The behavior of dihydrouracil dehydrogenase activity (4,5-dihydrouracil:NADP oxidoreductase, EC 188.8.131.52) was compared in proliferating normal liver (from developing rats and from partially hepatectomized rats) and in neoplastic liver (spectrum of hepatomas of different growth rates). The enzyme activity was determined in the 100,000Xgsupernatant fluid. The affinity of the enzyme to the substrate, uracil, was similar in the hepatomas to that in the liver of control normal rats of the same strain. The pH optimum of the control and neoplastic livers was at 7.2. The activities of dihydrouracil dehydrogenase in rat liver, thymus, intestinal mucosa, spleen, kidney, brain, skeletal muscle, and heart were 2.0, 1.1, 0.9, 0.7, 0.6, 0.4, 0.2, and 0.1 μmoles/hr/g, wet weight, of tissue at 37°, respectively. In the differentiating liver, the enzyme activity of the average cell increased 2.7-fold from the level observed in the newborn to reach the activity of the liver of adult rat. In the regenerating liver at 24 hr after partial hepatectomy, the enzyme activity decreased to 74% of that of the sham-operated controls. In the spectrum of hepatomas, dihydrouracil dehydrogenase activity decreased in parallel with the increase in hepatoma growth rate. In the most rapidly growing tumors (9618A2, 3683F), the activities were about 15% or less of those in liver of control rats of the same strain, sex, age, and weight. Since the regenerating liver proliferates at a rate comparable to that of the rapidly growing hepatoma, the marked decrease observed in the tumor appears to be specific to neoplastic cell growth. Dihydrouracil dehydrogenase is considered the rate-limiting enzyme in the catabolic pathway of uracil therefore, the close linking of the decrease in the activity of this enzyme with the increase in hepatoma growth rate provides further evidence in support of the Molecular Correlation Concept.
|Original language||English (US)|
|Number of pages||6|
|State||Published - Jul 1971|
ASJC Scopus subject areas
- Cancer Research