ABSTRACT
<p><b>OBJECTIVE</b>Study on the promoter effects of sodium butyrate in high or low dosages on carcinogenesis process, based on the immortalization of human fetal esophageal epithelium induced by human papillomavirus (HPV) 18E(6)E(7) genes.</p><p><b>METHODS</b>The immortalized esophageal epithelium SHEE was treated with high concentration of the sodium butyrate (80 mmol/L) and then with low concentration (5 mmol/L) for 8 weeks respectively. The cells were cultured continuously without sodium butyrate for 14 weeks. The morphology, proliferation and apoptosis of the cells were studied by phase contrast microscopy, immunohistochemistry and flow cytometry. The dead and the viable cells were assayed by fluorescent microscopy with Hoechst 33342 and Propidium iodide staining. Tumorigenesis of the cells was assessed by soft agar colony formation and by transplantation of cells into nude mice and SCID mice.</p><p><b>RESULTS</b>When cells were exposed to high concentration of sodium butyrate, cell death was increased leaving few live cells. When cells were cultured in the medium with low concentration of sodium butyrate, the first proliferative stage appeared. Removal of the butyrate caused the cell to enter a crisis stage with a long doubling time resembling senescent cells. After the crisis stage, the cells progressed to the second proliferation stage with continuous replication and atypical hyperplasia. At the end of the second proliferative stage, carcinogenesis of the cells appeared with large colonies in soft-agar and tumor formation in transplanted SCID mice and nude mice.</p><p><b>CONCLUSIONS</b>The malignant change of the immortalized epithelium by the effects of sodium butyrate is the consequence of a two-stage mortality mechanism: cells death by butyrate cytotoxicity and cell crisis by abrogation of sodium butyrate. These data reveal that in high dosage, sodium butyrate induces cell death and in low dosage, it induces cell proliferation, which emphasizes the importance of butyrate as a promotor of carcinogenesis.</p>
Subject(s)
Animals , Humans , Mice , Butyrates , Toxicity , Carcinogens , Toxicity , Cell Death , Cell Division , Cell Line, Transformed , Cell Transformation, Neoplastic , Esophageal Neoplasms , Esophagus , Pathology , Mice, Inbred BALB C , Papillomaviridae , VirulenceABSTRACT
<p><b>OBJECTIVE</b>To study the effect of selenium (Se) and iodine (I) and the compound of both on the proto-oncogenes c-fos and c-jun mRNA and their protein expression in the cultured rat hippocampus neurons.</p><p><b>METHODS</b>Using the technique of serum free hippocampus neuron culture, different doses of Se and I and Se + I compound were added into the medium. The expression of the mRNA of c-fos, c-jun in hippocampus neurons cultured for 1, 3, 5, 7 and 10 d were studied using both in situ hybridization and SABC immunohistochemical technique.</p><p><b>RESULTS</b>Both Se and I could enhance the expression of c-fos, c-jun mRNA and their proteins, especially the combination of I and Se able to give a remarkable effect on c-jun mRNA expression.</p><p><b>CONCLUSIONS</b>Se and I may effect the expression of both c-fos and c-jun mRNA, especially the c-jun mRNA and its protein of hippocampus neurons, and thus may effect the differentiation and development of neurons.</p>
Subject(s)
Animals , Rats , DNA-Binding Proteins , Metabolism , Hippocampus , Metabolism , Iodine , Neurons , Metabolism , Proto-Oncogene Proteins c-fos , Metabolism , Proto-Oncogene Proteins c-jun , Metabolism , RNA, Messenger , Metabolism , SeleniumABSTRACT
To investigate the role of Egr-1 in the carcinogcnestic process of hepatocellular carcinoma (H-CC). Methods Expression of Egr-1 gene in HCC tissues were detected by in situ hybridization and immunohistochemistry. Human breast andmouse liver and brain tissues were used for control. ResultsLittle or no Egr-1 transcription was detected both in HCC tissues and in their normal counterparts. High transcription of Egr-1 was detected in the LCD and atrophic-like liver plate of HCC tissues. Protein expression of Egr-1 gene was consistent with mRNA transcription. High expression of Egr-1 protein was also detected in normal breast and mouse brain tissues. ConclusionsLittle or no expression of Egr-1 may play a role in the deregulation of normal growth in the carcinogenestic process of HCC. The differences of Egr-1 expression among liver cells, breast epithelia and mouse brain tissues might be associated with their different ways of proliferation and differentiation in different cell types.