The Nature of the Effect of ACTH and Cortisone on Tumor Growth in Irradiated Animals

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Abstract
The anti-inflammatory effect of ACTH suggested its use for suppressing skin reactions in man following irradiation. It was shown that severe skin reaction due to x-radiation could be avoided or, if present, made to abate more rapidly by means of ACTH (25 mg./day) than by other forms of treatment. Since cortisone enhanced the lethal effect of x-rays (4) and increased the incidence of metastases of some experimental tumors (1, 2), a study of the mutual effect of these compounds and irradiation on experimental tumors seemed advisable. Material and Methods The following tumors and strains of mice were used: 1. C-1300 (neuroblastoma) in ABC mice 2. 15091-a (mammary carcinoma) in ABC mice 3. E 0771 (mammary carcinoma) in C57 B1 mice Transplantation of tumor fragments into the anterior chamber of the right eye of these strains produced almost 100 per cent “takes.” Under Nembutal anesthesia a dose of 3,000 r in air was administered through a 0.8-cm. field to the right orbit on the fourth day after transplantation. The factors were 140 kvp, 10 ma, no filter, 21 cm. focal skin distance, 461 r/min./air, h.v.l. 1.28 mm. Al. ACTH, 0.5 mg. dissolved in distilled water, or cortisone, 0.25 mg., was administered daily intraperitoneally. Administration of both drugs was started after tumor inoculation but prior to irradiation and was continued for fourteen, twenty, or forty-five days. Terramycin, 0.25 mg./ml., was added to the drinking water. Animals dying prior to the twenty-first day after transplantation as the result of the operation were discarded in the analysis of results. The tumor can be seen readily in the anterior chamber at three days after transplantation (Fig. 1, A). In unirradiated animals progressive tumor growth involves the orbit and often spreads into surrounding facial tissues by contiguity (Fig. 1, B). Only one tumor (C-1300) metastasizes regularly to the cervical lymph nodes. Irradiated animals reveal an area of alopecia around the orbit. The eye is usually cicatrized (Fig. 1, C). Recurrent tumor growth becomes apparent usually after the thirty-fifth day and leads to death prior to the seventieth day. Most animals which survive the period of observation are free of tumor. X-ray administration resulted in survival of 23 to 55 per cent of mice for seventy days. The time and dose factors of irradiation were chosen to allow observation of the effectiveness of drugs in producing either an increase or decrease in the number of seventy-day survivors (6). Results C-1300 in ABC Mice: C-1300 was the only tumor that metastasized regularly to the cervical lymph nodes in animals with persistent primary tumor growth in the orbit. All 47 control animals were dead by the fifty-sixth day. Though a few animals given cortisone survived up to the sixty-third day, neither cortisone nor ACTH produced any significant change in the survival time of unirradiated animals (Fig. 2 A). Following irradiation, 55 per cent of the animals survived for seventy days.

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