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Molecular Pharmacology, Vol 11, 701-707, Copyright © 1975 by the American Society for Pharmacology and Experimental Therapeutics

Effect of S-Adenosylhomocysteine and S-Tubercidinylhomocysteine on Transfer Ribonucleic Acid Methylation in Phytohemagglutinin-Stimulated Lymphocytes

CHI-DEU CHANG 1 and JAMES K. COWARD 1

1 Department of Pharmocology, Yale University School of Medicine, New Haven, Connecticut 0651O

Methylation of tRNA in stimulated rat lymphocytes was studied by monitoring the incorporation of [methyl-3H]methionine into tRNA. S-Adenosylhomocysteine and the 7-deaza analogue, S-tubercidinylhomocysteine, both known to inhibit tRNA methylases in vitro, were used to block the methylation of tRNA in stimulated lymphocytes. Both these drugs affected the synthesis and methylation of tRNA when added at various times during the cell cycle. However, S-adenosylhomocysteine stimulated DNA synthesis while S-tubercidinylhomocysteine inhibited it. These opposite effects are presumably due to metabolism of the drugs to homocysteine and either adenosine or tubercidin.

Note:
ACKNOWLEDGMENT We thank Dr. Joseph R. Bertino for several helpful discussions and valuable criticism.

Submitted on December 10, 1974






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