Abstract | PURPOSE: METHODS: A pBR322 plasmid DNA damage assay was used as a sensitive method for detecting strand breaks in DNA exposed to idarubicin in the presence of P450 reductase and cofactor NADPH under various incubation conditions. In addition, the rates of idarubicin reduction by P450 reductases purified from phenobarbital-treated rabbit liver, beef liver and sheep lung microsomes were determined by measuring NADPH oxidation at 340 nm. RESULTS: CONCLUSION: Our findings implicated bioreduction of idarubicin by P450 reductase and subsequent redox cycling under aerobic conditions as being one mode of idarubicin action potentially contributing to its antitumor effect.
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Authors | Haydar Celik, Emel Arinç |
Journal | Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
(J Pharm Pharm Sci)
Vol. 11
Issue 4
Pg. 68-82
( 2008)
ISSN: 1482-1826 [Electronic] Canada |
PMID | 19183515
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Reactive Oxygen Species
- Mitomycin
- NADP
- DNA
- Cytochrome P-450 Enzyme System
- NADPH-Ferrihemoprotein Reductase
- Idarubicin
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Topics |
- Animals
- Cytochrome P-450 Enzyme System
(metabolism)
- DNA
(metabolism)
- DNA Cleavage
- Humans
- Idarubicin
(metabolism, therapeutic use)
- Lung
(enzymology)
- Microsomes
(enzymology, metabolism)
- Mitomycin
(metabolism)
- NADP
(chemistry, metabolism)
- NADPH-Ferrihemoprotein Reductase
(isolation & purification, metabolism)
- Oxidation-Reduction
- Reactive Oxygen Species
(metabolism)
- Sheep
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