Discussion

We introduce methodology to simultaneously measure: i) relative rates of replication, transcription, DNA/RNA cytosine methylation and oxidation; and ii) global levels of modified bases within a cellular context. Our approach involves feeding cells or animals stable-isotope labeled cytidine followed by isolation and analysis of nucleic acids by liquid chromatography - tandem mass spectrometry. This overall methodology will have wide application in the field of drug discovery, especially for cell based screening assays, mechanism of action studies or flexible and accurate measurements of proliferation and transcription.