CpG methylation potentiates pixantrone and doxorubicin-induced DNA damage and is a marker of drug sensitivity.

ABSTRACT: DNA methylation is an epigenetic modification of the mammalian genome that occurs predominantly at cytosine residues of the CpG dinucleotide. Following formaldehyde activation, pixantrone alkylates DNA and particularly favours the CpG motif. Aberrations in CpG methylation patterns are a feature of most cancer types, a characteristic that may determine their susceptibility to specific drug treatments. Given their common target, DNA methylation may modulate the DNA damage induced by formaldehyde-activated pixantrone. In vitro transcription, mass spectrometry and oligonucleotide band shift assays were utilized to establish that pixantrone-DNA adduct formation was consistently enhanced 2-5-fold at discrete methylated CpG doublets. The methylation-mediated enhancement was exquisitely sensitive

SUBMITTER: Evison BJ 

PROVIDER: S-EPMC2770666 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature