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Leung, Hazel Barner (University of Pennsylvania School of Medicine, Philadelphia), Alice McGovern Doering, and Seymour S. Cohen. Effect of 9-beta-d-arabinofuranosyladenine on polymer synthesis in a polyauxotrophic strain of Escherichia coli. J. Bacteriol. 92:558-564. 1966.-Adenine-requiring mutants have been obtained from Escherichia coli strain 15 TAU, which also needs thymine, arginine, and uracil for growth. Some of these are killed by 9-beta-d-arabinofuranosyladenine (ara-A) in the absence of exogenous adenine; a particular mutant of this type, designated TAUAd, has been used in our studies. The lethality of ara-A, d-arabinosylhypoxanthine, and the 1-n-oxide of ara-A has been compared; ara-A is equally toxic in the presence or absence of thymine. Although the absence of uracil reduces ara-A toxicity, the lack of arginine almost eliminates lethality. It was found that ara-A completely inhibits deoxyribonucleic acid synthesis without markedly affecting ribonucleic acid (RNA) synthesis. Some inhibition of protein synthesis can be detected. However, the interpretation of these results is complicated because (i) exogenous adenine must be excluded, (ii) endogenous adenine is made available from RNA turnover, and (iii) ara-A is being rapidly converted to only slightly less toxic arabinosylhypoxanthine by the adenosine deaminase of E. coli. A suitable inhibitor for the bacterial deaminase has not yet been found.
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