumors in nude mice. Compared with the control group, colony formation efficiency of 1.25µmol/L and 2.5 µmol/L Cr(6+)-treated cells in soft agar showed significant increases (p<0.05) . The 2.5 µmol/L Cr(6+)-treated cells also formed tumors subcutaneously in nude mice. Cr(6+) could cause different degree of DNA damage to 16HBE cells in a dose-dependent manner. In addition, Western blot analyses showed that 53BP1 was aberrantly down-regulated at 2.5 µmol/L dose and has no significant changes at 0.625 µmol/L and 1.25 µmol/L dose under the treatment of Cr(6+). Conclusion: The declined expression of 53BP1 may mediate Cr(6+)-induced DNA damage and further involved in the cell malignant transformation.