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-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.
Millard
J T
JT
Department of Chemistry, Colby College, Waterville, Maine 04901.
Beachy
T M
TM
D044503:5-Methylcytosine; D001483:Base Sequence; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry; D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D004249:DNA Damage; D015226:Dinucleoside Phosphates / Q000737:chemistry; D004492:Edetic Acid / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D017665:Hydroxyl Radical; D008745:Methylation; D016685:Mitomycin / Q000737:chemistry*; D008969:Molecular Sequence Data; D009691:Nucleic Acid Denaturation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry
D044503:5-Methylcytosine; D003432:Cross-Linking Reagents; D003596:Cytosine; D004247:DNA; D015226:Dinucleoside Phosphates; D004492:Edetic Acid; D005296:Ferrous Compounds; D017665:Hydroxyl Radical; D016685:Mitomycin; D009838:Oligodeoxyribonucleotides; C055526:Fe(II)-EDTA; C015772:CpG dinucleotide