Imperial College London
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DrCandiceRoufosse

Faculty of Medicine, Department of Immunology and Inflammation

Clinical Reader in Renal Pathology
 
 
 
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Contact

 

+44 (0)20 3313 3280c.roufosse

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Arlt:2015:toxsci/kfv086,
author = {Arlt, VM and Krais, AM and Godschalk, RW and Riffo-Vasquez, Y and Mrizova, I and Roufosse, CA and Corbin, C and Shi, Q and Frei, E and Stiborova, M and van, Schooten F-J and Phillips, DH and Spina, D},
doi = {toxsci/kfv086},
journal = {Toxicological Sciences},
pages = {213--225},
title = {Pulmonary inflammation impacts on CYP1A1-mediated respiratory tract DNA damage induced by the carcinogenic air pollutant benzo[a]pyrene},
url = {http://dx.doi.org/10.1093/toxsci/kfv086},
volume = {146},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Pulmonary inflammation can contribute to the development of lung cancer in humans. We investigated whether pulmonary inflammation alters the genotoxicity of polycyclic aromatic hydrocarbons (PAHs) in the lungs of mice and what mechanisms are involved. To model nonallergic acute inflammation, mice were exposed intranasally to lipopolysaccharide (LPS; 20 µg/mouse) and then instilled intratracheally with benzo[a]pyrene (BaP; 0.5 mg/mouse). BaP-DNA adduct levels, measured by 32P-postlabeling analysis, were approximately 3-fold higher in the lungs of LPS/BaP-treated mice than in mice treated with BaP alone. Pulmonary Cyp1a1 enzyme activity was decreased in LPS/BaP-treated mice relative to BaP-treated mice suggesting that pulmonary inflammation impacted on BaP-induced Cyp1a1 activity in the lung. Our results showed that Cyp1a1 appears to be important for BaP detoxification in vivo and that the decrease of pulmonary Cyp1a1 activity in LPS/BaP-treated mice results in a decrease of pulmonary BaP detoxification, thereby enhancing BaP genotoxicity (ie, DNA adduct formation) in the lung. Because less BaP was detoxified by Cyp1a1 in the lungs of LPS/BaP-treated mice, more BaP circulated via the blood to extrapulmonary tissues relative to mice treated with BaP only. Indeed, we observed higher BaP-DNA adduct levels in livers of LPS/BaP-treated mice compared with BaP-treated mice. Our results indicate that pulmonary inflammation could be a critical determinant in the induction of genotoxicity in the lung by PAHs like BaP. Cyp1a1 appears to be involved in both BaP bioactivation and detoxification although the contribution of other enzymes to BaP-DNA adduct formation in lung and liver under inflammatory conditions remains to be explored.
AU  - Arlt,VM
AU  - Krais,AM
AU  - Godschalk,RW
AU  - Riffo-Vasquez,Y
AU  - Mrizova,I
AU  - Roufosse,CA
AU  - Corbin,C
AU  - Shi,Q
AU  - Frei,E
AU  - Stiborova,M
AU  - van,Schooten F-J
AU  - Phillips,DH
AU  - Spina,D
DO  - toxsci/kfv086
EP  - 225
PY  - 2015///
SN  - 1096-0929
SP  - 213
TI  - Pulmonary inflammation impacts on CYP1A1-mediated respiratory tract DNA damage induced by the carcinogenic air pollutant benzo[a]pyrene
T2  - Toxicological Sciences
UR  - http://dx.doi.org/10.1093/toxsci/kfv086
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000359630300002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/63106
VL  - 146
ER  -
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