Expression of DNA Topoisomerase II alpha and clinical significance in colon cancer.

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(Basic study)DNA Topoisomerase II alpha, which catalyzes conformational changes of DNA, is closely involed in processes such as DNA replication, transcription, chromosomal condensation with the formation of transient double strand breaks during DNA TopoisomeraseII reaction. It has recentry been proposed that there is the role of TopoisomeraseII alpha in DNA repair. We analyze TopoII alpha activity during DNA repair phase caused by UV irradiation and antitumor drugs in human colon cancer cell(COLO32ODM) line useing an immunohistochemical approach. In studies on antitumor drugs, we compared TopoII alpha activity in the presence of VP-16 as inhibitors of DNA TopoisomeraseII with CDDP as giving other lesion in DNA.And we observed that it's activity is sighficantly increased in Colo32ODM administered CDDP alone but degrease in the presence of VP-16 and cmbination with CDDP.Serum depieted Colo32ODM colon cancer cell were irradiated with [UV light. Cytospin specimen of these cell were immunoc … More ytochemically stained Topo II alpha, Ki-67, apoptosis( TUNEL method). In order to observed DNA damage and synthesis, thymine dymer and BrdU were mesured simultaneously. After UV irradiation, Topo alpha expression was incresed gradually. These alterration was parallel to thinin dymer but not to Ki-67. These result suggested that Topoisomerase II alpha is involved in DNA repair not in proliferation during repair phase. Immunohistochemical staining of TopoisomeraseII alpha is a maker of cellular activity and site of DNA repair possibility a useful marker of cellular progression to other cell cycle antigen.(Clinical study)DNA topoisomerase II alpha (Topo II alpha) and Ki- 67 antigens in colon cancers from 51 pa-tients were investigated by an immunohi-stochemuical technique using monoclonal anti-Topo II alpha (8D2) and MIB-1 antibodies respectively. Positive cells of TopoII alpha and Ki-67 antigens were observed at progressive sites of all samples.Positive rates of their expressions were calculated as the number of positive cells/lOOOover cancer cells in the section.A posi-tive correlation was detected between Topo II alpha indices and Ki-67 indices (r=O.55).Although there was a relative tendency in Topo II alpha and histological grading, the-re was no significant difference and further examination is necessary for evaluation. It was suggested that Topo II alpha maybe useful as a proliferative marker for detecting colon cancer. Less