Thymidine metabolic relationships

Hollibaugh, J. T. 1994. Relationship between thymidine metabolism bacterioplankton community metabolic capabilities and sources of organic matter used for growth. Microbial Ecology 28 117-131. 

Clive D. 1977. A linear relationship between tumorigenic potency in vivo and mutagenic potency at the heterozygous thymidine kinase (TK+/-) locus of L5178Y mouse lymphoma cell coupled with mammalian metabolism. Dev Toxicol Environ Sci 2 241-247. 

A sensitive method to measure toxic effects of drugs is to monitor cellular metabolism by incorporation of 3H-thymidine or 14C-protein hydrolysate. 14C-protein is used in preference to 3H-thymidine when it is necessary to avoid competition in uptake between the labeled thymidine and an unlabeled nucleoside reverse-transcriptase inhibitor. These methods are used mainly to monitor sublethal toxicity after initial screening or when comparing structure-activity relationships. The assays described here are carried out using 6-mL culture tubes (Note 1). These assays are carried out in parallel with the antiviral assay. 

There appears to be a relationship between the antiviral activity and the electron-withdrawing capacity of the substituents in the S-position of the nucleoside analogues as evidenced by the decrease in the antiviral activity when the methyl moiety was replaced (CF3, F > I > Br > CH3). These differences may be related to their substrate activity for thymidine kinase, which is required for activation, or to the differences in metabolic conversion to the di- or triphosphate, or to the relative afflnity of the nucleoside triphosphate analogue for the reverse transcriptase. 

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