Berube, Kelly Ann ![]() |
Abstract
Asbestos causes protracted, dose-dependent increases in steady-state mRNA levels of the proto-oncogenes c-fos and c-jun, and AP-l DNA-binding activity in normal rat pleural mesothelial (RPM) cells (I). To determine the phenotypic end points of overexpression of these early response genes by asbestos, both cell proliferation and apoptosis were examined in confluent RPM cells exposed to a range of concentrations (1.25 to 10 p.g/cm' dish) of crocidolite asbestos for 24 and 48 h. Quantitation of RPM cells pulsed with 5-bromo-2'-deoxyuridine revealed that asbestos caused dose-dependent decreases in cells undergoing DNA synthesis. Decreases in cell proliferation were accompanied by dose-related increases in apoptosis using (l) terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (i.e., ApopTag technique), (2) 4',6-diamidino-2-phenylindole cell staining, and (3) fluorescent-activated cell sorter after incorporation of propidium iodide. Less striking but significant dose-related increases in apoptosis were observed in RPM cells exposed to H20, (300 p.M), and no apoptosis was seen after exposure of cells to high concentrations (10 p.g/cm' dish) of glass beads. Our results are unique in that they demonstrate that asbestos induces apoptosis in mesothelial cells at concentrations eliciting increased expression of the proto-oncogenes c-fos and c-jun.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Biosciences |
Subjects: | Q Science > QH Natural history > QH301 Biology Q Science > QP Physiology |
Publisher: | American Thoracic Society |
ISSN: | 1044-1549 |
Last Modified: | 24 Oct 2022 10:17 |
URI: | https://orca.cardiff.ac.uk/id/eprint/43691 |
Citation Data
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