Title :

Endogenous aldehyde accumulation generates genotoxicity and exhaled biomarkers in esophageal adenocarcinoma

Author(s) :

Antonowicz, Stefan S. [Auteur]
Imperial College London
Bodai, Zsolt [Auteur]
Imperial College London
Wiggins, Tom [Auteur]
Imperial College London
Markar, Sheraz R. [Auteur]
Imperial College London
Boshier, Piers R. [Auteur]
Imperial College London
Goh, Yan Mei [Auteur]
Imperial College London
Adam, Mina E. [Auteur]
Imperial College London
Lu, Haonan [Auteur]
Imperial College London
Kudo, Hiromi [Auteur]
Imperial College London
Rosini, Francesca [Auteur]
Imperial College London
Goldin, Robert [Auteur]
Imperial College London
Moralli, Daniela [Auteur]
The Wellcome Trust Centre for Human Genetics [Oxford]
Green, Catherine M. [Auteur]
The Wellcome Trust Centre for Human Genetics [Oxford]
Peters, Chris J. [Auteur]
Imperial College London
Habib, Nagy [Auteur]
Imperial College London
Gabra, Hani [Auteur]
Imperial College London
Fitzgerald, Rebecca C. [Auteur]
University of Cambridge [UK] [CAM]
Takats, Zoltan [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Imperial College London
Hanna, George B. [Auteur]
Imperial College London

Journal title :

Nature Communications

Abbreviated title :

Nat. Commun.

Volume number :

12

Pages :

1454

Publisher :

Springer Nature

Publication date :

2021-03-05

ISSN :

2041-1723

English keyword(s) :

DNA adducts
Metabolomics
Oesophageal cancer

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

INSERM
Université de Lille

Collections :

• Autres travaux scientifiques

Submission date :

2022-06-15T13:58:10Z
2023-03-24T08:57:16Z