ALKYLPHOSPHOCHOLINES - EFFECTS ON HUMAN LEUKEMIC-CELL LINES AND NORMAL BONE-MARROW CELLS

The anti-leukemic activity of a series of alkylphosphocholines (APCs) was studied against a panel of human leukemic cell lines (HL-60, K-562 , Reh, MOLT-4, Jurkat, Ramos and Fail), Cytotoxic efficacy was measure d by the MTT cell survival assay. All cell lines were found to be sens itive, except the multipotential CML-derived K-562 cell line. Flow cyt ometry of HL-60 cells showed a significant decrease of cells in S phas e and the formation of a sub-G(1) fraction. DNA fragmentation typical for programmed cell death was detected by DNA gel electrophoresis in t hese cells but not in any of the other leukemic lines, At concentratio ns below the cytotoxic range, mitogenic effects were seen in HL-60 cel ls after 14-hr exposure. Colony formation by K-562 cells revealed an a ugmented clonogenicity after exposure to APC with a shout alkyl chain. in contrast, cells of lymphoid origin did not undergo DNA fragmentati on or show mitogenic stimulation after exposure to APC, Normal bone ma rrow cells were also investigated for mitogenic and genotoxic effects, No decrease was found in the number of hematopoietic progenitors in l ong-term bone marrow cell cultures after exposure to APC, On the contr ary, a significant increase was found after short exposure. Dodecylpho sphocholine, hexadecylphosphocholine (HPC) and octadecyl-[2-(N-methylp iperidino)-ethyl]-phosphate exhibited a mild clastogenicity at equimol ar high doses on murine bone marrow cells in vivo, which is unusual fo r the majority of classical DNA-interacting anti-cancer drugs, In conc lusion, APCs are agents with a broad spectrum of in vitro anti-leukemi c: effects, which lack hematological toxicity. (C) 1998 Wiley-Liss, In c.