Document Detail

Silica-induced generation of extracellular factor(s) increases reactive oxygen species in human bronchial epithelial cells.
MedLine Citation:
PMID:  12011487     Owner:  NLM     Status:  MEDLINE    
Chronic inflammation and production of DNA-damaging reactive oxygen species (ROS) may be involved in silica-induced lung cancer. Studies to date have largely focused on silica-induced production of ROS by lung phagocytes. In this study, we investigated the hypothesis that particulate silica (DQ12) can also induce elevations in intracellular ROS in a cancer-target cell type, i.e., human bronchial epithelial cells (BECs), via an indirect mechanism that involves ROS-inducing extracellular factor(s) that occur upon the interaction of silica with culture medium. The intracellular production of hydrogen peroxide (H(2)O(2)) in BECs was assessed by flow cytometry via monitoring dichlorofluorescein (DCF) fluorescence. Culture medium containing 10% human serum was incubated with silica particles in concentrations ranging from 10 to 50 microg/ml, and following incubation for 1 h and removal of the particles, the resulting supernatants were added to BECs. Silica-treated medium induced significant increases in intracellular H(2)O(2) after the medium had been treated with as little as 10 microg/ml of the particles. Further, the level of ROS increases in BECs in response to silica-treated medium was found to be virtually identical to that induced in cells that were directly treated with silica in suspension. Based on enzyme inhibitory studies, the mechanism for this increased generation of intracellular ROS appears to involve both mitochondrial respiration and a NAD(P)H oxidase-like system. Spectrofluorimetric experiments with the antioxidant enzymes superoxide dismutase and catalase showed that superoxide anions (O2*-) and H(2)O(2) are generated in silica-treated medium, but these ROS do not fully account for the induction of the intracellular ROS response. Iron, on the other hand, was found to be crucial to the process. Our collective results suggest silica-aqueous medium interactions can lead to the generation of factor(s) that induce the intracellular production of potentially DNA-damaging ROS in BECs in a manner that does not require direct particle-cell interactions.
Alina Deshpande; Padma K Narayanan; Bruce E Lehnert
Related Documents :
24302777 - A multidisciplinary approach including the use of platelet-rich plasma to treat an elit...
18340017 - Mechanisms underlying caloric restriction and lifespan regulation: implications for vas...
14521937 - Involvement of reactive oxygen species and sp-1 in fibronectin production by oxidized ldl.
3038127 - Inhibition by nonsteroidal anti-inflammatory drugs of superoxide production and granule...
21396627 - Hemostasis alterations in patients with acute aortic dissection.
3036247 - Bryostatins mimic the effects of phorbol esters in intact human platelets.
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  67     ISSN:  1096-6080     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-05-15     Completed Date:  2002-10-10     Revised Date:  2010-09-17    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  275-83     Citation Subset:  IM    
Bioscience Division, MS M888, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Bronchi / drug effects*,  metabolism,  pathology
Catalase / pharmacology
Cells, Cultured
Culture Media, Conditioned / metabolism*,  pharmacology
Dose-Response Relationship, Drug
Epithelium / drug effects,  metabolism,  pathology
Free Radicals / metabolism*
Hydrogen Peroxide / metabolism
Mitochondria / drug effects,  enzymology
NADPH Oxidase / metabolism
Particle Size
Quartz / pharmacology*
Reactive Oxygen Species / metabolism*
Superoxide Dismutase / pharmacology
Grant Support
Reg. No./Substance:
0/Culture Media, Conditioned; 0/Free Radicals; 0/Reactive Oxygen Species; 14808-60-7/Quartz; 7722-84-1/Hydrogen Peroxide; EC; EC Dismutase; EC Oxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  2,3,7,8-tetrachlorodibenzo-p-dioxin interacts with endogenous estradiol to disrupt prostate gland mo...
Next Document:  Enhancement of nasal inflammatory and epithelial responses after ozone and allergen coexposure in Br...