Date

2017

Author

Çöpoğlu, Hülya

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Boron is a widely available element found in the earth’s crust. It is an essential micronutrient for plants and it is also beneficial for animals. At high concentrations boron is known to have toxic effects on cells, and currently the mechanism of this toxicity is still not documented. Liver, kidney, central nervous system, and gastrointestinal track were the most effected organs. Humans mostly exposure to boron as borates or boric acid. The exposure typically occurs through ingestion of food or water, through use of pesticides containing boron compounds, inhalation of boron-containing powders and dusts, or use of boron from cosmetics or medical preparations. Boron is metabolized into boric acid in the liver, which accumulates mainly in the liver, and in the excretory system organs. In this study we examined the boric acid metabolism and toxicity in hepatocellular carcinoma, HepG2 cells. In order to find the threshold for the toxic concentration HepG2 cells were treated between 0,5-40 mM of boric acid for 24 h and IC50 value was calculated as 24 mM. At this concentration, significant increase in DNA fragmentation and micronucleus formation were observed with single cell gel electrophoresis (Comet assay) and cytokines block micronucleus assay (CBMN). The genotoxicity results indicated that the DNA damage participated in the mechanism of boric acid toxicity, also the results of cell survival assay also revealed that, the cell viability were significantly inhibited by boric acid in a dose dependent manner. Gene expression analysis is performed by using Affymetrix Gene Chip Human Gene 1.0 ST Array platforms. Boric acid at IC50 concentration exposure significantly altered the expression of 828 genes in total, 467 were down-regulated and 361 were up-regulated. Database for Annotation, Visualization and the Integrated Discovery (DAVID) is used for the annotation and biological interpretations of the regulated genes. Pathway Analysis revealed that, the top networks that are altered by acute exposure of boric acid were cell cycle, the DNA replication and the steroid biosynthesis networks. Overall we have shown that at toxic concentrations exposure to boric acid results in DNA damage, effecting the regulation of genes that have role in cell cycle, DNA replication, and steroid biosynthesis. Further investigation of the differentially regulated genes identified in the study is planned for understanding the molecular mechanisms of boric acid toxicity in mammalian cells.  

Subject Keywords

Cytokines., Boric acid., Liver, Liver metastasis., Cell-mediated cytotoxicity.

URI

http://etd.lib.metu.edu.tr/upload/12621338/index.pdf
https://hdl.handle.net/11511/26731

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Graduate School of Natural and Applied Sciences, Thesis