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Epigenetic changes wipe out protective mechanisms in Barrett’s oesophagus
  1. Rebecca C Fitzgerald
  1. Dr Rebecca Fitzgerald, MRC Cancer Cell Unit, Hutchison-MRC Research Centre, Cambridge, CB22 0XZ; rcf{at}hutchison-mrc.cam.ac.uk

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Reactive oxygen and nitrogen species play important roles in the regulation of cell survival. The effects are dose dependent and consist of two stages: reversible redox regulation and irreversible oxidative molecular damage. The Barrett’s oesophageal epithelium is bathed in a hostile luminal environment comprising reflux and dietary components. Increasing evidence suggests that these factors lead to abnormal levels of oxidative stress in the metaplastic epithelium, thus setting the stage for dysplasia and adenocarcinoma14 Cancer might seem inevitable in the face of such insults but, due to a plethora of defence mechanisms, this outcome is usually avoided. Although the mechanisms by which higher organisms respond to elevated oxygen and nitrogen species in vivo is poorly understood, the endogenous antioxidases are a key mechanism through which our cells combat oxidative stress. Key enzyme families include the glutathione S-transferases and peroxidases, and the loci encoding these enzymes comprise large supergene families. The principle role of glutathione S-transferases is detoxification of endogenous and exogenous electrophiles by glutathione conjugation,5 whereas the glutathione peroxidases catalyse the reduction …

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