Journal article 118 views 13 downloads
Lymphocyte Micronucleus Formation Is Driven by Inflammation-Induced Oxidative DNA Damage in Oesophageal Cancer Development
,
Rachel Lawrence,
Hasan Haboubi,
Hamsa Naser,
Kate Hurlow,
Ume-kulsoom Shah ,
Lisa Williams,
Sarah Gwynne,
Owen Bodger ,
Jiri Zavadil,
Francois Virard,
shareen Doak,
Laura Thomas ,
Gareth Jenkins
International Journal of Cancer
Swansea University Authors:
Kathryn Munn , Hamsa Naser, Kate Hurlow, Ume-kulsoom Shah , Owen Bodger , shareen Doak, Laura Thomas , Gareth Jenkins
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DOI (Published version): 10.1002/ijc.70494
Abstract
We investigated mechanisms underlying circulating DNA damage across the gastro-oesophageal reflux disease (GORD), Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC) spectrum using the lymphocyte micronucleus (MN) assay. MN frequency (MN%) was quantified in lymphocytes from healthy v...
| Published in: | International Journal of Cancer |
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| ISSN: | 0020-7136 1097-0215 |
| Published: |
Wiley
2026
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa71742 |
| Abstract: |
We investigated mechanisms underlying circulating DNA damage across the gastro-oesophageal reflux disease (GORD), Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC) spectrum using the lymphocyte micronucleus (MN) assay. MN frequency (MN%) was quantified in lymphocytes from healthy volunteers (HVs), GORD, BO and OAC patients, alongside plasma biomarkers of inflammation and oxidative stress. Ex vivo challenge assays assessed lymphocyte responses to hydrogen peroxide (H2O2), vinblastine and the bile acid deoxycholic acid (DCA). Tissue-based NF-κB expression was also correlated with MN levels. OAC patients exhibited significantly elevated MN% compared with HVs (p < 0.001), GORD (p < 0.001) and BO (p = 0.016). OAC lymphocytes showed increased sensitivity to vinblastine relative to HVs (p = 0.025) and GORD patients (p = 0.033). Higher baseline MN% correlated with reduced inducible MN formation following H2O2 or DCA, suggesting altered oxidative stress responses. MN% also associated with plasma 8-OHdG, IL-8 and 2′3′-cGAMP, and with reduced oesophageal tissue IκB, indicating activation of oxidative and cGAS-STING/NF-κB signalling. These findings highlight systemic aneugenic and oxidative stress processes that contribute to lymphocyte MN formation in OAC and suggest that MN% may serve as a minimally invasive indicator of inflammation-linked genomic instability. Further investigation is needed to determine its relevance to OAC progression. |
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| Keywords: |
circulating biomarkers; DNA damage; micronucleus; oesophageal adenocarcinoma; oxidative stress |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
Cancer Research Wales |