Molecular Pharmacology, Vol 8, 551-560, Copyright © 1972 by the American Society for Pharmacology and Experimental Therapeutics

Effects of Deoxyribonucleic Acid-Reactive Drugs on Ribonucleic Acid Synthesis in Leukemia L1210 Cells

¹ Laboratory of Molecular Pharmacology, Office of the Associate Scientific Director for Experimental Therapeutics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20014

Drugs having various modes of interaction with DNA were examined for their effects on RNA synthesis in L1210 cell cultures. Two aspects of RNA synthesis were emphasized: effects on chain lengths of RNA molecules synthesized in the presence of drug, and selective inhibition of nucleolar 45 S RNA synthesis. The drugs studied appeared to fall into three groups. Group I (actinomycin, daunomycin, and cordycepin) caused moderate reduction in chain length of nucleoplasmic RNA and marked selectivity in inhibition of nucleolar 45 S RNA synthesis. Group II (anthramycin, nitrogen mustard, and camptothecin) caused marked reduction in RNA chain length in both nucleoplasm and nucleolus, and did not selectively inhibit nucleolar 45 S RNA synthesis. Camptothecin, however, differed from the first two in that RNA chains eventually approached normal lengths if sufficient time was allowed. Group III (proflavin, ethidium, and ellipticine) did not produce RNA chain shortening and had moderate selectivity in inhibition of nucleolar 45 S RNA synthesis. Some of these findings could be interpreted in terms of known modes of interaction with DNA. In particular, it is proposed that the degree of reversibility of the DNA-inhibitor complex is an important, although not exclusive, determinant of the type of RNA synthesis effects produced.

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ACKNOWLEDGMENTS We would like to thank Irene Clark and Rita Gertzog for their excellent technical assistance in these studies, and Mary Tyler for her help in the preparation of the manuscript.