524 R. E. HANDSCHUMACHEU AND A. D. WELCH 



been shown not only to suppress the "adaptive" formation of diphospho- 

 pyridine nucleotide in rats, perhaps by forming the corresponding analog 

 nucleotide, but also to increase by fourfold the output of uric acid in 

 man. 562 ' 563 The data indicate that this is a true stimulation of purine syn- 

 thesis and that the effect could be nullified by nicotinamide. 



Finally, it would be a grave omission to neglect the multitude of factors 

 which, operating through compounds normally present in cells, control some 

 of the many biosynthetic processes involved in the formation of nucleic 

 acids. Certain examples may be mentioned, but space does not permit a 

 complete discussion of these metabolic regulators. The observation that 

 partial hepatectomy of one of a pair of parabiotically joined rats gives rise 

 to an increased mitotic index in the liver of the partner, 564 as well as to in- 

 creased uptake of phosphate-P 32 , suggests the participation of a humoral 

 factor which triggers cell division and, thus, must first initiate an increase 

 in the synthesis of nucleic acids. 565 The role of many factors affecting 

 growth, and hence nucleic acid synthesis, has been reviewed recently 566 and 

 the effects of growth hormone, testosterone, and hypothyroidism on the in- 

 corporation of uracil into the RNA of rat liver have been presented. 554 

 Similarly, a factor has been reported to be present in normal liver which sup- 

 presses the incorporation of formate into the DNA thymine of bone mar- 

 row. 567 More specific examples may be found in the "negative feed-back" 

 effects on the synthesis of orotic acid in E. coli of uracil in whole cells and 

 of cytidylic acid in cell-free preparations. 568 A similar phenomenon has been 

 reported for purine synthesis with resting-cell suspensions of this organ- 

 ism. 569 A more recent report has established the feed-back control by ade- 

 nine and guanine nucleotides of a partially purified preparation of amido 

 transferase from pigeon liver which forms ribosylamine-5-phosphate from 

 pyrophosphorylribose-5-phosphate and glutamine. 570 



It is apparent that a proper consideration of the effects of the agents dis- 

 cussed in this chapter must include an evaluation of their effects on many 

 intrinsic control mechanisms within the cell, as well as any direct effect 

 which they may exert on the enzymes involved in the synthesis of nucleic 

 acids. 



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563 J. E. Seegmiller, A. I. Grazzel, and L. Liddle, Federation Proc. 18, 321 (1959). 



564 N. L. R. Bucher, J. F. Scott, and J. C. Aub, Cancer Research 11, 457 (1951). 



565 J. L. Van Lancker and D. G. Sempoux, Arch. Biochem. Biophys. 80, 337 (1959). 



666 K. E. Paschkis, Cancer Research 18, 981 (1958). 



667 J. S. Dunning and L. Wiles, Science 129, 336 (1959). 



668 R. A. Yates and A. B. Pardee, /. Biol. Chem. 221, 757 (1956). 

 569 J. Gots, J. Biol. Chem. 228, 57 (1957). 



«° J. B. Wyngaarden and D. M. Ashton, Nature 183, 747 (1959). 



