Biological activity and biochemical mechanisms of action studies of [upsilon]-ox and thymox in cultured L1210 cells

Thymox and Vox induced time and concentration dependent cytotoxic and cytostatic effects in LI210 cells. Affected cells were irreversibly blocked in the G2 phase of the cell cycle. Minimum effective exposure time of cells to Vox and thymox was 30 minutes and 2 hours respectively. In synchronized cells, both compounds were cytotoxic in all cell cycle phases, but exhibited greatest effect in late Gl-early S and in G2. Biochemical mechanisms of action included inhibition of ONA more than RNA synthesis. Activity of DNA and RNA polymerases in crude cellular extracts were reduced. Protein synthesis was inhibited, but some protein and RNA synthesis appeared to continue in G2 blocked cells. Microtubule protein levels, detected by the colchicine binding assay, were greatly reduced. Preliminary evidence suggests that Vox and thymox inhibited the synthesis of microtubule protein. This may account in part for the arrest of cells in the G2 phase of the cell cycle.