Reference

Effect of anthracyclines and mitoxantrone on oxygen uptake and ATP intracellular concentration in rat heart slices

Effect of anthracyclines and mitoxantrone on oxygen uptake and ATP intracellular concentration in rat heart slices. Neri, B.; Cini-Neri, G.; D'Alterio, M. (Inst. Clin. Med. Spec. Med. Pathol., Florence, Italy). Biochem. Biophys. Res. Commun., 125(3), 954-60 (English) 1984. CODEN: BBRCA9. ISSN: 0006-291X. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) In isolated rat heart cell culture mitoxantrone (I) [65271-80-9] and doxorubicin [23214-92-8] inhibited O uptake by 46 and 34%, resp., when incubated for 60 min. Epirubicin [56420-45-2], under similar conditions, inhibited cell respiration by 18% compared to untreated controls. Intracellular ATP [56-65-5] level was marked lowered by the anthracyclines and particularly by I. Thus, the cardiotoxicity of these drugs may be related to their effect on the cellular respiration and energy metab. of the heart.

Contribution of drug transport and reductases to daunorubicin resistance in human myelocytic cells

Contribution of drug transport and reductases to daunorubicin resistance in human myelocytic cells. Vasanthakumar, Geetha; Ahmed, Nahed K. (Div. Biochem. Clin. Pharmacol., St. Jude Child. Res. Hosp., Memphis, TN 38101, USA). Cancer Chemother. Pharmacol., 18(2), 105-10 (English) 1986. CODEN: CCPHDZ. ISSN: 0344-5704. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Three daunorubicin [20830-81-3] (D1)-resistant sublines (ML1/I, II, III) from the human myelocytic cell line (ML1) were generated. These sublines, ML1/I, -II, and -III, were 28-, 70-, and 162-fold, resp., more resistant than sensitive (ML1/S) cells to the cytotoxicity of D1 and were cross-resistant to adriamycin [25316-40-9], + epiadriamycin [56420-45-2], actinomycin D [50-76-0], VP-16 [33419-42-0], VM26 [29767-20-2], and mitoxantrone [65271-80-9]. Steady-state levels of D1 in resistant sublines I and II, in the presence or absence of N3, were not significantly different from those of sensitive cells. However, the steady-state level of D1 in subline III was increased in the presence of NaN3. D1 efflux was minimal in ML1/S and resistant cells in the absence of glucose [50-99-7]. Addn. of glucose enhanced D1 efflux only in subline III. Verapamil [52-53-9] increased the cellular levels of D1 and inhibited its efflux from resistant III cells but not from ML1/S cells. Verapamil also greatly enhanced the cytotoxicity of D1 for sublines I, II, and III. The differences between sensitive and resistant cells in D1 uptake and retention seemed inadequate to cause 162-fold resistance and suggested other factors may be contributing to the development of resistance. In support of this hypothesis, daunorubicin reductase [9040-58-8] activity was significantly lower in resistant cells than in ML1/S cells. The greatest decrease in activity occurred at pH 8.5, which represents aldehyde reductase [9028-12-0].