Toxicity of Tritiated Thymidine in P388F Lymphoma Cells

Summary

The incorporation of thymidine into the newly-synthesized DNA of P388F lymphoma cells, increases non-linearly with respect to an increasing concentration of ³H-thymidine (TdR) of constant specific activity. As the external TdR concentration rises, in the presence of a constant low level of tritium a progressively greater proportion of the incorporation is hydroxyurea-resistant. These effects are attributed to negative-feedback actions of TdR metabolites on nucleotide biosynthesis.

Thymidine incorporation is stimulated at high specific activities of ³H-TdR, largely owing to enhanced hydroxyurea-sensitive DNA synthesis, resulting from DNA damage produced by the incorporated tritium. For concentrations of ³H-TdR up to 8·4 mµM, reduced survival of P388F cells is solely the result of effects of tritium incorporated into newly-synthesized DNA.