LEVELS OF MESSENGER-RNA CODING FOR DNA TOPOISOMERASE-II ISOFORMS DO NOT CORRELATE WITH IN-VITRO DRUG-SENSITIVITY

The relationship between cellular levels of mRNA coding for DNA topois omerase II, both the alpha and beta isoforms, and in vitro sensitivity to anticancer drugs were evaluated. Using a sensitive RNA-polymerase chain reaction technique, the levels of mRNA coding for the alpha and beta isoforms of topoisomerase II were estimated relative to beta-acti n mRNA. A relatively narrow range of expression was observed across a broad range of approximately 60 human tumor cell lines representing ei ght major histological types which have been characterized in detail w ith respect to their in vitro sensitivity to standard anticancer drugs . No significant correlations were observed between mRNA level and cel lular response to drugs thought to inhibit topoisomerase II or any of the other drugs studied. These results suggest that predictive tests f or response to topoisomerase II-related drugs can not be based on esti mation of levels of mRNA.