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Studies on the biosynthesis of nucleic acids by Novikoff hepatoma tissue in vitro Scrimgeour, Kenneth Gray

Abstract

Nucleic acid metabolism has been studied in vitro with suspensions of Novikoff rat hepatoma cells. The formation of acid soluble and nucleic acid purines from formate-C¹⁴ and adenine-8-C¹⁴ has been measured. In all cases, adenine had a higher specific activity than guanine. The acid soluble purines were much more radioactive than the nucleic acid purines. Adenine-8-C¹⁴ gave a higher value for the ratio of the specific activities of adenine to guanine nucleotides than that obtained from formate-C¹⁴. Both ribonucleic acid and deoxyribonucleic acid incorporated radioactivity in this system. A standardized set of conditions suitable for testing the activity of possible chemotherapeutic and inhibitory agents was established, and 4 such compounds were examined. Azaserine in low doses was extremely effective in inhibiting de novo purine biosynthesis. 6-Mereaptopurine also blocked de novo synthesis of the purines. A new possible antimetabolic compound; N-benzoylglycinamidine was tested. In low amounts, N-benzoylglycinamidine stimulated purine biosynthesis, but a large dose decreased both purine synthesis and respiration. The Novikoff tumour cell suspension was used to gain some knowledge of the mode of action of actinomycin D. This antibiotic inhibited cellular respiration, but not anaerobic glycolysis. Actinomycin D decreased nucleic acid biosynthesis and acid soluble guanine synthesis, but did not affect the formation of acid soluble adenine. Large amounts either of calcium pantothenate or of coenzyme A were able to reverse the inhibition of nucleic acid metabolism, and to reverse partially the inhibition of respiration. Coenzyme A was more effective than pantothenate. These findings appear to support the suggestion that actinomycin D interferes with coenzyme A-dependent reactions.

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