Differential Formation of Hydroxyl Radicals by Adriamycin in Sensitive and Resistant MCF-7 Human Breast Tumor Cells: Implications for the Mechanism of Action

Birandra K. Sinha, Aspandiar G. Katki, Gerald Batist, Kenneth H. Cowan, Charles E. Myers

Research output: Contribution to journalArticle

201 Scopus citations

Abstract

Adriamycin-stimulated formation of OH in sensitive and resistant subline of human breast tumor cells (MCF-7) has been examined by electron spin resonance spectroscopy. It was shown that adriamycin significantly stimulated the formation of OH spin adducts [5,5-dimethyl-1-pyrroline N-oxide (DMPO)-OH] in the sensitive cells but not in the resistant cells. By use of spin-broadening techniques and inhibition of OH with high molecular weight poly(ethylene glycol), which does not enter intact cells, it was shown that 60-65% of adriamycin-induced OH were located extracellularly and were metal ion dependent since they were decreased in the presence of desferal. Furthermore, superoxide dismutase and catalase, enzymes that detoxify superoxide and hydrogen peroxide, also significantly inhibited adriamycin-induced OH formation and protected against the cytotoxicity of adriamycin. The differential OH formation in these two cell lines is not due to diminished activities of flavin-dependent activating enzymes nor decreased accumulation of the drug in the cells but appears to be related to enhanced activities of detoxifying enzymes, particularly, glutathione peroxidases in the resistant cells.

Original languageEnglish (US)
Pages (from-to)3776-3781
Number of pages6
JournalBiochemistry
Volume26
Issue number13
DOIs
Publication statusPublished - Jan 1 1987

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ASJC Scopus subject areas

  • Biochemistry

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