Diverse effects of camptothecin, an inhibitor of topoisomerase I, on the cell cycle of lymphocytic (L1210, MOLT-4) and myelogenous (HL-60, KG1) leukemic cells.
Exposure of mouse lymphocytic L1210 cells to 0.02-0.5 micrograms/ml of camptothecin (CAM) causes a slowdown in the rate of cell progression through S and G2 phases of the cell cycle; the "terminal" point of CAM action is about 1 h prior to mitosis. Some cells also enter higher DNA ploidy and progress through the cycle at that ploidy. CAM exerts similar effects (S- and G2-phase arrest, entrance to higher DNA ploidy, low initial cytotoxicity) on human lymphocytic MOLT-4 leukemia cells. In contrast, treatment of human promyelocytic HL-60 cells with CAM results in the immediate (occurring as early as 2 h after treatment) death of S- and G2+M-phase cells; the dead cells exhibit decreased DNA stainability with intercalating dyes, suggestive of DNA degradation. Although CAM is less cytotoxic to another human myelogenous leukemic cell line, KG1, the latter cells also respond like HL-60, namely by selective death in S and G2. The data indicate that there may be a tissue (leukemia type) specificity in the response of cells to camptothecin and suggest that myelogenous leukemias, especially those characterized by high proliferation rates, may be especially sensitive to the cytotoxic action of this and perhaps other topoisomerase I inhibitors.
Del Bino
G
G
Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Skierski
J S
JS
Darzynkiewicz
Z
Z
D000818:Animals; D002166:Camptothecin / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D007399:Interphase / Q000187:drug effects*; D007939:Leukemia L1210 / Q000473:pathology*; D007945:Leukemia, Lymphoid / Q000473:pathology*; D007951:Leukemia, Myeloid / Q000473:pathology*; D051379:Mice; D059004:Topoisomerase I Inhibitors; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D059004:Topoisomerase I Inhibitors; D002166:Camptothecin