PT  - JOURNAL ARTICLE
AU  - ŚLASKA, KRYSTYNA
AU  - SZMIGIERO, LESZEK
AU  - JAROS-KAMIŃSKA, BARBARA
AU  - CIESIELSKA, EWA
AU  - GNIAZDOWSKI, MAREK
TI  - The Mechanism of Inhibition of DNA Transcription <em>In Vitro</em> by Nitracrine (Ledakrin, C-283)
DP  - 1979 Jul 01
TA  - Molecular Pharmacology
PG  - 287--296
VI  - 16
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/16/1/287.short
4100  - http://molpharm.aspetjournals.org/content/16/1/287.full
SO  - Mol Pharmacol1979 Jul 01; 16
AB  - In the presence of mercaptoethanol or dithiothreitol, an anticancer drug nitracrine (1-nitro-9,3-N,N-dimethylaminopropylaminoacridine, Ledakrin, C-283) forms irreversible complexes of decreased template activity with DNA. Up to 7 irreversibly bound [3H]-nitracrine molecules were found per 104 nucleotides of calf thymus DNA in the presence of mercaptoethanol. Both average chain length and the number of polynucleotides decreased in the presence of the drug. It can be concluded that binding of the drug to DNA inhibits the initiation and elongation steps or induces a pre-early termination of RNA synthesis. On the other hand DNA bearing as much as 20 molecules of the drug per 103 of nucleotides (the complex formed in the presence of dithiothreitol) retains its ability to bind E. coli RNA polymerase. ACKNOWLEDGMENTS The authors are grateful to Miss Małgorzata Affeltowicz, Mrs Grażyna Obara and Mrs Krystyna Myszkowska for valuable technical assistance. We wish to thank Dr R. S. Hayward for his critical reading of the manuscript and helpful comments.