Low dose demethylating agents in oral cancerAndThe respiratory phenotype of Phd1 -/- mouse liver mitochondria

[摘要] Project 1: DNA methylation is a gene silencing mechanism, the pattern of which is often disrupted in cancer. 5-Aza2’ deoxycytidine (DAC) is a demethylating agent used in the treatment of haematological malignancies with research suggesting that the treatment may be transferable to solid tumours. High doses have proved toxic however low doses may provide the benefits of demethylation without the toxic side effects. In this project I examined the effects of various concentrations of DAC on two oral cancer cell lines; Vu40T cells but not Scc040 cells . Furthermore DAC treatment lead to an increase in 5-hydroxymethycytosine in both cell lines and a corresponding increase in TET2 gene expression. Project 2: Hypoxia inducible factor (HIF) is the master regulator of the hypoxia response. Prolyl hydroxylase domain proteins (PHDs) control of the stability of the alpha subunit in an oxygen dependent process. Phd1 \(^-\)\(^/\) \(^-\) mice produce more ATP through glycolsis and consume less oxygen. This project showed loss of Phd1 altered the activity of complexes I-IV in mouse liver mitochondria in a highly variable manner suggesting that the pathway from Phd1 knockout to respiratory complex decline is not linear.

[发布机构] University:University of Birmingham;Department:School of Clinical and Experiment Medicine, Department of Medicine and Medical Education

[关键词] R Medicine;R Medicine (General)