Utilization of Guanine by the C57 Black Mouse Bearing Adenocarcinoma Eo771. ∗

Abstract

The effectiveness of the triazole analogue of guanine, azaguanine, in inhibiting the growth of subcutaneous transplants of mammary adenocarcinoma Eo771 1 in mice of the C57 black strain has been reported by Kidder, Dewey, Parks and Woodside 2 and confirmed for this tumor. 3 It was suggested by Kidder and co-workers 2 that their results indicated that the tumor tissue utilizes guanine for nucleic acid synthesis while normal tissue does not.

We have investigated the incorporation of isotopically labeled guanine (containing N¹⁵ in the 1 and 3 nitrogens and in the 2-amino group 4 ) into the nucleic acids of this strain of mouse bearing this tumor. The guanine was administered in five intraperitoneal injections, of 2.4 mg each, over a 6 day period, beginning on the 7th day after implantation of the tumor. Inasmuch as isotopic nitrogen, particularly from the 2-amino group, can be contributed to body pool ammonia 4 it is not unlikely that the isotope found in the protein residue, pyrimidines and even the adenine (Table I) arose from this source. There was, however, a small but definite incorporation into the guanine of the nucleic acids, but there is no evidence of a specific uptake by the tumor since the incorporation into the guanine of the tumor tissue and into that of the non-tumorous viscera of the same mice was significant in each case.

When guanine was adminisered to an unspecified strain of the white rat 5 or to Sherman strain rats (Rockland Farms), either orally 4 or intraperitoneally, 6 there was no significant incorporation of the guanine into the tissue nucleic acids. The species difference in the purine metabolism of the Sherman rat and the C57 black mouse (bearing adenocarcinoma Eo771) makes it necessary to be conscious of other such possibilities in mammalian purine metabolism.