The hepatocarcinogenicity of tannic acid.

In the group of chemical hepatocarcinogenic agents, the number of which has steadily increased in recent years (:$7), tannic acid deserves attention. Owing to its astringent effect, this compound was formerly used widely in therapy. The local treatment of thermal burns with tannic acid was suggested by Davidson (1935), and his procedure was generally employed in Hungary during World War II. I t was in the course of this war that the hepatotoxic action of tannic acid was recognized (1, 3, 4, 7, 36). Since the results of AngloSaxon scientific investigations were, on account of the war, unknown in Central Europe, nobody in Hungary was informed about the hepatotoxic effect of tannic acid before 1946. Liver damage and cirrhosis.--On the basis of comparative histologic examinations of the liver of individuals who had died of burns which were treated with tannic acid and/or untreated, we suspected the hepatotoxic effect of this substance as early as 1943-43. This suspicion was fully confirmed by animal experiments, but our results could not, because of the war, be presented before 1946, and the experiments had to be repeated, because our files had been lost for the same reason. I t was shown in those experiments that tannic acid is a selective poison of liver parenchyma, the effect of which manifests itself, depending on the dose and the route of administration, in acinocentral necrosis of varying extent. The disappearance of glycogen from the cytoplasm of liver cells is an early phenomenon, but it is not followed by fat ty degeneration (12). Next, we demonstrated the cirrhogenous effect ~f tannic acid. White rats were given repeatedly, a t intervals of several days, subcutaneous injections of tannic acid as a 1 per cent watery solution for the first ten doses, and thereafter as a 3 per cent solution, in graded doses of 10-70 mg/ra t . This treatment resulted in a gradual transformation of liver architecture (Fig. 1). In the early stages (up to the 40th day) breakdown and subsequent regeneration of the liver cells were the most striking features, with a frequent acinocentral collapse of the argentophilic fibrous meshwork. Another