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.
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004277:DNA, Single-Stranded / Q000378:metabolism*; D003630:Daunorubicin / Q000494:pharmacology; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism*
D004277:DNA, Single-Stranded; D004317:Doxorubicin; D013936:Thymidine; D003630:Daunorubicin