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Cytotoxic effects of ether lipids and derivatives in human nonneoplastic bone marrow cells and leukemic cells in vitro
Author(s) -
Schick Hans D.,
Berdel Wolfgang E.,
Fromm Michael,
Fink Ulrich,
Jehn Ulrich,
Ulm Kurt,
Reichert Anneliese,
Eibl Hansjörg,
Unger Clemens,
Rastetter Johann
Publication year - 1987
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02535552
Subject(s) - trypan blue , chemistry , microbiology and biotechnology , in vitro , bone marrow , cytotoxicity , phosphocholine , biochemistry , ether , cytotoxic t cell , phospholipid , immunology , phosphatidylcholine , biology , organic chemistry , membrane
The effects of 2‐lysophosphatidylcholine (2‐LPC), the alkyl lysophospholipid derivatives (ALP) 1‐ O ‐octadecyl‐2‐ O ‐methyl‐ rac ‐glycero‐3‐phosphocholine (ET‐18‐OCH 3 ) 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 μg/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‐OCH 3 >BM41.440>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 μg/ml. The trimethyl‐ammoniohexanol compound showed only minor activity in the majority of tests, when added at concentrations <20 μg/ml. 2‐LPC was rather ineffective. The tritiated thymidine uptake showed only preferential antiproliferative effects towards leukemic cells of ET‐18‐OCH 3 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>50% of the controls). Based on these results, ET‐18‐OCH 3 and BM 41.440 are recommended for experimental bone marrow purging.