Comparative effects of doxorubicin and 4'-epi-doxorubicin on nucleic acid metabolism and cytotoxicity in a human tumor cell line.
The effects of 4'-epi-doxorubicin (4'E-Dx) and doxorubicin (Dx) on cell survival were investigated after treatments for 1 or 24 h. It was found that after short-term exposure, 4'E-Dx causes a higher level of killing than Dx, whereas a similar cytotoxic response is detectable after 24 h. Under the same experimental conditions (treatment for 1 or 24 h) at equimolar concentrations, the two anthracyclines were equally inhibitory to DNA or RNA synthesis. Both the degree and the rate of induction of DNA strand breakage over a 1-h drug exposure were higher for 4'E-Dx than for Dx. These data were related to results of experiments carried out to investigate the rates of uptake and egress of the anthracyclines. From this study we concluded that no relationship can be established between the cytotoxicity of 4'E-Dx and Dx and their ability to inhibit DNA and RNA synthesis. In addition, the different DNA-damaging action of the two drugs does not appear to be solely dependent on the different rates of cellular uptake.
Cantoni
O
O
Istituto di Farmacologia e Farmacognosia, Universita' degli Studi di Urbino, Italy.
Sestili
P
P
Cattabeni
F
F
Geroni
C
C
Giuliani
F
F
D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage; D004317:Doxorubicin / Q000032:analysis / Q000494:pharmacology*; D015251:Epirubicin / Q000032:analysis / Q000494:pharmacology*; D006801:Humans; D009696:Nucleic Acids / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D009696:Nucleic Acids; D015251:Epirubicin; D012313:RNA; D004317:Doxorubicin; D004247:DNA