Molecular Pharmacology, Vol 16, 278-286, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

Effects of the Plant Amino Acid Mimosine on Cell Division, DNA, RNA and Protein Syntheses in Paramecium

¹ CSIRO Division of Animal Production, Genetics Research Laboratories, P.O. box 184, North Ryde N.S.W. 2113 Australia
² CSIRO Division of Animal Production, Ian Clunies Ross Research Laboratories, P.O. box 239, Blacktown N.S.W. 2148 Australia

The amino acid mimosine completely inhibited cell division in Paramecium tetraurelia at submillimolar concentrations; DNA, RNA and protein syntheses were all found to be inhibited by mimosine. Mimosine's effect on cell division was reversible after 48 hours exposure but irreversible after 96 hours of exposure. Thymidine-5'-triphosphate was unable to protect Paramecium against the effects of mimosine. Binding of mimosine to purified DNA could not be demonstrated using either equilibrium dialysis or linear dichroic spectral ratios; the presence of 0.025 mM mimosine, however, caused temperature dependent abosrbance profiles of DNA to show a 3% hyperchromicity at 40° (1 x SSC, 250 nm) and an 8% hypochromicity after melting (above 80°). Adding mimosine to an in vitro DNA polymerase system resulted in a 30% to 50% reduction of nucleotide incorporation. DNA, mimosine and DNA polymerase may form a ternary complex that blocks both DNA and RNA syntheses; however, failure of TTP to reverse mimosine inhibition suggests that unknown factors may be involved.

Note:
ACKNOWLEDGMENTS We are greatly indebted to Dr. Jane Prosser for undertaking the RNA polymerase studies and Dr. Bengt Nordén for making the linear dichroic measurements. Dr. Merilyn Sleigh instructed us in the methods required for examining DNA breakage in E. coli and Dr. G. W. Grigg kindly supplied us with phleomycin and strains of bacteria. Finally, we are very grateful for the able and dedicated technical assistance of MrS. Lorna McKinnon and the analysis of the tritiated mimosine by Dr. J. H. O’Keefe.