Metabolic activities of murine carcinoma 755 at various stages of growth.

Summary The rates of synthesis of RNA and DNA decreased as murine Carcinoma 755 increased in size during a period of 26 days. The rates of synthesis were determined by measuring the incorporation of thymidine-methyl- 3 H into the acid-insoluble fractions in vivo , of thymidine-2- 14 C into the acid-insoluble fractions of minced tumors in vitro , and of formate- 14 C and adenine-8- 14 C into both the acid-insoluble fractions and the isolated adenine and guanine of RNA and DNA in vivo . These decreasing rates of synthesis in growing tumors correlated well with the decreasing proliferative fractions previously reported by others. The quantities of soluble metabolites formed in vivo by the tumors following the administration of formate- 14 C or adenine-8- 14 C decreased as the tumors enlarged. The decreases in the formation of amino acids (primarily serine), carboxylic acids (primarily lactic acid), and purine-containing soluble compounds lagged behind decreases in RNA and DNA synthesis. It is unlikely that the decline in incorporation of the substrate into soluble and insoluble components is due entirely to decreased vascularization of the larger tumors, because similar decreases of incorporation of thymidine-2- 14 C into acid-insoluble compounds occurred during in vitro incubation of minced tumors. The DNA polymerase activity of crude, cell-free preparations from tumors increased to a maximum for 14-day-old tumors and decreased thereafter. The lower incorporation of radioactive substrate into acid-insoluble material by preparations of the older tumors was not due to deficiencies of thymidylate kinase or limited pools of dTTP. Information about the sizes of the generated pools of the other necessary deoxyribonucleoside triphosphates is not available, but a maximum of polymerase activity was observed for the 14-day-old tumor preparation, even when all 4 of the deoxyribonucleoside triphosphates were added to the incubation mixtures. The rates of synthesis of RNA and DNA in the spleens and marrows of the host animals increased with increasing tumor size, while there was relatively little change in the rates of synthesis of RNA and DNA in the livers, kidneys, lungs, and brains.