Studies on the Metabolism of Human Tumors IV. Certain Aspects of Guanine Metabolism*t

There is a small bu t real incorporation of exogenously supplied guanine into the nucleic acid of normal rats (4). The low value of isotope found in the nucleic acids is consistent with the previously published observations with N 15, which indicated no detectable utilization (10, 19), since the amount of incorporation was less than could have been determined with the stable nitrogen isotope. I t was suggested at tha t t ime tha t guanine was not extensively incorporated into nucleic acid purines because guanase was universally present and this hydrolyt ic enzyme destroyed the guanine before it could be converted into a more immediate precursor of nucleic acids. Kidder and co-workers (14) suggested tha t tumors can utilize guanine for nucleic acid synthesis more extensively than normal tissues. This in terpreta t ion was based on the observation tha t a guanine analog, 8-azaguanine, was able to inhibit the growth of certain animal tumors. These conclusions were substant ia ted by Brown et at., who administered massive doses of N15-1abeled guanine to C57BL mice bearing adenocarcinoma E 0771 and found tha t this tumor used guanine (10). More recently guanine-C '4 has been administered to animals bearing a number of tumors, and in every instance studied guanine was a very poor precursor in the tumor compared with the host tissues, which themselves used the guanine very sparingly (5, 6, 9, 17). These observations appear to be in direct contradiction to those which were made on E 0771 in the C57BL mouse. However, examination of the experimental details reveals several differences: (a) the tumor E 0771 was not one which had been studied in the more recent work (5, 6, 9); (b) the compound was administered a t a much higher level to the C57BL mice bearing E 0771; and (c) the compound had been given over a period of 6 days in the original