Cytochrome P450 And Anticancer Drug Metabolism

Background Cytochrome P450 (CYP450) is an important enzyme for metabolizesmany xenobiotics and endogens. The relationship between the metabolism of chemicals and CYP450 function has become an essential part for drug safety evaluation. It helps in predicate drug-drug interactions and provides information on drug metabolism and transformation process. The polymorphisms of CYP450 bring complex factors to disease occurrence rules and individualized drug treatment design. CYP450 with other active drug metabolism enzyme play a whole picture in metabolism and transformation of chemicals.Objectives The main part emphasized on the relationship between CYP450 and themetabolism of novel anticancer reagent para-toluene-sulfonamide (PTS). The investigated aspects include CYP450 function, the modulatory effect of the drugs on CYP450, mechanism of CYP inhibitors ect. Besides, the thesis also designed to compare the differences among rat liver, human normal liver tissue and human liver tumor tissue on aspects of whole CYP450 activity, CYP450 isoforms activities, flavin-containing monooxygenase activity, glutathione S-transferases activity, the content of microsome fraction protein , content of cytosolic fraction protein and so on.Methods Rat liver perfusion, in vitro microsome incubation, high performance liquid chromatography (HPLC) analysis of substrates and metabolites, inhibition screening...