Selective inhibition of eukaryotic RNA polymerase: a possible new mechanism of antitumor drug action.

N-Trifluoroacetyladriamycin-14-O- Hemiadipate (AD 143), a new derivative of adriamycin with greater antitumor activity and lower cardiotoxicity, was shown not to interact with DNA and yet inhibit the activities of both RNA polymerases I and II of chicken myeloblastosis cells in vitro with ID50 values equal to 6.5 microM and 7 microM, respectively. On the other hand, an approximately 35-fold higher concentration of AD 143 was required to cause a similar inhibition of the activity of DNA polymerase alpha from chicken myeloblastosis cells. Under the same assay conditions, AD 143 had even less effect on either RNA polymerase or DNA polymerase I of E. coli cells (ID50 greater than 265 microM for both enzymes). These studies suggest that AD 143, in contrast to its parental drug adriamycin, may have a selective inhibitory effect against eukaryotic RNA polymerases.