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Mutagenicity of thymidine to cultured Chinese hamster cells

Naturevolume 274pages607608 (1978) | Download Citation



THYMIDINE starvation is known to be both toxic and mutagenic to various prokaryotes, including Escherichia coli1,2, Bacillus subtilis3 and bacteriophage T4 (refs 4–6). Base excess, as well as base starvation, can also be mutagenic. For instance, Bernstein et al.5 showed that a superabundance of exogenous thymidine (4 mM) produced an increased reversion rate for some T4 amber mutants. In mammalian cells a superabundance of exogenous thymidine is toxic, perhaps by inhibiting DNA synthesis7–9. The mechanism for these effects may be related to the observations that dTTP inhibits the enzymatic reduction of CDP to dCDP by ribonucleoside diphosphate reductase10 and also that thymidine reduces the dCTP pools of Chinese hamster cells to 90% of normal11. We report here that a superabundance of exogenous thymidine is both toxic and highly mutagenic to V-79 Chinese hamster cells but that hydroxyurea, an inhibitor of ribonucleoside diphosphate reductase, is toxic but not mutagenic.

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  1. Laboratory of Molecular Pharmacology, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20014



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