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The Role Of Reactive Oxygen Species In Cell Death Induced By Thymidylate Synthase Inhibitors, Ufuk Ozer

Theses and Dissertations

Thymidylate synthase (TS) catalyzes the reductive transfer of a methyl group from N5,N10-methylenetetrahydrofolate (CH₂-THF) to dUMP, forming dTMP and dihydrofolate (DHF). It is generally accepted that inhibition of the enzyme leads to a deficiency of dTMP, followed by genome damage and programmed cell death. As such, TS has long been viewed as an important target of anti-neoplastic agents, such as 5-fluorouracil (5-FU) and raltitrexed (RTX), which lead to inhibition of the enzyme. Oxidative stress is well-recognized as having a central role in cellular response to a number of DNA damaging agents, and may be a proximate cause of …