In vitro and in vivo inhibition of catalase by uric acid and other nucleic acid catabolites.

Early in this century it was observed that aqueous extracts of animal tissues were capable of inhibiting the activity of catalase in vitro (~). More recently it has been found that either normal adult or growing tissues are very rich in catalase-inhibitory substances (1, 7). I n vivo experiments showed tha t the catalase activity of the liver of rats and mice bearing tumors was 50 per cent of tha t in normal animals (8). Hargreaves and Deutsch (10) subsequently demonstrated in the homogenate of transplantable tumors the presence of a thermostable fraction capable of inhibiting in vitro preparations of crystalline catalase and also the activity of normal rat liver homogenates. These observations have been confirmed (13, 14). Seabra and Deutsch (19) obtained data to show that post-mortem autolysis of normal ox liver caused the production of a large amount of inhibitory substances. I n vivo experiments showed that extracts of normal tissues, of spleen in particular, were able to depress liver catalase activity when the extracts were injected under proper conditions in living animals (5). I t is evident, therefore, tha t both cancerous and normal tissues contain substances capable of inhibiting catalase activity. Necrosis in cancerous tissues and post-mortem autolysis in normal ones liberate large quantities of these substances. Furthermore, Luck6 and collaborators (16) showed, in parabiotic animals, that the substances responsible for the depression of the catalase activity could be transferred from a carcinomatous rat to a normal one through the circulating blood. Hargreaves, Lobo, and Seabra (11) showed that these inhibitory substances are cleared via the kidneys and passed to the urine. Having obtained this fraction either from cancerous patients or from normal subjects, the authors concluded that