Related Experiment Video
Updated: Jul 28, 2026

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
Published on: May 14, 2016
The anticancer agent ellipticine on activation by cytochrome P450 forms covalent DNA adducts
M Stiborová1, C A Bieler, M Wiessler
1Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, 128 40 2, The, Prague, Czech Republic. stiborov@prfdec.natur.cuni.cz
Abstract:
Ellipticine is a potent antitumor agent whose mechanism of action is considered to be based mainly on DNA intercalation and/or inhibition of topoisomerase II. Using [3H]-labeled ellipticine, we observed substantial microsome (cytochrome P450)-dependent binding of ellipticine to DNA. In rat, rabbit, minipig, and human microsomes, in reconstituted systems with isolated cytochromes P450 and in Supersomes containing recombinantly expressed human cytochromes P450, we could show that ellipticine forms a covalent DNA adduct detected by [32P]-postlabeling. The most potent human enzyme is CYP3A4, followed by CYP1A1, CYP1A2, CYP1B1, and CYP2C9. Another minor adduct is formed independent of enzymatic activation. The [32P]-postlabeling analysis of DNA modified by activated ellipticine confirms the covalent binding to DNA as an important type of DNA modification. The DNA adduct formation we describe is a novel mechanism for the ellipticine action and might in part explain its tumor specificity.
Related Concept Videos
Nucleotide Excision Repair
DNA Damage can Stall the Cell Cycle
Treatment Resistant Cancers
Mutations
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Nucleotide Excision Repair
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
DNA Damage Can Stall the Cell Cycle

