Demonstration of Differences Between Normal and Tumor-Bearing Animals.

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Abstract
The simple experimental procedure reported can demonstrate a significant difference in response between certain tumor-bearing mice and their normal controls. The procedure involves challenging the 2 groups of animals with a lethal dose of a compound capable of reacting with the tumor or one of its metabolites. Either the cancerous or the normal animals may survive longer, depending upon both the type of tumor and the molecular configuration of the compound used. The difference in survival time between the tumor-bearing and normal animals is thought due to a modification of the toxicity of the administered compound following reaction with a tumor component. The Cloudman S91 mouse melanoma was employed as the primary model since some of the chemistry of its metabolites is known. For example, p-phenylene- diamine (PPDA) combines in vitro with dihydroxyphenylalanine (DOPA) to yield an oxygen-consuming, pigment-producing reaction. DOPA is an assumed component produced in the biochemical chain of events in the metabolism of pigmented melanomas, and thus a rational foundation is provided for an in vivo reaction when PPDA is administered to melanoma-bearing animals. The consequence of this procedure, with the above combination, is a significant difference in the mean survival times of the two groups with a protective effect provided by the presence of the tumor. This phenomenon can be inverted by altering the administered compound or by employing a different histological or physiological type of tumor, in which event the tumor may become a biochemical liability to the host. Implications of possible utility in the study of the biochemistry of tumors and in chemotherapy are discussed.