methioninyl-adenylate and Cell-Transformation--Neoplastic

Methioninyl adenylate is a specific and potent inhibitor of the enzyme methionyl-tRNA synthetase and, consequently, of protein biosynthesis. In cultures of chick embryo fibroblasts infected with Rous sarcoma virus, incubation for a 2-day period with 1 to 3 mM concentrations of this inhibitor, as late as 4 days after infection, irreversibly prevented subsequent formation of foci of transformed cells. Later addition could also elicit the irreversible disappearance of already existing foci, by phenotypic reversion and/or cell killing. Virus production in transformed cells and replication in newly infected cells were also inhibited but to a lesser degree. Under the same conditions, the same concentrations of methioninyl adenylate caused only a reversible growth arrest of normal cells. The selective toxicity of the inhibitor for transformed cells is not due to a greater affinity for the target enzyme, but it may be due to the fact that inhibition of protein biosynthesis is only partially reversible in these cells, whereas it is fully reversible in normal cells.

Topics: Adenosine Monophosphate; Amino Acyl-tRNA Synthetases; Avian Sarcoma Viruses; Cell Division; Cell Transformation, Neoplastic; Cells, Cultured; Contact Inhibition; Dose-Response Relationship, Drug; Methionine; Methionine-tRNA Ligase; Neoplasm Proteins; Virus Replication