The biogenesis of pentosenucleic acid pyrimidines in the Ehrlich ascites tumor.

Interest in the possibilities of utilizing the Ehr lich ascites tumor for studies of the intermediary metabolism of cancer tissues has been greatly stimulated in recent years by the important work of Klein (10) on the morphological and growth characteristics of these cells. Among the obvious advantages of ascites tumors over tumors growing in the solid form is the fact that one can easily obtain a known amount of rapidly growing tumor cells, with virtually no dead cells, which carry on their metabolic activity in vitro. Here as in other investigations on whole cells, interpretation of the results may be obscured by the selective permea bility of the cell. The degree of this effect on the cells of the ascites tumor has been demonstrated for amino acids by the work of Christensen (2). We have been interested in the biogenesis of PNA pyrimidines and have shown that orotic acid—an intermediate in the biogenesis of pyrim idines in rat liver (1)—is rapidly synthesized in vitro in rat liver slices (19, 21). Our studies (20, 21) and the work of Cooper and Wilson (4) on the for mation of orotic acid from small molecules, togeth er with investigations on the further fate of orotic acid by Hurlbert and Potter (8), ICornberg and associates (11, 16), and Hurlbert and Reichard (9), have established the following scheme for polynucleotide pyrimidine biogenesis in rat liver: