ABSTRACT
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.
ABSTRACT
Objective@#To investigate DNA damage in the transformed human bronchial epithelial cells (16HBE) induced by hexavalent chromium (Cr6+) and further elucidate the potential carcinogenesis mechanism of Cr6+.@*Methods@#16HBE were treated with different concentration of Cr6+ (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 Cr6+-treated cells in soft agar showed significant increases (p<0.05) . The 2.5 μmol/L Cr6+-treated cells also formed tumors subcutaneously in nude mice. Cr6+ 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 Cr6+.@*Conclusion@#The declined expression of 53BP1 may mediate Cr6+-induced DNA damage and further involved in the cell malignant transformation.