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Anthracycline Antibiotic Augmentation of Microsomal Electron Transport and Free Radical Formation
Abstract
Adriamycin, daunorubicin, and other anthracycline antibiotics dramatically augment electron flow from NADPH to molecular oxygen in rat liver microsomes and heart sarcosomes. This process is enzymatic, is dependent on NADPH (Km = 420 µM), has a pH optimum of 8.0-8.5, and is inducible by phenobarbital. The Km values for the anthracycline antibiotics range from 100 to 400 µM. Although SKF 525-A and carbon monoxide do not inhibit the anthracycline stimulation, α-tocopherol and p-hydroxymercuriphenylsulfonic acid inhibit both anthracycline-augmented and endogenous oxygen consumption. Electron spin resonance studies show that the anthraquinone nucleus of the anthracycline is reversibly converted to a free radical semiquinone, which serves to shuttle electrons to oxygen. This enhanced free radical formation may function as the toxic and/or active principle of anthracycline chemotherapy.
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Citations
Cited by
Teicher, B. A. (1994) · Cancer and Metastasis Reviews · doi:10.1007/bf00689633 · Cited by 563
Štěrba, M., Popelová, O., Vávrová, A., Jirkovský, E., Kovaříková, P., Geršl, V., & Šimůnek, T. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4795 · Cited by 329
Kalyanaraman, B., Perez-Reyes, E., & Mason, R. P. (1980) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(80)90142-7 · Cited by 317
Ito, H., Miller, S. C., Billingham, M. E., Akimoto, H., Torti, S. V., Wade, R., Gahlmann, R., Lyons, G., Kedes, L., & Torti, F. M. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.11.4275 · Cited by 255
Plosker, G. L., & Faulds, D. (1993) · Drugs · doi:10.2165/00003495-199345050-00011 · Cited by 223
Metadata
- Authors
- BACHUR, N. R., GORDON, S. L., & GEE, M. V.
- Venue
- Molecular Pharmacology
- Publisher
- Elsevier BV
- Published
- 1977-09
- Volume
- 13
- Issue
- 5
- Pages
- 901-910
- ISSN
- 0026-895X (ISSN-L)
- OpenAlex
- W2473122656
- Cited by
- 373
- References
- 0
- FWCI
- 11.23
- Type
- journal article
- Language
- en
- Open access
- closed
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- BACHUR, N. R., GORDON, S. L., & GEE, M. V. (1977). Anthracycline Antibiotic Augmentation of Microsomal Electron Transport and Free Radical Formation. Molecular Pharmacology. https://doi.org/10.1016/s0026-895x(25)12453-x
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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