Effects of Dinitrophenol on an Experimental Sarcoma of the White Rat. ∗

Abstract

Recent studies of the effect of dinitrophenol on metabolism 1 have prompted us to study its effect upon tumor growth. Since it is known that the metabolism of the cell of malignant neoplasms is more active than that of the normal cell, we were curious to learn whether or not dinitrophenol administered either by injection or mixed with the food would demonstrably affect the activity of the neoplastic cell. The tumor material utilized in this study is a fibrosarcoma which kills white rats in from 30 to 60 days. It was derived from a transplantable fibroma by intensive inbreeding. The fibroma, in turn, is a derivative from the mammary adenofibroma of the white rat. The sarcoma is non-metastatic but recurs locally for indefinite periods. It otherwise behaves like a malignant tumor of connective tissue origin.

Thirty white rats varying in age from 84 to 110 days were divided into 6 equal groups and implanted with a sarcoma from the same donor. Two groups were left untreated for controls. Two groups were injected twice daily, with 15 mg. per kg. body weight of alpha-dinitrophenol, the dose being increased when necessary to produce a maximum temperature rise of 2°C. One of these 2 groups was injected from the time of implantation and the other 14 days after the implant was made, or 2 days after active growth was apparent. One group was injected with 1% sodium bicarbonate, the solvent used in making the solution of dinitrophenol, and one group was fed stock diet to which had been added dinitrophenol in the concentration of 1:1000 (daily dose of dinitrophenol ingested about 43 mg. per kg.). The period of observation was between 3 and 4 weeks. The following results were obtained:

Gross Changes. As was to be expected, the average gain of body weight of all dinitrophenol-treated animals was retarded. The tumors of animals fed dinitrophenol grew with about the same speed as those of the controls. Animals injected with dinitrophenol from the time of implantation showed a slight retardation of growth of the tumor when compared to tumors in animals injected after the implant had begun to grow actively. On gross examination, neither group showed any remarkable changes not observed in the controls or animals injected with sodium bicarbonate.

Conclusions. Dinitrophenol did not affect maeroscopically the growth of an experimental sarcoma in rats, but microscopically there were evidences of increased vascularity and destructive cellular changes, whose significance remains undetermined.