Role of vasoactive amines in the antitumor activity of endotoxin.

To estimate a possible role of vasoamines in the antitumor action of endotoxin, effects of isoproterenol, serotonin and adrenaline on subcutaneously transplanted murine Meth A sarcoma and the capacity of these agents to elicit antitumor factors were studied. Macroscopically all agents induced tumor necrosis and a temporal tumor growth stop, but only endotoxin was capable of induction of complete tumor regression. Histology showed that all agents induced hyperemia by 4 h and hemorrhagic necrosis by 24 h. The latter was located superficially at the outside of tumors. Only serotonin and especially endotoxin induced substantial non-hemorrhagic necrosis in the remaining part of the tumors. Endotoxin induced a profound inhibition of the mitotic activity within the tumor, the effect of other agents was considerably less. Only endotoxin induced high levels of tumor necrosis factor, heat stable cytostatic factors and interferon in the circulation of mice treated with Corynebacterium parvum 14 days earlier. It is concluded that these and other data provide indirect but circumstantial evidence for a role of vasoamines in the induction of hyperemia and hemorrhagic necrosis by endotoxin. The latter two effects are probably causally related. It is suggested that non-toxic vasoamines may be useful adjuvants to other treatments of cancer.