mycophenolic-acid and Leukemia--Lymphoid

In a previous report we demonstrated in mouse lymphoma (S-49) cells that DNA synthesis inhibition resulting from guanine starvation is associated with GTP rather than dGTP depletion. Since several effective anticancer drugs act via guanine depletion, it is important to test whether critical GTP depletion is unique to S-49 cells or also occurs in other cell lines. Mycophenolic acid-induced guanine starvation caused a drastic DNA synthesis inhibition in the human lymphoblastic T leukemia (CEM) and the mouse B leukemia (L1210) cell lines, which was again associated with GTP depletion rather than dGTP depletion. These results suggest that GTP depletion represents a common target of purine antimetabolites in mammalian cells.

Topics: Animals; Cell Division; Deoxyguanosine; DNA, Neoplasm; Guanosine; Guanosine Triphosphate; Humans; Leukemia L1210; Leukemia, Lymphoid; Mice; Mycophenolic Acid

Topics: Animals; Antimetabolites; Cell Line; Cell Survival; Deoxyribonucleosides; Deoxyribonucleotides; DNA, Neoplasm; Drug Synergism; Drug Tolerance; Guanine Nucleotides; Guanosine; Inosine; Leukemia, Experimental; Leukemia, Lymphoid; Mercaptopurine; Mycophenolic Acid; Ribonucleotides; RNA, Neoplasm; Stimulation, Chemical; Sulfides; Sulfur Radioisotopes; Thioguanine

Topics: Administration, Oral; Adult; Aged; Antibiotics, Antineoplastic; Caproates; Carcinoma; Esophageal Neoplasms; Female; Hodgkin Disease; Humans; Injections, Intraperitoneal; Injections, Intravenous; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Multiple Myeloma; Mycophenolic Acid; Stomach Neoplasms