Failure of Phenoxybenzamine to Prevent Formation of Hepatomas After Chronic Carbon Tetrachloride Administration

Summary

Several pharmacological agents affecting the response of animals to the sympathetic neurohumors, epinephrine and levarterenol, were screened for their ability to prevent acute hepatic damage due to carbon tetrachloride (CCl₄) in C3H mice. The vasodilator, mannitol hexanitrate, was ineffective as was the adrenergic blocking agent, ergotamine. Ephedrine potentiated the acute hepatotoxic effects of CCl₄. Phenoxybenzamine (Dibenzyline) and reserpine were effective in reducing the hepatotoxicity of CCl₄. Phenoxybenzamine was chosen for use in a chronic experiment designed to demonstrate whether adrenergic blockade with this agent would prevent the formation of hepatomas in C3H mice chronically treated with CCl₄. At the doses tested there was no evidence of protection against hepatoma formation.—J Nat Cancer Inst 30: 837–843, 1963.