Effects of N-trifluoroacetyladriamycin-14-valerate and related agents on DNA strand damage and thymidine incorporation in CCRF-CEM cells.

N-Trifluoroacetyladriamycin-14-valerate (AD32) and N-trifluoroacetyladriamycin (AD41) have been compared with Adriamycin and daunorubicin in CCRF-CEM human lymphoblastic cells. All four agents produce DNA damage, as measured by alkaline unwinding methods. Thymidine incorporation, a measure of DNA synthesis, is inhibited by AD32 and AD41 and completely blocked by the other drugs. AD32 and AD41 inhibit growth of the cells after exposure for 2 hr but are considerably less potent than is either Adriamycin or daunorubicin. In drug uptake studies, cellular levels after 2-hr incubations are lower for AD32 than for Adriamycin, and both are severalfold lower than are those of daunorubicin. The results indicate that AD32 and AD41 (or their metabolites) have DNA-related effects similar to those of Adriamycin and daunorubicin. These common actions may be the proximal cytotoxic events for the four agents.