Endogenous aldehyde accumulation generates genotoxicity and exhaled biomarkers in esophageal adenocarcinoma

Stefan Antonowicz, Zsolt Bodai, Tom Wiggins, Sheraz R. Markar, Piers R. Boshier, Yan Mei Goh, Mina E. Adam, Haonan Lu, Hiromi Kudo, Francesca Rosini, Robert Goldin, Daniela Moralli, Catherine M. Green, Chris J. Peters, Nagy Habib, Hani Gabra, Rebecca C. Fitzgerald, Zoltan Takats and George B. Hanna ()
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Stefan Antonowicz: Imperial College London
Zsolt Bodai: Imperial College London
Tom Wiggins: Imperial College London
Sheraz R. Markar: Imperial College London
Piers R. Boshier: Imperial College London
Yan Mei Goh: Imperial College London
Mina E. Adam: Imperial College London
Haonan Lu: Imperial College London
Hiromi Kudo: Imperial College London
Francesca Rosini: Imperial College London
Robert Goldin: Imperial College London
Daniela Moralli: University of Oxford
Catherine M. Green: University of Oxford
Chris J. Peters: Imperial College London
Nagy Habib: Imperial College London
Hani Gabra: Imperial College London
Rebecca C. Fitzgerald: University of Cambridge
Zoltan Takats: Imperial College London
George B. Hanna: Imperial College London

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21800-5

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DOI: 10.1038/s41467-021-21800-5

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