PURPOSE: Topoisomerase II alpha content, topoisomerase II catalytic activity and 
drug sensitivities to the topoisomerase II inhibitors, doxorubicin 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 inhibitors.
METHODS: Drug sensitivities were determined using a microculture 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 nuclear 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 topoisomerase II 
catalytic activity from SCLC cell lines (mean +/- SD 0.89 +/- 0.54 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 the differences were not 
statistically significant, and not sufficient to 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 difference in drug sensitivities to 
doxorubicin and etoposide in human lung cancer cell lines might not be 
explainable by the topoisomerase II alpha levels and topoisomerase II catalytic 
activity. Moreover, our results suggest that the topoisomerase II alpha levels 
and topoisomerase II catalytic activity may play a minor role in the 
determination of clinical drug resistance of human lung cancers.