The Roles of Synthesis and Degradation in the Regulation of Catalase Levels in the Neoplastic Tissues

Abstract

Summary. Several rat hepatomas were analyzed as to their catalase activity. Ample enzyme activity was found in each of the following tumors : the HC-hepatoma and hepatomas No. 7316, 7794, 7800, H-139, and H-122. Moderate activity was also seen in the LC-hepatoma, in various lines of 5123 hepatoma, and in hepatomas No. H-35, 7288C, 7787, 7793, 7795, 9098, and 9108. The rapidly growing hepatomas, such as the Novikoff, and hepatomas No. 3683, and 3924A were virtually devoid of any activity. Attempts have been made at the measurement of the rate of catalase synthesis and degradation in neoplastic tissues, as well as in the tissues of the tumor-bearing hosts. Advantage was taken of the methods elaborated in our laboratory, based on the novel properties of certain inhibitors to irreversibly inactivate catalase, or to block its synthesis. Using 5123 hepatoma, it was determined that during each hour 3.88 units of catalase were being synthesized per gram of the host liver, as compared to 0.92 units in the tumor. During the same one-hour period 2.4% of the catalase molecules present were being destroyed in both types of tissues. In the case of 7316A hepatoma, there were only 2.30 units catalase formed in an hour which can be contrasted with 4.00 units in the host liver. The rates of destruction in the respective tissues were 2.6 and 1.9% per h. The kinetic studies endeavored in some of the other tumors, particularly the HC-hepatoma, were largely unsuccessful because of their failure to respond to the inhibitors. The lack of response to 3-amino-l,2,4-triazole may be related to absence or low activity of hydrogen peroxide producing oxidases within microbodies, absence of microbodies, or to low permeability of the microbody (or the cell) to the drug. Hepatoma 7794A does not contain typical microbodies.

Accumulation of Labelled Aminotriazole in Some Transplanted Tumours in Mice

“…An intriguing fact is that both tumours and aminotriazole have been found to produce a depression of catalase in several tissues but not in the erythrocytes (Heim, Appleman and Pyfrom, 1955;Rechcigle, Hruban and Morris, 1969). Whether this fact has any relation to the findings in the present study still remains to be investigated.…”

“…The reports of cancer incidence caused by aminotriazole prompted us to undertake an investigation of the distribution of the substance in mice (Tjalve, 1974 (Ullberg, 1954(Ullberg, , 1958, a procedure which includes sectioning of the animals on tape (20 ,m thick sections) in a microtome at -15°C, freeze drying the sections and mounting them on x-ray films to obtain autoradiograms.…”