Oxidative DNA damage in Barrett mucosa: correlation with telomeric dysfunction and p53 mutation

Area of Science:

• Gastroenterology
• Molecular Biology
• Oncology

Background:

• Barrett esophagus arises from chronic inflammation and oxidative DNA damage.
• Eight-hydroxydeoxyguanosine (8-OHdG) is a key oxidative DNA adduct, with its repair capacity influenced by OGG1 polymorphism.
• Telomere length dynamics, influenced by oxidative stress and telomerase activity, are implicated in cellular senescence and immortalization, with limited data in Barrett esophagus.

Purpose of the Study:

• To investigate the relationship between 8-hydroxydeoxyguanosine (8-OHdG) levels, OGG1 polymorphism, telomerase activity, telomere length, and p53 mutations in the progression of Barrett esophagus.

Main Methods:

• Analysis of biopsy samples from 40 Barrett esophagus patients (short- and long-segment) and 20 controls.
• Measurement of 8-hydroxydeoxyguanosine (8-OHdG) levels, OGG1 polymorphism, telomerase activity, and telomere length.
• Serum analysis for p53 mutations.

Main Results:

• Controls exhibited lower 8-OHdG and telomerase activity, with normal telomeres and no p53 mutations.
• Short-segment Barrett esophagus showed elevated 8-OHdG, telomere shortening, and increased telomerase activity, without p53 mutations.
• Long-segment Barrett esophagus presented highest 8-OHdG levels, telomere elongation, and p53 mutations in 42% of patients.

Conclusions:

• Barrett esophagus progression is characterized by accumulating oxidative DNA damage.
• This damage induces telomere instability and telomerase activation.
• Late-stage progression involves p53 mutations, disrupting cell cycle control and promoting cancer development.