Mutagenicity of thymidine to cultured Chinese hamster cells

Abstract

THYMIDINE starvation is known to be both toxic and mutagenic to various prokaryotes, including Escherichia coli^1,2, 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 synthesis^7–9. 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.