Environmental Health Perspectives 105, Supplement 5, September 1997

[ Citation in PubMed ] [ Related Articles ]

Crocidolite Asbestos Induces Apoptosis of Pleural Mesothelial Cells: Role of Reactive Oxygen Species and Poly(ADP-ribosyl) Polymerase

V. Courtney Broaddus, 1,2 Lin Yang, 1,2 Louis M. Scavo, 2 Joel D. Ernst, 1 and Alice M. Boylan 3

1 San Francisco General Hospital, San Francisco, California; 2 Cardiovascular Research Institute, University of California, San Francisco, California; 3 Medical University of South Carolina, Charleston, South Carolina

Abstract
Mesothelial cells, the progenitor cells 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. Rabbit pleural mesothelial cells were exposed to crocidolite asbestos or control particles (1-10 µg/cm 2 ) over 24 hr 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. Induction of apoptosis was dose dependent; crocidolite (5 µg/cm 2 ) induced apoptosis (15.0±1.1%, mean±SE; n=12) versus control particles (<4%), as measured by appearance of nuclear condensation. 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, and 3-aminobenzamide (an inhibitor of the nuclear enzyme, poly(adenosine diphosphate-ribosyl) polymerase). We conclude that asbestos induces apoptosis in mesothelial cells via reactive oxygen species. We speculate that escape from this pathway could allow the abnormal survival of mesothelial cells with asbestos-induced mutations. -- Environ Health Perspect 105(Suppl 5):1147-1152 (1997) Key words : oxygen radicals, annexin V, flow cytometry, deferoxamine, internalization

This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York. Manuscript received at EHP 26 March 1997; manuscript accepted 1 April 1997.

This work was supported in part by grants from the National Institutes of Health RO1 ESO6331 to V.C.B., Program Project Grant HL24075 to L.M.S., the American Heart Association, California Affiliate 93-209 to J.D.E., the National Institute of Environmental Health Sciences Clinical Investigator Award KO8 ES00253, and an American Lung Association research grant to A.M.B.

Address correspondence to Dr. V.C. Broaddus, Lung Biology Center, Box 0854, University of California, San Francisco, San Francisco General Hospital, San Francisco, CA 94143-0854. Telephone: (415) 206-3513. Fax: (415) 206-4123. E-mail: sfcourt@itsa.ucsf.edu

[ Table of Contents ] [ Full Article ] [ Citation in PubMed ] [ Related Articles ]

Last Update: October 16, 1997