The influence of stress and stress hormones on the transplantability of a non-immunogenic syngeneic murine tumor

Abstract

Quantitative transplantation assays of a syngeneic murine adenocarcinoma have been used to investigate the effects of stress hormones on tumor take probability. Cortisol, injected intraperitoneally one hour before and 3 hours after tumor cells, caused a dose dependent reduction of TD₅₀ (number of tumor cells required for 50% takes) by factors of from 4 at a total dose 4 Mμg/g to 68 at 400 μg/g. ACTH, given at 0.2 I.U. daily for 9 days spanning the time of tumor cell injection, reduced the TD₅₀ 2.5-fold, indicating that the peak gluco-corti-coid level achieved, rather than its duration, was of greater significance. Adrenaline, while much less effective than cortisol, produced an 8-fold reduction in TD₅₀ at its maximum tolerable dose. The effect of cortisol simulated that of whole body irradiation (WBI), and while both these agents depress immune reactivity, evidence is presented to suggest that immunological mechanisms are not responsible for their effect. WBI constitutes a systemic stress, and the demonstration that surgical trauma (laparotomy) could also reduce the TD₆₀ for this tumor suggested that both might act via endogenous glucocorticoids. However, the failure of prior total adrenalectomy of mice to abrogate the effect of either WBI or laparotomy indicated that stress hormones were not essential intermediaries. It is concluded that both stress hormones, especially glucocorticoids, and stressful procedures acting independently of stress hormones, can facilitate tumor transplantation.