TOPOISOMERASE II-ALPHA CONTENT AND TOPOISOMERASE-II CATALYTIC ACTIVITY CANNOT EXPLAIN DRUG SENSITIVITIES TO TOPOISOMERASE-II INHIBITORS IN LUNG-CANCER CELL-LINES

Purpose: Topoisomerase II alpha content, topoisomerase II catalytic ac tivity and drug sensitivities to the topoisomerase II inhibitors, doxo rubicin and etoposide, were examined in a panel of 14 unselected human lung cancer cell lines in order to determine the relationship between topoisomerase II and drug sensitivities to the topoisomerase II inhib itors. Methods: Drug sensitivities were determined using a microcultur e tetrazolium assay. The topoisomerase II alpha levels were determined by Western blot analysis and the topoisomerase II catalytic activity was determined using a decatenation assay of kinetoplast DNA, using nu clear protein from cells of each cell line. Results: Drug sensitivity tests revealed that small-cell lung cancer (SCLC) cell lines were more sensitive to drugs than non-small-cell lung cancer (NSCLC) cell lines . The relative topoisomerase II alpha levels and relative topoisomeras e II catalytic activity from SCLC cell lines (mean +/- SD 0.89 +/- 0.5 4 and 5.3 +/- 3.4, respectively) were slightly higher than those from NSCLC cell lines (0.78 +/- 0.56 and 4.0 +/- 2.8, respectively), but th e differences were not statistically significant, and not sufficient t o account for the variation in drug sensitivities. Moreover, no clear association was observed between the topoisomerase II alpha levels or the topoisomerase II catalytic activity and drug sensitivities in the cell lines studied. Conclusions: These findings suggest that the diffe rence in drug sensitivities to doxorubicin and etoposide in human lung cancer cell lines might not be explainable by the topoisomerase II al pha levels and topoisomerase II catalytic activity. Moreover, our resu lts suggest that the topoisomerase II alpha levels and topoisomerase I I catalytic activity may play a minor role in the determination of cli nical drug resistance of human lung cancers.