Purine biosynthesis de novo in mouse tissues and a mouse tumor.

There is evidence that an interchange of purines among tissues may occur (1, 2) and that, for example, bone marrow obtains its purines from the liver (3). For this reason relative rates of purine synthesis de novo in organs, as indicated by incorporation of a radioactive precursor, may be ambiguous if measured at relatively long times after administration of the precursor. Therefore the synthesis de novo of purines was measured in mouse tissues at short time intervals after radioisotope injection. This process was also studied in slices of the same tissues in vitro. Harrington and Lavik (4) and Smellie et al. (5, 6) formerly reported the inability of Ehrlich carcinoma ascites cells, in vitro, to carry on rapid purine synthesis de novo, contrary to reports from LePage and co-workers (7-10). The conditions used by the various investigators have differed. More recently, Thompson et al. (11) have increased the rate of purine synthesis de nova in these cells by the addition of glucose to the medium, confirming the findings of LePage (7). The effect of liver extract, which also stimulated this process, was not, however, completely duplicated by glucose. Recently, Harrington has also noted a marked stimulation of purine synthesis by glucose, and interprets this in terms of ribose synthesis (12). In the experiments of Smellie et al. (6) and Thompson et al. (11) some differences were noted in the behavior of formate and glycine in purine synthesis de novo. This paper presents studies on factors influencing purine synthesis de novo in Ehrlich carcinoma ascites cells in vitro. The mechanism of the stimulation of this process by glucose has been investigated, and the stimulatory effect of glutamine, a compound which is known to be a precursor of nitrogen atoms 3 and 9 of the purine ring (13, 14), is confirmed. The behavior of formate and glycine in the synthetic process has been studied and an explanation for the differences between them is tendered.