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Inhibition by methioninyl adenylate of focus formation by Rous sarcoma virus
Abstract:
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.
Insights
Methioninyl adenylate selectively targets Rous sarcoma virus-transformed cells by irreversibly inhibiting protein biosynthesis. This potent inhibitor halts focus formation and causes phenotypic reversion or cell death in transformed cells, unlike in normal cells.
Area of Science:
- Biochemistry
- Cell Biology
- Virology
Background:
- Methioninyl adenylate is a specific inhibitor of methionyl-tRNA synthetase, crucial for protein biosynthesis.
- Rous sarcoma virus (RSV) causes cellular transformation, leading to uncontrolled cell growth and division.
Purpose of the Study:
- To investigate the effect of methioninyl adenylate on RSV-transformed chick embryo fibroblasts.
- To determine the selective toxicity of methioninyl adenylate for transformed cells compared to normal cells.
Main Methods:
- Treatment of RSV-infected chick embryo fibroblasts with varying concentrations of methioninyl adenylate.
- Observation of focus formation, cell viability, and virus production.
- Assessment of the reversibility of protein biosynthesis inhibition in normal and transformed cells.
Main Results:
- Methioninyl adenylate (1-3 mM) irreversibly prevented focus formation in newly infected cells and eliminated existing foci.
- Transformed cells exhibited irreversible growth arrest or cell death, while normal cells showed only reversible growth arrest.
- Virus production and replication were inhibited to a lesser extent than cell transformation.
Conclusions:
- Methioninyl adenylate exhibits selective toxicity towards RSV-transformed cells.
- The differential effect is attributed to the incomplete reversibility of protein biosynthesis inhibition in transformed cells versus normal cells.
- Methioninyl adenylate shows potential as a therapeutic agent against viral oncogenesis.