STUDIES ON THE INDUCTION OF THYMINE DEFICIENCY AND ON THE EFFECTS OF THYMINE AND THYMIDINE ANALOGUES INESCHERICHIA COLI

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Abstract
E. coli strain B grown in the presence of sulfanilamide has a thymine deficiency, among others. If the requirements other than thymine are met by supplementing the medium, approximately 90% of the bacteria die in the time necessary for one division. If an amino acid or purine requirement is not met, then the bacteria do not grow and are not killed. Prevention of growth by imposing an amino acid requirement on the thymine requirement markedly reduces death in the absence of thymine. Significance of these results is discussed in relation to the use of antifolic acid agents in tumor chemotherapy, in the inhibition of plant growth, and in the induction of chromosome breaks in mitosis. A number of pyrimidines and their analogues were tested for ability to compete with thymine in the multiplication of the thymineless strain 15t. Uracil at high concentrations acts as a thymine analogue. 5-Bromouracil appears to compete with and to replace thymine in supporting growth and nucleic acid synthesis in 15t-, but cells incorporating this pyrimidine in their DNA were capable of only one division and then were killed irreversibly as incorporation of the analogue continued. The compound was relatively ineffective in the presence of thymidine. The thymidine analogues thymidine ribofuranoside, spongo-thymidine, and 5-bromouracil deoxyriboside, were inhibitors of division of 15t- in the presence or absence of thymidine. The compounds were inactive with E. coli strain B and strain Wc-. Under conditions of normal growth, the riboside was slowly degraded by 15t-. Spongothymidine was much less active than the bromouracil deoxyriboside. Significance of these results was discussed.