Effects of conditioned medium upon proliferation, deoxynucleotide metabolism, and antimetabolite sensitivity of promyelocytic leukemic cells in vitro.
In order to investigate the interaction of factors from leukocyte-conditioned medium with leukemic cells, effects of an ammonium sulfate-precipitated conditioned medium concentrate were tested upon HL-60 cells. This preparation increased tritiated thymidine incorporation into DNA of HL-60 cells markedly, an effect which was found to be attributable in large part to greater thymidine accumulation in the intracellular nucleotide triphosphate pool. A modestly expanded population of DNA synthetic phase cells was also demonstrated by flow cytometry. Similar effects were noted of the K562 and KG-1 cell lines and were also demonstrable with giant cell tumor-conditioned medium. These effects were not demonstrable with a purified preparation of granulocyte-monocyte colony-stimulated factor. Because of the altered pattern of nucleotide metabolism noted, the effect of the conditioned medium concentrate upon 5-fluorouracil sensitivity was tested. Following continuous 24-h exposure to 5-fluorouracil at 5 X 10(-6) M, tritiated thymidine incorporation of HL-60 cells increased in parallel with depletion of endogenous thymidylate. Conditioned medium concentrate markedly sensitized cells to this effect of 5-fluorouracil and also increased growth retardation, cytotoxicity, and cell cycle arrest as assessed by flow cytometry. These studies thus demonstrated marked effects of a factor in conditioned medium on deoxynucleotide uptake and metabolism of the HL-60 line. These effects occurred in conjunction with, but were relatively more marked than, effects upon cell cycle distribution and were found to influence chemotherapy sensitivity.
D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D003854:Deoxyribonucleotides / Q000378:metabolism*; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D009000:Monocytes / Q000502:physiology*
D003470:Culture Media; D004273:DNA, Neoplasm; D003854:Deoxyribonucleotides; D006133:Growth Substances; D005472:Fluorouracil