Asbestos induces apoptosis of human and rabbit pleural mesothelial cells via reactive oxygen species

Mesothelial cells, the progenitor cell of the asbestos-induced tumor mesothelioma, are particularly sensitive to the toxic effects of asbestos, although the molecular mechanisms by which asbestos induces injury in mesothelial cells are not known. We asked whether asbestos induced apoptosis in mesoth...

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Bibliographic Details
Published in:The Journal of clinical investigation 1996-11, Vol.98 (9), p.2050-2059
Main Authors: Broaddus, V C, Yang, L, Scavo, L M, Ernst, J D, Boylan, A M
Format: Article
Language:English
Subjects:
Animals
Annexin A5 - metabolism
Apoptosis
Asbestos - toxicity
Catalase - metabolism
Cell Division - drug effects
Cells, Cultured
Chelating Agents - chemistry
Deferoxamine - chemistry
DNA Fragmentation
Enzyme Inhibitors - pharmacology
Epithelial Cells
Epithelium - drug effects
Humans
Hypoxia - physiopathology
Pleura - cytology
Pleura - drug effects
Poly(ADP-ribose) Polymerase Inhibitors
Protein Binding
Rabbits
Reactive Oxygen Species
Superoxide Dismutase - metabolism
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Summary:Mesothelial cells, the progenitor cell of the asbestos-induced tumor mesothelioma, are particularly sensitive to the toxic effects of asbestos, although the molecular mechanisms by which asbestos induces injury in mesothelial cells are not known. We asked whether asbestos induced apoptosis in mesothelial cells and whether reactive oxygen species were important. Pleural mesothelial cells (rabbit or human) were exposed to asbestos (crocidolite, amosite, or chrysotile) or control particles at moderate doses (1-10 microg/cm2) over 24 h and evaluated for oligonucleosomal DNA fragmentation, loss of membrane phospholipid asymmetry, and nuclear condensation. Asbestos fibers, not control particles, induced apoptosis in mesothelial cells by all assays and induction of apoptosis was dose dependent for all types of asbestos, with crocidolite (5 microg/cm2) inducing 15.0+/-1.1% (mean+/-SE; n = 12) apoptosis versus control particles < 4%. Apoptosis induced by asbestos, but not by actinomycin D, was inhibited by extracellular catalase, superoxide dismutase in the presence of catalase, hypoxia (8% oxygen), deferoxamine, 3-aminobenzamide [an inhibitor of poly(ADP-ribosyl) polymerase], and cytochalasin B. Only catalase and cytochalasin B decreased fiber uptake. We conclude that asbestos induces apoptosis in mesothelial cells via reactive oxygen species. Escape from this pathway could allow the abnormal survival of mesothelial cells with asbestos-induced mutations.
ISSN:0021-9738
DOI:10.1172/jci119010