CHEMISTRY OF PURINES AND PYRIMIDINES 105 



serve as a precursor of the guanine of nucleic acids of the rat'-^' and the 

 purines of those of other species (see Chapters 23 and 25) . EarHer studies, 

 however, revealed DAP to be a potent inhibitor of L. casei; this inhibition 

 could be reversed by adenine.'-^" '"-^^ Many other effects of DAI^ have been 

 recorded (summarized in Wright-''^), and these include a prolongation of 

 the life of leukemic mice"'' '"^ and damage (which is prevented by adenine) 

 to sarcoma cells in tissue culture"^ and to the hematopoietic apparatus and 

 intestinal epithelium of small mammals.-" DAP affects a number of bio- 

 logical systems rich in nucleic acids: it inhibits the multiplication of vaccinia 

 virus in chick embryonic tissue,"^ of Russian Spring Summer Encephalitis 

 virus in vitro^''^ and in vivo,"^^^ and of kappa particles in killer Paramecium 

 aurelia}^^ '^^^ These effects are reversed by adenine. Other inhibitory ade- 

 nines are the 2-chloro,^^^ 2-thio, and 2-ethylthio derivatives.^^^ 



The ultimate replacement of the amino group of adenine by mercapto 

 has been accomplished by the treatment of hypoxanthine with phosphorus 

 pentasulfide.^'"' The resulting 6-mercaptopurine, which inhibits the growth 

 of L. casei,-^^ ■^^^'' possesses the unique and important property of rendering 

 a malignant tumor (mouse sarcoma 180) nonviable.^*^^ It has a marked 

 inhibitory effect on many mouse and rat tumors j^*^" it shows a toxicity to 

 mammals that is suggestive of an antagonism of polynucleotide biosyn- 



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(b) D. A. Clarke, F. S. Philips, S. S. Sternberg, C. C. Stock, and G. B. Elion, p. 9. 

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 p. 7. 



