Titre :

Endogenous aldehyde accumulation generates genotoxicity and exhaled biomarkers in esophageal adenocarcinoma

Auteur(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

Titre de la revue :

Nature Communications

Nom court de la revue :

Nat. Commun.

Numéro :

12

Pagination :

1454

Éditeur :

Springer Nature

Date de publication :

2021-03-05

ISSN :

2041-1723

Mot(s)-clé(s) en anglais :

DNA adducts
Metabolomics
Oesophageal cancer

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [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 ...
Lire la suite >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.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

INSERM
Université de Lille

Collections :

• Autres travaux scientifiques

Date de dépôt :

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