Molecular Pharmacology, Vol 3, 195-203, Copyright © 1967 by the American Society for Pharmacology and Experimental Therapeutics

Interaction of Nitrogen Mustard with Polyribonucleotides, Ribosomes, and Enzymes Involved in Protein Synthesis in a Cell-Free System

¹ Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48104

The effects of nitrogen mustard (HN2) on synthetic polyribonucleotides, ribosomes, and enzymes involved in protein synthesis in an Escherichia coli cell-free system were investigated. It was found that HN2 decreased the coding capacity of three synthetic polymers: poly A, poly U, and poly C. Poly C and poly U were more sensitive to HN2 than poly A. Ribosomes and protein synthesizing enzymes (100,000 g supernatant) obtained from E. coli cells were preincubated with drug and assayed for activity in the cell-free polypeptide synthesizing system. The effect of nitrogen mustard on the ribosomes was concentration dependent; lower concentrations (10^-6 to 10^-4 M) stimulated polypeptide synthesis while higher concentrations (10^-3 M) inhibited synthesis. Protein-synthesizing enzymes were inhibited by nitrogen mustard at both high and low concentrations. These results suggest possible sites of action of the biological alkylating agent HN2 at the level of genetic code translation of messenger RNA into protein.

Note:
ACKNOWLEDGMENTS The authors wish to thank Linda Galligher for her excellent technical assistance. Nitrogen mustard was a gift from Merck Sharp and Dohme, Rahway, New Jersey.

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