Endogenous aldehyde accumulation generates ...
Type de document :
Article dans une revue scientifique: Article original
PMID :
URL permanente :
Titre :
Endogenous aldehyde accumulation generates genotoxicity and exhaled biomarkers in esophageal adenocarcinoma
Auteur(s) :
Antonowicz, Stefan S. [Auteur]
Bodai, Zsolt [Auteur]
Wiggins, Tom [Auteur]
Markar, Sheraz R. [Auteur]
Boshier, Piers R. [Auteur]
Goh, Yan Mei [Auteur]
Adam, Mina E. [Auteur]
Lu, Haonan [Auteur]
Kudo, Hiromi [Auteur]
Rosini, Francesca [Auteur]
Goldin, Robert [Auteur]
Moralli, Daniela [Auteur]
Green, Catherine M. [Auteur]
Peters, Chris J. [Auteur]
Habib, Nagy [Auteur]
Gabra, Hani [Auteur]
Fitzgerald, Rebecca C. [Auteur]
Takats, Zoltan [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Hanna, George B. [Auteur]
Bodai, Zsolt [Auteur]
Wiggins, Tom [Auteur]
Markar, Sheraz R. [Auteur]
Boshier, Piers R. [Auteur]
Goh, Yan Mei [Auteur]
Adam, Mina E. [Auteur]
Lu, Haonan [Auteur]
Kudo, Hiromi [Auteur]
Rosini, Francesca [Auteur]
Goldin, Robert [Auteur]
Moralli, Daniela [Auteur]
Green, Catherine M. [Auteur]
Peters, Chris J. [Auteur]
Habib, Nagy [Auteur]
Gabra, Hani [Auteur]
Fitzgerald, Rebecca C. [Auteur]
Takats, Zoltan [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Hanna, George B. [Auteur]
Titre de la revue :
Nature Communications
Nom court de la revue :
Nat. Commun.
Numéro :
12
Pagination :
-
Date de publication :
2021-03-05
ISSN :
2041-1723
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 >
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
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
INSERM
Université de Lille
Université de Lille
Date de dépôt :
2022-06-15T13:58:10Z
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