A study about the effect of myeloperoxidase on tamoxifen used in breast cancer treatment

?Myeloperoxidase-H202-Cl-? system has a potent antibacterial and cytotoxic effect in leucocytes. In physiological pHs, myeloperoxidase leads to the production of hazardous reactive oxygen species together with the oxidation of Cl- to Cl+. Under physiological conditions, if the balance between production and detoxification mechanisms of ROS is imbalanced, then some damages may occur in human body. Accumulation of oxidative damage in a cell causes radical-related damage to DNA, to proteins and to lipids and plays a key role in the development of age-dependent diseases such as cancer and neurodegenerative disorders.In this thesis, reaction products formed by the effect of myeloperoxidase-H202-Cl- system on Tamoxifen, were studied. For this purpose, leucocytes found in human blood samples were isolated succesfully. The effect of the purified myeloperoxidase obtained from leucocytes which was isolated by lysis formerly, on Tamoxifen at 37°C and in physiological pH (pH 7.2-7.3) was evaluated by using UV-Vis. spectrophotometer and LC-MS, FT-IR spectrometer systems.In previous studies, metabolite formation by the effect of liver microsomes on Tamoxifen and Horseradish peroxidase catalysis was examined. In this study, the very first obtained myeloperoxidase at sufficient quantities and its usage at higher concentrations, provided to monitor products distinctly which were formed in consequence of enzyme acting on Tamoxifen. It was decided that free radicals were formed as a result of broken C-O-C etheral bond, C=C double bond and C-N bond found in Tamoxifen structure.