Assessment of Cross-Resistance in Adriamycin- and Mitoxantrone-Resistant Cell by Flow Injection Analysis.
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The cross-resistance pattern of daunorubicin (DNR) in adriamycin (ADR)- and mitoxantrone (MTN)-resistant sublines was examined by measuring DNA strand-break and drug accumulation by flow injection analysis (FIA). Drug accumulation and retention were lower in both the resistant sublines compared with their values for sensitive ones. The cytotoxicity studies showed that ADR- and MTN-resistant cells were 15 and 12 fold cross-resistant to DNR. A significant reduction in DNR-induced DNA damage was observed in both the resistant sublines even at the same intracellular concentration, suggesting the role of altered topoisomerase II activity in resistance. A good positive correlation between cytotoxicity and strand-break results emphasizes the significance of DNA strand-break measurement to monitor development of drug resistance.
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日本酸化ストレス学会 | 論文
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