BORIC ACID INDUCED TRANSCRIPTOMIC CHANGES IN HEPG2 CELL LINE AT GROWTH INHIBITORY CONCENTRATIONS

Date

2023-3-31

Author

Tombuloğlu, Ayşegül

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Boron is a micronutrient with many physiological roles. Although high levels of in vitro exposure to boric acid (BA), the physiologically abundant form of Boron, have been associated with cytotoxicity in several studies, relatively little is known about the cytotoxic mechanisms of BA. Herein, the gene expression profiles of BA treatment of HepG2 cells at three growth-inhibitory concentrations, IC50, IC25, and IC12.5, were investigated with microarray technology. The analyses revealed key biological processes, pathways and regulatory processes elicited by in vitro BA treatment at growth-inhibitory doses. The pathway-level transcriptomic changes were consistent for all three levels of BA with some nuances. Regardless of the concentration, cell cycle and apoptosis were significantly overrepresented in the downregulated and upregulated lists of genes, respectively. These terms were less prominently enriched at the IC12.5 level. Furthermore, contrary to the higher concentrations, DNA repair was not significantly enriched at IC12.5. At all three concentrations, in vitro BA treatment stimulates a marked increase in the expression of UDP-glucuronosyltransferase genes. All transcriptomic profiles exhibited significantly altered metabolism, especially lipid/steroid metabolism, despite some subtle differences concerning concentration. BA-associated regulation events were investigated through network analyses at all concentrations. Overall, BA-induced transcriptomic changes at growth-inhibitory concentrations pointed toward a senescence-like fate with early-apoptotic markers. Deregulation of DNA repair processes was noticeable at higher doses and might be linked to concentration-dependent genotoxicity examined in a previous study.

Subject Keywords

Boric acid, Growth inhibition, Microarray, Network Analysis, HepG2

URI

https://hdl.handle.net/11511/103428

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Graduate School of Informatics, Thesis