Characterization of covalent Adriamycin-DNA adducts
- 29 September 1998
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 95 (20), 11561-11565
- https://doi.org/10.1073/pnas.95.20.11561
Abstract
Adriamycin is a popular antineoplastic agent whose ability to form covalent adducts with DNA has been correlated to cellular apoptosis (programmed cell death) in tumor models. We have isolated and purified this adduct formed under oxido-reductive (Fenton) conditions in Tris buffer. We show by homo- and heteronuclear NMR spectroscopy that the covalent Adriamycin-DNA adduct is structurally equivalent to that resulting from direct reaction with formaldehyde. Covalent linkage of the drug to one of the DNA strands confers remarkable stability to the duplex, indicated by a 162-fold reduction in the rate of strand displacement compared with the complex with noncovalently bound drug. Glyceraldehyde also engenders covalent Adriamycin-DNA complexes, providing a possible relevant biological context for in vivo adduct formation.Keywords
This publication has 19 references indexed in Scilit:
- Production of Formaldehyde and DNA−Adriamycin or DNA−Daunomycin Adducts, Initiated through Redox Chemistry of Dithiothreitol/Iron, Xanthine Oxidase/NADH/Iron, or Glutathione/IronChemical Research in Toxicology, 1997
- Redox Pathway Leading to the Alkylation of DNA by the Anthracycline, Antitumor Drugs Adriamycin and DaunomycinJournal of Medicinal Chemistry, 1997
- Alkylation of DNA by the Anthracycline, Antitumor Drugs Adriamycin and DaunomycinJournal of Medicinal Chemistry, 1996
- Base Specific and Regioselective Chemical Cross-Linking of Daunorubicin to DNAJournal of the American Chemical Society, 1996
- Interstrand DNA crosslinking induced by anthracyclines in tumour cellsBiochemical Pharmacology, 1994
- Does Adriamycin Induce Interstrand Cross-Links in DNA?Biochemistry, 1994
- Interactions of Hydroxyl Radicals with Tris (Hydroxymethyl) Aminomethane and Good's Buffers Containing Hydroxymethyl or Hydroxyethyl Residues Produce FormaldehydeFree Radical Research Communications, 1993
- Formaldehyde crosslinks daunorubicin and DNA efficiently: HPLC and x-ray diffraction studiesBiochemistry, 1991
- Induction of stable transcriptional blockage sites by Adriamycin: GpC specificity of apparent Adriamycin-DNA adducts and dependence on iron(III) ionsBiochemistry, 1990
- DNA sequence‐specific adducts of adriamycin and mitomycin CFEBS Letters, 1989