The Incorporation of Guanine into Nucleic Acids of Tumor-bearing Mice*

Since guanine is a normal constituent of nucleic acids, the possibility of the direct incorporation of this purine is of great significance in the biosynthesis of nucleic acids. Earlier reports in the literature indicated that preformed guanine was not utilized for nucleic acid production in the rat (1, Z), but more recent evidence suggested that a trace of guanine may be incorporated in the nucleic acids in various mammals. Investigations have established a small but definite incorporation of guanine in the Sherman strain rat (3), the Sprague-Dawley rat (4), and in rabbit bone marrow (5). This confirmed some earlier work with N15 in which it was shown that the C57 black mouse also utilized directly a small amount of administered guanine (6). The close structural analogy between guanine and S-azaguanine suggested the possibility that the carcinostatic action of the latter might be due to its interference in the metabolism of guanine. Previous investigations in this laboratory (7) have shown that S-azaguanine was effective in inhibiting the growth of sarcoma 37 in CAFl mice. It seemed, therefore. that this strain was especially well suited for the study of the possible incorporation of guanine. If this were the case, the extent of its introduction into the guanine component of desoxyribose nucleic acid (DNA) and pentose nucleic acid (PNA) of the internal organs and sarcoma became of interest. Furthermore, the possible conversion of guanine to adenine hitherto had received little attention and required elucidation. This experiment was also well suited to study this process. For these investigations, guanine-Cl4 was injected into sarcoma-bearing mice, the nucleic acids were extracted and degraded to the component purines, and their specific activity was measured.