Imperial College London
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ProfessorNagyHabib

Faculty of Medicine, Department of Surgery & Cancer

Professor of Hepatobiliary Surgery
 
 
 
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Contact

 

+44 (0)20 3313 8574nagy.habib

 
 
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Assistant

 

Mrs Benita White +44 (0)7960 986 387

 
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Location

 

BN1/18 B BlockHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Antonowicz:2021:10.1038/s41467-021-21800-5,
author = {Antonowicz, S and Bodai, Z and Wiggins, T and Markar, SR and Boshier, PR and Goh, YM and Adam, ME and Lu, H and Kudo, H and Rosini, F and Goldin, R and Moralli, D and Green, CM and Peters, CJ and Habib, N and Gabra, H and Fitzgerald, RC and Takats, Z and Hanna, GB},
doi = {10.1038/s41467-021-21800-5},
journal = {Nature Communications},
title = {Endogenous aldehyde accumulation generates genotoxicity and exhaled biomarkers in esophageal adenocarcinoma},
url = {http://dx.doi.org/10.1038/s41467-021-21800-5},
volume = {12},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Volatile aldehydes are enriched in esophageal adenocarcinoma (EAC) patients’ breath and could improve early diagnosis, however the mechanisms of their production are unknown. Here, we show that weak aldehyde detoxification characterizes EAC, which is sufficient to cause endogenous aldehyde accumulation in vitro. Two aldehyde groups are significantly enriched in EAC biopsies and adjacent tissue: (i) short-chain alkanals, and (ii) medium-chain alkanals, including decanal. The short-chain alkanals form DNA-adducts, which demonstrates genotoxicity and confirms inadequate detoxification. Metformin, a putative aldehyde scavenger, reduces this toxicity. Tissue and breath concentrations of the medium-chain alkanal decanal are correlated, and increased decanal is linked to reduced ALDH3A2 expression, TP53 deletion, and adverse clinical features. Thus, we present a model for increased exhaled aldehydes based on endogenous accumulation from reduced detoxification, which also causes therapeutically actionable genotoxicity. These results support EAC early diagnosis trials using exhaled aldehyde analysis.
AU  - Antonowicz,S
AU  - Bodai,Z
AU  - Wiggins,T
AU  - Markar,SR
AU  - Boshier,PR
AU  - Goh,YM
AU  - Adam,ME
AU  - Lu,H
AU  - Kudo,H
AU  - Rosini,F
AU  - Goldin,R
AU  - Moralli,D
AU  - Green,CM
AU  - Peters,CJ
AU  - Habib,N
AU  - Gabra,H
AU  - Fitzgerald,RC
AU  - Takats,Z
AU  - Hanna,GB
DO  - 10.1038/s41467-021-21800-5
PY  - 2021///
SN  - 2041-1723
TI  - Endogenous aldehyde accumulation generates genotoxicity and exhaled biomarkers in esophageal adenocarcinoma
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-021-21800-5
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000627410000002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/s41467-021-21800-5
UR  - http://hdl.handle.net/10044/1/93988
VL  - 12
ER  -
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