Abstract
Activated T cells lyse the murine renal cancer Renca. We have examined the mechanism of tumor cell lysis with the use of T cells derived from C57BL/6, BALB/c, B6.gld, and B6.Pfp-/- mice. C57BL/6 and BALB/c T cells can lyse Renca cells through the use of both granule- and Fas ligand (FasL)-mediated pathways. However, B6.gld T cells predominantly use granule-mediated killing, whereas B6.Pfp-/- T cells use FasL. The lysis of Renca by Pfp-/- T cells is only partially inhibited by the caspase inhibitor ZVAD-FMK, suggesting that caspase-independent signaling is also important for Renca cell lysis. When the reactive oxygen scavenger butylated hydroxyanisole was used alone or in combination with ZVAD-FMK a substantial reduction of Renca lysis was observed. Therefore, the caspase-independent generation of reactive oxygen intermediates in Renca after Fas triggering contributes to the lysis of these cells.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Chloromethyl Ketones / pharmacology
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Animals
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Apoptosis / physiology*
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Apoptosis Regulatory Proteins
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Butylated Hydroxyanisole / pharmacology
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Carcinoma, Renal Cell / immunology*
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Carcinoma, Renal Cell / pathology
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Caspases / physiology
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Crosses, Genetic
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Cytoplasmic Granules / metabolism
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Cytotoxicity, Immunologic
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Dipeptides / pharmacology
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Enzyme Inhibitors / pharmacology
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Fas Ligand Protein
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Free Radical Scavengers / pharmacology
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Humans
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Interferon-gamma / pharmacology
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Ketones / pharmacology
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Kidney Neoplasms / immunology*
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Kidney Neoplasms / pathology
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Lymphocyte Activation
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Reactive Oxygen Species
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Recombinant Proteins / pharmacology
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Signal Transduction / physiology*
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Specific Pathogen-Free Organisms
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T-Lymphocytes, Cytotoxic / immunology*
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TNF-Related Apoptosis-Inducing Ligand
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Transfection
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / pharmacology
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Tumor Necrosis Factor-alpha / physiology
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fas Receptor / genetics
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fas Receptor / physiology*
Substances
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Amino Acid Chloromethyl Ketones
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Apoptosis Regulatory Proteins
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Dipeptides
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Enzyme Inhibitors
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FASLG protein, human
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Fas Ligand Protein
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Fasl protein, mouse
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Free Radical Scavengers
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Ketones
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Membrane Glycoproteins
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Reactive Oxygen Species
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Recombinant Proteins
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TNF-Related Apoptosis-Inducing Ligand
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TNFSF10 protein, human
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Tnfsf10 protein, mouse
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Tumor Necrosis Factor-alpha
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benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
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fas Receptor
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MDL 201053
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Butylated Hydroxyanisole
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Interferon-gamma
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Caspases