Protection of L5178Y cells by vitamin E against acute hydroxyurea toxicity does not change the efficiency of ribonucleotide reductase-mediated hydroxyurea-induced cytotoxic events.

Exposure of L5178Y cells in culture to 0.2 mM hydroxyurea (HU) for up to 48 h induces inhibition of DNA synthesis, killing of about 20% of cells during the first 24 h exposure, gradual progress of cells into the state of unbalanced growth (measured as progressive increase in cell size, DNA protein ratio and acid phosphatase activity) with final death of the majority of cells. These effects were used to compare effectiveness of rapid and late HU cytotoxicity in cells treated with HU in the presence or absence of vitamin E, employed as a protective agent against non-specific toxicity of HU. It has been found that while the presence of vitamin E prevents cell killing induced by HU treatment during first 24 h, its presence does not change the progress of cells into the state of unbalanced growth and final cell killing. It is suggested that the protection exerted by vitamin E against HU-induced side toxicity does not change the effectiveness of ribonucleotide reductase-mediated DNA synthesis inhibition, leading to cell death through the state of unbalanced growth.