The effects of 2-lysophosphatidylcholine (2-LPC), the alkyl
lysophospholipid derivatives (ALP)
1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) and 1-O-hexadecyl-sn-glycero-3-phospho-trimethyl-ammonio-hexanol, the 2-acetamide analog of
platelet-activating factor (PAF) 1-O-octadecyl-2-acetamide-sn-glycero-3-phosphocholine, the
thioether lysophospholipid derivative (TLP)
BM 41.440 and the
ether-linked lipoidal
amine CP-46,665 on tritiated
thymidine uptake and
trypan blue dye exclusion were tested in vitro in various freshly explanted cell samples from human nonneoplastic bone marrow and human
leukemias. In both assay systems, a dose range of 1-20 micrograms/ml of the compounds was tested after 24, 48 and 72 hr of coincubation with the cells. The
trypan blue dye exclusion revealed statistically significant preferential cytotoxicity in leukemic cells for three compounds with the order of quantitative selectiveness:
ET-18-OCH3 greater than BM41.440 greater than 2-acetamide analog of PAF.
CP-46,665 was the most toxic compound, but did not reveal significant differences between nonneoplastic bone marrow and leukemic cells when added in concentrations greater than 1 microgram/ml. The trimethyl-ammonio-
hexanol compound showed only minor activity in the majority of tests, when added at concentrations less than 20 micrograms/ml. 2-LPC was rather ineffective. The tritiated
thymidine uptake showed only preferential antiproliferative effects towards leukemic cells of
ET-18-OCH3 and, sometimes, within the dose time frame tested of
BM 41.440. All compounds tested except 2-LPC and the trimethyl-ammonio-
hexanol compound were active also in this assay (inhibition of uptake greater than 50% of the controls).(ABSTRACT TRUNCATED AT 250 WORDS)