Toxicity of a mixture of fatty acids on human blood lymphocytes and leukaemia cell lines.
The effect of a mixture of fatty acids upon lymphocyte and leukaemia cell death was examined. Peripheral lymphocytes from healthy subjects and two human leukaemia cell lines-Jurkat (T lymphocyte) and Raji (B lymphocyte) cells-were treated with increasing concentrations (0.1-0.4 mM) of a fatty acid mixture in a proportion mimicking that of the free fatty acids in plasma. Features of cell death were then evaluated. Phosphatidylserine externalization, and DNA fragmentation (apoptosis), and loss of cell membrane integrity (necrosis) and mitochondrial depolarization (common feature of cell death) were observed in leukaemia cells after the fatty acid treatment for up to 48 h. Human lymphocytes, however, when submitted to the same treatment presented apoptotic feature only. These findings indicate that a free fatty acid mixture (mimicking the proportion found in plasma) triggers apoptosis of leukaemia cell lines followed by loss of cell membrane integrity, whereas in human circulating lymphocytes the same treatment causes apoptosis only. Evidence is presented herein that mitochondria from leukaemic cells are more susceptible to the toxicity of the fatty acids than mitochondria from human circulating lymphocytes.
Otton
Rosemari
R
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524, 05508-900 Butantan, São Paulo, SP, Brazil. rose@icb.usp.br
Curi
Rui
R
D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000633:toxicity*; D006801:Humans; D007202:Indicators and Reagents; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology*; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D009336:Necrosis; D009707:Nucleosomes / Q000187:drug effects; D010718:Phosphatidylserines / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology
D005227:Fatty Acids; D007202:Indicators and Reagents; D009707:Nucleosomes; D010718:Phosphatidylserines