Effect of adrenoceptor blockade on hemorrhagic necrosis of meth A sarcomata induced by endotoxin or tumor necrosis serum.
An intravenous injection of endotoxin into BALB/c mice bearing subcutaneous Meth A sarcomata caused hemorrhagic necrosis and reduced growth of the tumors. In a number of instances this was followed by regression. alpha-Adrenergic blockade with phentolamine prior to endotoxin did not influence tumor growth, but tended to reduce the incidence of regression when compared to mice merely treated with endotoxin. The frequency of hemorrhagic necrosis was not changed, although the extent of necrosis was somewhat reduced. The alpha-adrenoceptor blocking agent phenoxybenzamine nullified the growth retardation induced by endotoxin and reduced the frequency of regression. Moreover both incidence and extent of necrosis were diminished. Beta-adrenoceptor blockade with propranolol seems to potentiate the effect of endotoxin on tumor growth in the highest dose, but had no substantial effect on the necrotizing activities of endotoxin. Both alpha-blocking agents impaired induction of hemorrhagic necrosis and nullified tumor growth inhibition by tumor necrosis serum (TNS). beta-Adrenoceptor blockade decreased only the incidence of necrosis induced by TNS. Regressing tumors had considerably more hemorrhagic necrosis irrespective of pretreatment, excepted phenoxybenzamine. A single injection of the latter agent caused a dose-dependent stimulation of tumor growth, while the other agents exerted no effect. It is suggested that both normal and endotoxin-modified tumor growth are under alpha-adrenergic control and that induction of hemorrhagic necrosis is possibly mediated by release of adrenal catecholamines.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology / Q000473:pathology*; D007106:Immune Sera / Q000494:pharmacology; D051379:Mice; D009336:Necrosis; D009368:Neoplasm Transplantation; D010646:Phentolamine / Q000494:pharmacology*; D011425:Propionibacterium acnes; D011433:Propranolol / Q000494:pharmacology*; D012513:Sarcoma, Experimental / Q000276:immunology / Q000473:pathology*
D004731:Endotoxins; D007106:Immune Sera; D011433:Propranolol; D010646:Phentolamine