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Neutrophils amplify the formation of DNA adducts by benzo[a]pyrene in lung target cells.
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MedLine Citation:
PMID:  9400705     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Inflammatory cells and their reactive oxygen metabolites can cause mutagenic effects in lung cells. The purpose of this study was to investigate the ability of activated neutrophils to modulate DNA binding of benzo[a]pyrene (B[a]P), a known carcinogen, in lung target cells. Equivalent numbers of rat lung epithelial cells (RLE-6TN cell line) and freshly isolated human blood neutrophils (PMN) were coincubated in vitro for 2 hr after addition of benzo[a]pyrene (0.5 microM) or two of its trans-diol metabolites, with or without stimulation with phorbol myristate acetate (PMA). DNA adducts of B[a]P-metabolites were determined in target cells using 32P-postlabeling; oxidative DNA damage (7-hydro-8-oxo-2'-deoxyguanosine [8-oxodG]) was evaluated by high performance liquid chromatography with electrochemical detection. Increased DNA adducts were observed in lung cells coincubated with polymorphonuclear leukocytes (PMN). Activation of PMN with PMA, or addition of more activated PMN in relation to the number of lung cells, further increased the number of adducts, the latter in a dose-response manner. Incubation with B[a]P-4,5-diol did not result in any adduct formation, while B[a]P-7,8-diol led to a significant number of adducts. Moreover, PMA-activated PMN strongly enhanced adduct formation by B[a]P-7,8-diol, but not 8-oxodG, in lung cells. The addition of antioxidants to the coincubations significantly reduced the number of adducts. Results suggest that an inflammatory response in the lung may increase the biologically effective dose of polycyclic aromatic hydrocarbons (PAHs), and may be relevant to data interpretation and risk assessment of PAH-containing particulates.
Authors:
P J Borm; A M Knaapen; R P Schins; R W Godschalk; F J Schooten
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Environmental health perspectives     Volume:  105 Suppl 5     ISSN:  0091-6765     ISO Abbreviation:  Environ. Health Perspect.     Publication Date:  1997 Sep 
Date Detail:
Created Date:  1998-01-30     Completed Date:  1998-01-30     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0330411     Medline TA:  Environ Health Perspect     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1089-93     Citation Subset:  IM    
Affiliation:
Department of Health Risk Analysis and Toxicology, Maastricht University, The Netherlands. p.borm@grat.unimaas.nl
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MeSH Terms
Descriptor/Qualifier:
Animals
Benzo(a)pyrene / toxicity*
Carcinogens / toxicity*
Cell Survival / drug effects
Cells, Cultured
Chromatography, High Pressure Liquid
DNA / analysis,  biosynthesis
DNA Adducts / biosynthesis*,  drug effects*
Deoxyguanosine / analogs & derivatives,  diagnostic use
Free Radical Scavengers
Lung / cytology*,  drug effects,  metabolism*
Neutrophils / metabolism*
Rats
Reactive Oxygen Species
Chemical
Reg. No./Substance:
0/Carcinogens; 0/DNA Adducts; 0/Free Radical Scavengers; 0/Reactive Oxygen Species; 50-32-8/Benzo(a)pyrene; 88847-89-6/8-oxo-7-hydrodeoxyguanosine; 9007-49-2/DNA; 961-07-9/Deoxyguanosine
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Environ Health Perspect
ISSN: 0091-6765
Article Information
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Print publication date: Month: 9 Year: 1997
Volume: 105 Issue: Suppl 5
First Page: 1089 Last Page: 1093
ID: 1470176
PubMed Id: 9400705

Neutrophils amplify the formation of DNA adducts by benzo[a]pyrene in lung target cells.
P J Borm
A M Knaapen
R P Schins
R W Godschalk
F J Schooten
Department of Health Risk Analysis and Toxicology, Maastricht University, The Netherlands. p.borm@grat.unimaas.nl



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