Inhibition of Experimental Tumors by Orthophenylenediamine (OPDA)

Abstract

The presence in animals of certain tumors has been observed to provide either biochemical protection or liability in terms of survival time for the host when challenged with a lethal dose of specific chemical agents such as the phenylenediamines. The Cloudman S91 mouse melanoma protects its host against the acute toxicity of paraphenylenediamine (PPDA) whereas the same tumor is a disadvantage to the host when the challenging compound is orthophenylenediamine (OPDA). With the above experimental design this phenomenon was found to extend to other combinations of tumor and compound variously to the advantage, disadvantage, or neither of the host. In possible correlation, it was also observed that PPDA combines with certain pigmented tumor constituents in vitro as determined by O2-consuming reactions in the Warburg apparatus when added to melanoma tissue, urine, blood plasma, or pure dihydroxyphenylalanine (DOPA). Further pursuit of these phenomena led to the chemotherapeutic testing of the phenylenediamines against melanoma and other tumors. The ortho isomer (OPDA), which is the least toxic and most effective, caused substantial inhibition of growth of the Cloudman S91 mouse melanoma, the Harding-Passey mouse melanoma, and the Fortner hamster melanoma; and complete inhibition or regression of the Ehrlich solid carcinoma.