Comparative study of demethoxydaunorubicin with other anthracyclines on generation of oxygen radicals and clonogenic survival of fibroblasts.
Demethoxydaunorubicin was compared to other anthracyclines (daunorubicin, doxorubicin, epirubicin) on its ability to generate free oxygen radicals when mixed with Fe2+ in solution and on its ability to reduce clonogenic survival of fibroblasts in culture. Oxygen electrode measurements of free radical generation showed that most of the consumed oxygen entered the monovalet oxygen reduction pathway. Catalase and superoxide dismutase additions inhibited oxygen consumption for all tested anthracyclines and diethylenetriaminepentacetic acid (DTPA) was also inhibitory except for demethoxydaunorubicin. Demethoxydaunorubicin and epirubicin dose-dependently reduced the clonogenic survival of fibroblasts. Addition of catalase or superoxide dismutase was without effect, whereas metal chelators DPTA, desferrioxamine and EDTA all protected against epirubicin-induced toxicity. Of the chelators, only desferrioxamine protected against demethoxydaunorubicin toxicity. Tests in vivo will further elucidate whether demethoxydaunorubicin also differs from the other anthracyclines in therapeutic effect as well as in side effects such as myocardial toxicity.
Department of Clinical Chemistry, Umeå University Hospital, Sweden.
K
K
Grankvist
U
U
Stendahl
R
R
Henriksson
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002614:Chelating Agents / Q000494:pharmacology; D002999:Clone Cells; D006224:Cricetinae; D003630:Daunorubicin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004566:Electrodes; D015251:Epirubicin / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005609:Free Radicals; D015255:Idarubicin / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D002614:Chelating Agents; D005609:Free Radicals; D015251:Epirubicin; D004317:Doxorubicin; D002374:Catalase; D013482:Superoxide Dismutase; D010100:Oxygen; D015255:Idarubicin; D003630:Daunorubicin