Relation between DNA repair enzyme and anti-cancer agents

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The hematological malignancy is has been changed as a disease which reacts to the chemotherapy and can be expected to be cure. However the existence of the recurrence case and the primary resistance is the important problem. We have so far made the examinations about the resistance mechanisms and its conquest by establishing various drug resistance cell lines.The multi-drug resistance and acquisition resistance are important problems clinically, and we are considering relation by the DNA repair gene (Ref-1/APE and topoisomerase I) and anti-cancer agent resistance in this study.The cloning of DNA damage repair gene Ref-1/APE was performed using the rtPCR method. This DNA was included in the vector and transfected into the human leukemia cell line K562. This over-expressed Ref-1 is combined with the fluorescence protein GFP. Therefore it was detected under the confocal microscope that GFP-ref1 fusion protein was mainly discovered in the nucleus of K562 after transfection. Moreover, it al … More so detected that fusion protein was over-expressed using Western blotting methods. The susceptibility of various anti-neoplasm agents was examined, and the susceptibility enhancement effect was seen in the camptothecin which is known topoisomerase I inhibitor. The increase of deavable complexes of topoisomerase I and DNA was existed, and it was considered as one of the mechanism of susceptibility increase. Camptothecin which inhibit topoisomerase I as target enzyme showed cross-resistance with arsenic trioxide in a topoisomerase I deficit and mutation cell lines. There is no difference in the increase of the oxygen radical by arsenic trioxide in topoisomerase normal and mutation cell lines, and it was suggested that topoisomerase I was involving in the anticancer action of arsenic trioxide. The inverse proportion relation between the susceptibility of arsenic trioxide and the quantity of detoxification enzyme GSH was detected. It was also showed that topoisomerase I participated in generating of the DNA rudder at the time of the apotosis by the anti-neoplasm agent. Less