PT  - JOURNAL ARTICLE
AU  - RUDDON, R. W.
AU  - JOHNSON, J. M.
TI  - The Effects of Nitrogen Mustard on DNA Template Activity in Purified DNA and RNA Polymerase Systems
DP  - 1968 May 01
TA  - Molecular Pharmacology
PG  - 258--273
VI  - 4
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/4/3/258.short
4100  - http://molpharm.aspetjournals.org/content/4/3/258.full
SO  - Mol Pharmacol1968 May 01; 4
AB  - The effects of nitrogen mustard (HN2) on DNA and RNA synthesis in preparations utilizing purified DNA templates and polymerase enzymes have been investigated in order to more completely define the mechanism of action of antineoplastic alkylating agents at the molecular level. Pretreatment of native calf thymus DNA with 5 x 10-7 M HN2 produced a significant inhibition of DNA template activity in a purified RNA polymerase system from Escherichia coli. Concentrations of HN2 20-100 times higher were required to achieve an equivalent amount of inhibition of DNA template function utilizing a DNA polymerase system from E. coli. The template activities of both native and denatured DNA were inhibited by HN2. The quantity of alkylation of the DNA templates was determined by measuring the binding of 14C-HN2, and the percent inhibition of DNA template activity was correlated with the number of alkylations per 104 nucleotide units. It was found that the template function of DNA as it exists in a nucleoprotein complex isolated from E. coli is relatively insensitive to treatment with HN2. The possible relationships of these findings to the cytotoxic effects of HN2 are discussed. ACKNOWLEDGMENT The authors wish to thank Linda Galligher for her excellent technical assistance.