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Transient Regression of Murine Spontaneous Mammary Tumors with Analogs of Dimethyldiaminobenzene

( Laboratories of The Rockefeller Institute for Medical Research, New York, N.Y.)

1,2-Dimethyl-4-amino-5-hydroxybenzene (DMAP), an antimetabolite of 1,2-dimethyl-4,5-diaminobenzene, caused some spontaneous mammary tumors of Swiss or of C strain mice to decrease in size or to disappear. More than half of the treated animals were not thus affected by this substance. In most of the affected animals the tumor decreased in size but did not disappear. In every instance of regression, the effect was transient, and eventually the tumor grew once more and killed the host. The DMAP was not detectably toxic to adult mice. A satisfactory quantitative method for the estimation of DMAP in mouse tissues was described. Mice were found to destroy or to excrete DMAP injected into them, but 12–40 per cent of a single dose could be recovered from a mouse 5 hours after administration. Individual mice of the single Swiss strain were observed to differ with respect to the percentage of an injected dose which they destroyed. Although the proportion of mice actively destroying DMAP corresponded roughly to the proportion of tumorous mice which did not respond to this compound, the magnitude of the difference in capacity to destroy DMAP was not considered great enough to explain completely why some tumors were caused to regress and others were not. The reappearance of obliterated tumors was not associated with the acquisition of great ability to destroy DMAP. However, all mice in which tumors had been caused to regress by injection of DMAP showed less than average capacity to destroy the drug.

A barely perceptible effect in causing regression of spontaneous mammary tumors in C and in C3H mice was observed with another antimetabolite of dimethyldiaminobenzene, viz., 1,2-dichloro-4,5-diaminobenzene. A quantitative method for the estimation of this compound in mouse tissues was developed. The use of this method revealed that mice readily destroyed this substance.

One-half of a group of Swiss mice bearing spontaneous mammary tumors exhibited either a decrease in size or a complete obliteration of the tumors when the animals were injected daily with a mixture of 1,2-dimethyl-4-(p-carboxyphenylazo)-5-hydroxybenzene and 1,2-dichloro-4-(p-nitrobenzenesulfonylamido)-5-nitrobenzene. These aggregate analogs of dimethyldiaminobenzene and p-aminobenzoic acid were not able to cause permanent destruction of the tumors, because those which had been obliterated reappeared after several months.

Received 10/30/52.

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