Transient regression of murine spontaneous mammary tumors with analogs of dimethyldiaminobenzene.

The rationale of the following work has been given in preceding papers (3, 4, 6). According to the views there proposed, it could be expected that antimetabolites of l,2-dimethyl-4,5-diaminobenzene would be harmful to spontaneous mammary tumors of mice but not toxic to the animal as a whole. Provided that such an antimetabolite was not rapidly destroyed or excreted by the animal, the discovery of a selectively acting, tumordestroying agent should be possible. The purpose of the present paper is to describe how some of the previously known antimetabolites of dimethyldiaminobenzene affect these spontaneous, malignant growths in mice. The transposition of results found with bacteria to the problem posed in animals merits consider ation. The known antimetabolites of dimethyldiaminobenzene have been observed to act on micro organisms (6). These antimetabolites have been separated from mere structural analogs of the metabolite (which are biologically inactive) on the basis of a test with Staphylococcus aureus. It is en tirely possible that some which were inactive for this organism might be capable of functioning as antimetabolites in mammalian tissues. Similarly, animals might well be able to destroy or to excrete a potentially active compound, and thus to render it inoperative. Furthermore, the problem of get ting an antimetabolite to the desired site of action in an animal and that of keeping it there are mag nified in comparison to the related situation in microorganisms. Thus, one might anticipate that studies with bacteria would not lead without equivocation to the precise compound that would function as desired in animals. The best that could be expected is to be led to the general region of desirable effects.