378 GEORGE BOSWORTH BROWN AND PAUT M. ROLL 



an increase in the PNA, DNA, and protein-N content of the liver^''^ (see 

 also Chapter 16). 



c. Other Vitamins 



Biotin deficiency in rats results in a decreased incorporation of NaHC'^Os 

 into visceral nucleic acid adenine and guanine as well as into arginine, as- 

 partic acid, and citric acid.^*° It has been reported that there is a decrease 

 in the DNA content of spleen of pyridoxine-deficient animals.'*^ In rabbits 

 deficient in vitamin E there is an increased content, over that found in 

 normal animals, of PNA and DNA in skeletal muscle and of DNA in liver. ^^^ 

 It is impossible to conclude on the basis of this evidence, however, that the 

 vitamins biotin, Be , or E are directly implicated in the synthesis of nucleic 

 acids. The rate of PNA synthesis as measured by P^^ incorporation was not 

 affected by vitamin C-deficiency in monkeys,"" although it has been 

 claimed^" that ascorbic acid is involved in DNA formation in slices of 

 guinea pig tissues or rat sarcoma. 



d. Other Drugs 



In a study of the effect of nitrogen mustard (bis (i8-chloroethyl)methyl- 

 amine hydrochloride) on developing salamander embryos, it was found 

 that the drug causes a cessation of DNA synthesis but allows PNA syn- 

 thesis to continue normally. ^^^ The incorporation of formate-C" into the 

 nucleic acids of mouse viscera is inhibited by treatment of the animal with 

 2,6-diaminopurine, 8-azaguanine, cortisone, potassium arsenite, urethan, 

 and nitrogen mustard. ^^^ In the case of the nitrogen mustard, urethan, and 

 2,6-diaminopurine, this inhibition cannot be due to a general decline in 

 cellular activity since these compounds cause an increase in the overall 

 incorporation of formate and NaHC^Os into the organs of the viscera. 

 Nitrogen mustard specifically decreased the incorporation of both formate 

 and adenine into fiver DNA purines (with httle effect on that into PNA).^*^ 

 It is not known whether nitrogen mustard has any specific effect on DNA 

 synthesis or w^hether it inhibits mitosis in some unknown manner. 



'" M. R. Sahasrabudhe and M. V. Lakshminarayan Rao, Nature 168, 605 (1951). 



1^" P. R. MacLeod and H. A. Lardy, J. Biol. Chem. 179, 733 (1949). 



1" L. R. Cerecedo, M. E. Lombardo, D. V. N. Reddy, and J. J. Travers, Proc. Soc. 



Exptl. Biol. Med. 80, 648 (1952). 

 1" J. M. Young and J. S. Dinning, J. Biol. Chem. 193, 743 (1951). 

 1^3 B. I. Gol'dshtein, L. G. Kondrat'eva, and V. V. Gerasimova, Biokhimiya 17, 354 



(1952); cf. Chem. Absir. 47, 718 (1953). 

 1" D. Bodenstein and A. A. Kondritzer, J. Exptl. Zool. 107, 109 (1948). 

 1^5 H. E. Skipper, J. H. Mitchell, Jr., L. L. Bennett, Jr., M. A. Newton, L. Simpson, 



and M. Eidson, Cancer Research 11, 145 (1951). 

 1^6 D. A. Goldthwait, Proc. Soc. Exptl. Biol. Med. 80, 503 (1952). 



