Studies on the Effect of 8-Azaguanine on

Since the observations of Kidder et al. (8) that 8-azaguanine selectively inhibits the development of three types of mouse neoplasms, many investi gators have examined the carcinostatic power of this compound on a variety of cancer tissues in different animal species. It has been found that 8-azaguanine is active against many additional malignant neoplasms (5, 6, 9, 10, 14, 16) but produces little or no effect on others (3, 5, 6, 9, 10, @ 15, 16). Some investigators (5, 8) have reported a @ lack of toxicity in the host at doses that inhibit @ tumor growth; others (6, 16) have not observed @ a well defined separation of the tumor inhibitory @ action of 8-azaguanine from systemic effects of the compound as manifested in reduced food in take, weight loss, leukopenia, morphological @ damage, and death. Few or insignificant histo logical changes in tumors inhibited by 8-azagua nine have been reported. Kidder ci at. (8) reported that it did not cause the death of E 0771 cells in C57 mice but only checked their growth. Sugiura and his associates (16), who also examined the effect of 8-azaguanine on E 0771 in C57 strain mice, observed small islands of active tumor tissue sur rounded by gelatinous edema and necrosis. The most striking tumor damage was reported by Gellhorn et a!. (5) and by Shapiro and his asso ciates (14), who examined the histological changes induced in the Brown-Pearce carcinoma in rabbits. They observed that the tumor cells of treated rabbits were larger and fewer in number (5, 14), contained condensations of nuclear material in irregular clumps (5), and that the mitotic index was markedly reduced (14). While Shapiro et al. (14) also demonstrated that the mitotic indices of the intestinal epithelia and of the testes of