Metabolism of pyrimidine nucleotides in various tissues and tumor cells from rodents

The metabolism of pyrimidine nucleotides in various tissues and tumor cells of rodents was investigated. Ribonucleoside diphosphate reductase, thymidine monophosphate kinase and DNA polymerase (alpha, beta) were specifically localized in tumor cells, i.e., the activities of these enzymes in tumor cells were at least three times higher than those in normal tissues, including rapidly growing tissues, such as bone marrow, thymus, and spleen. The activities of deoxycytidine monophosphate deaminase and all the nucleoside kinase were high not only in tumor cells, but also in rapidly growing normal tissues, so that these enzymes are unsuitable as targets for cancer chemotherapy. The tissue distribution of other enzymes, including orotate phosphoribosyltransferases, cytidine triphosphate synthetase, thymidine monophosphate synthase, nucleoside phosphorylases and cytidine deaminase had no relation with the cell growth rate. AH130 tumor cells and the thymus showed specific increases in the activities of enzymes involved in de novo DNA synthesis. In contrast, Yoshida sarcoma and bone marrow showed high activities of enzymes in the salvage pathway of DNA synthesis, which suggested that the two tumors have different patterns of nucleotide metabolism.