Document Detail

The interaction of Fe(III), adriamycin and daunomycin with nucleotides and DNA and their effects on cell growth of fibroblasts (NIH-3T3).
MedLine Citation:
PMID:  8744894     Owner:  NLM     Status:  MEDLINE    
The interactions of the iron complexes of the anthracycline antitumour drugs daunomycin (DN) and adriamycin (ADM) with the mononucleotide AMP, herring sperm DNA, plasmic pBR322 and immortalized 3T3 fibroblasts were studied. By means of Mössbauer spectroscopy it was demonstrated that DNA is a powerful ferric iron chelator as compared with AMP, which is not able to compete with DN or acetohydroxamic acid for ferric iron. The difference between AMP and DNA is postulated to be based on the chelate effect. The Mössbauer spectra of the ternary Fe-anthracycline-DNA systems differ from Fe-anthracycline binary complexes, indicating rearrangement reactions. Dialysis experiments clearly disclose the formation of a ternary Fe-ADM-pBR322 complex, the topology of which differs substantially from intercalating ADM. The effect of Fe-ADM complexes (3:1) on the growth of immortalized mouse embryonal fibroblasts (NIH-3T3) was studied in comparison with ADM alone. No significant difference on the inhibition of cell growth was noticed, suggesting comparable cytotoxicity for the compounds. In contrast to literature data, no evidence was found for DNA cleavage by ferric ADM at molar ratios as high as 1/100 (ADM/base pair), even if the ternary systems were prepared in the light and in the presence of reducing or oxidizing agents. Based on our observations it seems that the cytotoxicity of both ADM and Fe-ADM oligomer is not based primarily on intercalation or direct interaction with DNA.
I Di Liegro; A Cestelli; B F Matzanke; E Bill; A X Trautwein
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine     Volume:  9     ISSN:  0966-0844     ISO Abbreviation:  Biometals     Publication Date:  1996 Apr 
Date Detail:
Created Date:  1997-03-11     Completed Date:  1997-03-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9208478     Medline TA:  Biometals     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  121-30     Citation Subset:  IM    
Dipartimento di Biologia Cellulare, Università di Palermo, Italy.
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MeSH Terms
3T3 Cells
Adenosine Monophosphate / chemistry*,  pharmacology
Biological Transport
Cell Division / drug effects*
DNA / chemistry*,  pharmacology
Daunorubicin / chemistry*,  metabolism,  toxicity
Doxorubicin / chemistry*,  metabolism,  toxicity
Iron / chemistry*,  toxicity
Plasmids / chemistry
Spectroscopy, Mossbauer
Reg. No./Substance:
20830-81-3/Daunorubicin; 23214-92-8/Doxorubicin; 61-19-8/Adenosine Monophosphate; 7439-89-6/Iron; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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