PMID- 2820475
OWN - NLM
STAT- MEDLINE
DCOM- 19871116
LR  - 20220311
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 26
IP  - 13
DP  - 1987 Jun 30
TI  - Differential formation of hydroxyl radicals by adriamycin in sensitive and 
      resistant MCF-7 human breast tumor cells: implications for the mechanism of 
      action.
PG  - 3776-81
AB  - 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.
FAU - Sinha, B K
AU  - Sinha BK
AD  - Clinical Pharmacology Branch, National Cancer Institute, Bethesda, Maryland 
      20892.
FAU - Katki, A G
AU  - Katki AG
FAU - Batist, G
AU  - Batist G
FAU - Cowan, K H
AU  - Cowan KH
FAU - Myers, C E
AU  - Myers CE
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (5,5-dimethylpyrrolidin-2-one-1-oxide)
RN  - 0 (Cyclic N-Oxides)
RN  - 0 (Free Radicals)
RN  - 0 (Hydroxides)
RN  - 3352-57-6 (Hydroxyl Radical)
RN  - 80168379AG (Doxorubicin)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - J06Y7MXW4D (Deferoxamine)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Breast Neoplasms/*drug therapy/enzymology
MH  - Catalase/physiology
MH  - Cell Line
MH  - *Colony-Forming Units Assay
MH  - Cyclic N-Oxides/pharmacology
MH  - Deferoxamine/pharmacology
MH  - Doxorubicin/*pharmacology
MH  - Drug Resistance
MH  - Electron Spin Resonance Spectroscopy
MH  - Female
MH  - Free Radicals
MH  - Glutathione Peroxidase/physiology
MH  - Humans
MH  - Hydroxides/biosynthesis
MH  - Hydroxyl Radical
MH  - Oxygen/metabolism
MH  - Superoxide Dismutase/physiology
MH  - *Tumor Stem Cell Assay
EDAT- 1987/06/30 00:00
MHDA- 1987/06/30 00:01
CRDT- 1987/06/30 00:00
PHST- 1987/06/30 00:00 [pubmed]
PHST- 1987/06/30 00:01 [medline]
PHST- 1987/06/30 00:00 [entrez]
AID - 10.1021/bi00387a006 [doi]
PST - ppublish
SO  - Biochemistry. 1987 Jun 30;26(13):3776-81. doi: 10.1021/bi00387a006.