Effects of alkyl-lysophospholipids on human leukemic cell lines measured by nuclear magnetic resonance.
Part of the cytotoxic action of alkyl-lysophospholipids (ALP) on leukemic cells is known to result from the lack of an O-alkyl cleavage enzyme and its antimetabolic effect which results in a toxic lysophospholipid buildup. Further, ALP (5 micrograms/ml) suppresses clonogenicity and tritiated thymidine uptake in HL60 cultures after 24 hr of exposure. The effect of ALP on two leukemic cell lines, HL60 and K562, measured by two nuclear magnetic resonance (NMR) techniques and examined by electron microscopy is reported. 31P-NMR spectroscopy indicates that the adenosine 5'-triphosphate:adenosine 5'-diphosphate ratios are unaffected after 24 hr, as is mitochondrial morphology, judging by electron micrographs. However, cell membrane integrity in HL60 is altered at that time. The earliest ALP effects occur in NMR internal water relaxation at 1 hr after ALP exposure, followed by a small reduction in tritiated thymidine uptake at 4 hr. No effect is observed in K562 cell cultures in morphology or NMR measurements. No new 31P-labeled metabolites were detected in either cell line as a result of drug treatment.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D002460:Cell Line; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute / Q000503:physiopathology* / Q000648:ultrastructure; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008246:Lysophospholipids; D009682:Magnetic Resonance Spectroscopy; D008854:Microscopy, Electron; D010743:Phospholipids / Q000494:pharmacology*
D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D010743:Phospholipids; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate