BIOSYNTHESIS OF NUCLEIC ACIDS 375 



garding the intermediates on the pathways leading to the immediate poly- 

 nucleotide precursors. Most studies have involved liver tissue which has a 

 high degree of polyploidy (Chapter 19). The character of the "extra" DNA 

 in those cells of unusually high DNA content and of the processes which lead 

 to that doubling of the DNA may bear on these questions, but is a subject 

 which has not been investigated. It is of interest that the incorporation of 

 formate into kidney, a tissue showing minimal polyploidy, shows^' the 

 highest PNA:DNA ratio of any organ, and the greatest apparent retention 

 of the isotope once incorporated into the DNA (Tables II and VI). The de- 

 tails of the picture of the correlation of DNA synthesis with mitosis are 

 obscured in the intestine because of the continuous production of, and 

 physical loss of, cells; in the lymphoid tissues for similar reasons; and in 

 the testes because of the slow process of reductive division. 



IV. Factors Influencing Polynucleotide Biosynthesis 



The proper functioning of any biological system requires that cellular 

 processes be subject to many controls. Although the processes of nucleic 

 acid biosynthesis are undoubtedly affected by conditions such as the nu- 

 tritional state of the animals, hormone concentrations, and certain physio- 

 logical stresses, only a few compounds are known which have any apparent 

 direct function in the biosynthesis of nucleic acids and even in these cases 

 the mechanisms of the involvement of the agents in the synthetic processes 

 are not known. Many situations have been described in which the adminis- 

 tration of a compound and the induction of a certain physiological state in 

 an animal, is followed by alterations in the amount or in the renewal of 

 tissue nucleic acids. While such conditions can truthfully be described as 

 affecting nucleic acid synthesis, it does not follow that they are directly im- 

 plicated in biosynthetic schemes. For example, agents which cause hyper- 

 plasia will also give rise to an increased rate of nucleic acid synthesis. Yet 

 such agents are not necessarily directly involved in the biosynthesis of 

 nucleic acids but may act only as general stimulants of cellular division. In 

 most cases it is impossible to determine whether the increased nucleic acid 

 production is a cause or an effect of increased mitotic activity. Thus it has 

 been reported^^^ that the administration of progesterone to castrated rabbits 

 results in an increased synthesis of the nucleic acids of the endometrium. 

 However, as this compound is known to cause extensive proliferation of the 

 endometrium, it is impossible to attribute to the hormone a direct influence 

 on nucleic acid synthesis. 



Similarly, the induction of cellular hypertrophy is often associated with 

 increased PNA content of the cell. An agent which produces hypertrophy 

 might be considered as a stimulant of PNA synthesis, yet in most cases it 

 would be difficult to establish a direct cause-and-effect relationship between 



i3« U. Borell, Acta Endocrinol. 9, 141 (1952). 



