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  • Title: Influence of mitoxantrone on nucleolar function in MDA-MB-231 human breast tumor cell line.
    Author: Chegini N, Safa AR.
    Journal: Cancer Lett; 1987 Nov; 37(3):327-36. PubMed ID: 3677064.
    Abstract:
    The effect of mitoxantrone (DHAQ) on [3H]thymidine and [3H]uridine incorporation by exponentially growing MDA-MB-231, a human breast tumor cell line has been studied. The results have indicated that DHAQ was more effective in inhibiting [3H]thymidine than [3H]uridine incorporation in a concentration dependent manner. Following drug treatment at 20 ng/ml concentration, 50% inhibition of growth and [3H]thymidine incorporation were noted, whereas [3H]uridine incorporation was only inhibited by about 12%. At 2000 ng/ml of DHAQ the inhibition of cell growth, [3H]thymidine and [3H]uridine incorporations were 78%, 95% and 62%, respectively. Nuclear-associated radioactivity detected at light and electron microscope autoradiographic levels after [3H]thymidine and [3H]uridine incorporations, into DHAQ treated cells indicated that DHAQ prevented the accumulation of radioactivity into the nuclei in a concentration dependent manner. These results gave further indication that mitoxantrone induced a definitive alteration of nuclear template activities, correlated with nuclear functional-structural relation and suggested that the nucleoli were the primary site of DHAQ action.
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