Cytosine methylation enhances mitomycin C cross-linking

Mitomycin C (MC) is a powerful antitumor agent that targets the DNA sequence CpG. Because it is likely that this dinucleotide will contain 5-methylcytosine in vivo, we have compared the cross-linking efficiency of MC for DNA containing either 5-methylcytosine or normal cytosine embedded in random-se...

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Bibliographic Details
Published in:Biochemistry (Easton) 1993-11, Vol.32 (47), p.12850-12856
Main Authors: MILLARD, J. T, BEACHY, T. M
Format: Article
Language:English
Subjects:
5-Methylcytosine
Antineoplastic agents
Base Sequence
Biological and medical sciences
Cross-Linking Reagents - chemistry
Cytosine - analogs & derivatives
Cytosine - chemistry
Dinucleoside Phosphates - chemistry
DNA - chemistry
DNA - drug effects
DNA Damage
Edetic Acid - pharmacology
Ferrous Compounds - pharmacology
General aspects
Hydroxyl Radical
Medical sciences
Methylation
Mitomycin - chemistry
Molecular Sequence Data
Nucleic Acid Denaturation
Oligodeoxyribonucleotides - chemistry
Pharmacology. Drug treatments
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Summary:Mitomycin C (MC) is a powerful antitumor agent that targets the DNA sequence CpG. Because it is likely that this dinucleotide will contain 5-methylcytosine in vivo, we have compared the cross-linking efficiency of MC for DNA containing either 5-methylcytosine or normal cytosine embedded in random-sequence DNA oligomers. We have found that mitomycin C displays a small but significant preference for methylated DNA. Recognition of an abnormal methylation pattern in the DNA of transformed cells may therefore be one mechanism by which MC exerts its chemotherapeutic effects.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi00210a038